Increase In Initial Volume Research Articles

Pseudoprogression As Adverse Event of Chimeric Antigen Receptor T Cell Therapy

CAR-T-cell therapy (CARTCT) expands the range of therapeutic options for patients with hematologic malignancies. While complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well known, pseudoprogression (PP) is until now mainly described after checkpoint inhibition. Some reports on CARTCT induced PP (CARTiPP) exist distinguishing it from progressive disease, while only few reports focus on acute local complications. Considering the paucity of data about CARTiPP, we aimed to assess patients treated in our center. We defined CARTiPP as initial volume increase of malignant manifestations within ten days of CARTCT followed by tumor regression without another genesis being more probable. Distinction from true progression of malignancy can be achieved either retrospectively or by histopathological findings. Here, we characterize a retrospective monocentric patient cohort with the occurrence of CARTiPP. Evaluation of clinical, laboratory, radiological, and/or histopathological data was carried out. A total of n=8 patients were identified with CARTiPP throughout a treatment period of 46 months with n=78 patients receiving CARTCT resulting in a frequency of 10%. These eight patients had different B cell Non-Hodgkin lymphoma (B-NHL) subtypes (n=7) or multiple myeloma (n=1, extramedullary involvement) and were treated with anti-CD19 or anti-BCMA CAR-T-cells after standard lymphodepletion (once fludarabine monotherapy). The median age of patients was 61 years (range 39-76 years). Routine staging before CARTCT assessed n=4 patients as in partial remission (PR), n=1 with stable disease (SD) and n=3 with progressive disease (PD). CARTiPP occurred at a median of 5 days (range 4-7 days) after CARTCT. CAR T-cell expansion measured via droplet digital polymerase chain reaction (ddPCR) peaked earlier than expected from literature data after an average of 8 days post-infusion (range 7-11 days) in patients experiencing PP with a median peak of 182 CAR T copies/µL (range 39-2812 copies/µL) at this time. We observed variable complications, e.g. superior vena cava syndrome, postrenal kidney injury and compartment syndrome. The analogy in clinical CARTiPP presentation with previous symptoms in stages of further advanced disease was striking in most patients (n=6). All events were rated as adverse events ≥ CTCAE II (Common Terminology Criteria of Adverse Events). CRS occurred parallely with PP in n=7, ICANS in n=3 patients. Complication management ranged accordingly from intensified monitoring to treatment with glucocorticoids/tocilizumab to limb amputation in one patient.There was no CARTiPP-associated mortality. In one of the affected cases intensive care treatment was required due to complications other than CARTiPP. CARTiPP may be still underreported. Frequency and in some cases severity underline the need for raising awareness of treating physicians. Laboratory analyses and imaging may supplement clinical assessment and should be further examined. The establishment of risk assessment, preventive measures and early detection to reduce therapy-induced morbidity as well as a systematic documentation analogous to CRS and ICANS might be required for CARTiPP. The increasing availability of corresponding CAR-T-cell therapies for a steadily expanding number of disease entities with variable manifestations and different disease stages makes an increasing frequency of CARTiPP plausible.

Parametric Study on the Evaporation Characteristics of Biodiesel-Diesel-Methanol Microemulsion Droplets

ABSTRACT In order to investigate the evaporation characteristics of biodiesel-diesel-methanol microemulsions, an experimental method of droplet evaporation with post processing techniques is established. The droplet normalized square diameter (NSD), droplet temperature and images during evaporation process are used to analyze the evaporation characteristics at different ambient temperatures. The results indicate that the methanol volume percentage, initial volume of droplet and ambient temperature have evident influence on the evaporation characteristics of droplets. When the initial volume of droplet is 0.5 μL, BD95M5 (biodiesel-diesel blend (95%)+methanol (5%)) and BD85M15 (biodiesel-diesel blend (85%)+methanol (15%)) droplets do not show the puffing and micro-explosion phenomena during evaporation process, but BD75M25 (biodiesel-diesel blend (75%)+methanol (25%)) droplet exhibits micro-explosion evidently at ambient temperature of 573K. Puffing is observed for BD85M15 droplet, and micro-explosion is for BD75M25 droplet at ambient temperature of 773K. The droplet lifetime is decreased and the mean evaporation rate (MER) is increased with the increase of ambient temperature and methanol volume percentage in microemulsion. The evaporation process ends at 5.938 s/mm2, 5.417 s/mm2 and 4.792 s/mm2 for BD95M5, BD85M15 and BD75M25, respectively, and MERs of them are 0.087 mm3/s, 0.095 mm3/s and 0.108 mm3/s at ambient temperature of 573K. The MERs of BD95M5, BD85M15 and BD75M25 are 0.225 mm3/s, 0.244 mm3/s and 0.309 mm3/s, respectively, at ambient temperature of 773K. With the increase of initial volume of droplet, the occurrence of puffing and micro-explosion is strengthened. The MER of droplets with initial volume of 0.6 μL is the largest, which increases by 13.1% and 12.8% compared with 0.4 μL droplets and 0.5 μL droplets, respectively.

Experimental evidence of hydrogen evolution from local anodic corrosion sites and its consequences for corrosion cracking mechanisms

Abstract Based on observation of gas bubbles evolving from crevices on slow strain rate test pieces during anodic corrosion the effect of applied potentials in chloride aqueous solutions on amount and composition of the gas together with fracture strains from the slow strain rate test of a 17-4 PH steel was investigated. As a result, increasing applied potentials provide a reduction of fracture strains together with an initial increase in volume of released hydrogen gas. The fracture surfaces exhibit increasing brittle appearance, as found in hydrogen cracking failures. The results confirm that during local anodic corrosion, hydrogen is produced that provokes hydrogen induced cracking following anodic dissolution. Respective local pH measurements under varying applied electric potentials, show the acidification of the pit-electrolyte. Additional model calculations elucidate the stepwise local anodic corrosion and its acidification process together with the hydrogen supported cracking. The model shows that the relative amount of hydrogen cracking will depend on the provided material data as well as on solution properties such as pH, chloride level, temperature and oxygen content. As an all over result, together with the model calculations, the experimental evidence of hydrogen evolution during anodic local corrosion confirms the contribution of hydrogen cracking to anodic stress corrosion cracking.

Regionally specific changes in the hippocampal circuitry accompany progression of cerebrospinal fluid biomarkers in preclinical Alzheimer's disease.

Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) ɛ4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

Quantitative Correlation Between Hyaluronic Acid Filler and Hyaluronidase.

The hyaluronic acid-based filler (HA filler) is used worldwide in various applications. In particular, the HA filler is used in the plastics and cosmetic medical field for facial rejuvenation and contouring. In this setting, it is injected into the skin or underlying tissue. Complications of HA filler injection have been relieved using hyaluronidase. However, there is no standard dose to adjust for undesirable HA filler lumpness. In this study, the authors tried to analyze any quantitative correlation between HA filler and hyaluronidase. The back of each rat (total 14 rats) was divided into 4 sites. A volume of 0.5 mL HA filler was injected into the subdermal layer at each site and HA filler nodules were created on the dorsum of each rat. Each nodule was allocated to groups 1, 2, 3, and 4 according to the different concentrations of hyaluronidase. As a result, the injected HA filler volume doubled within 4 days of injection, and then decreased slowly thereafter in group 1 (control group with normal saline only). A 30 unit hyaluronidase treatment compensated for the initial volume increase (approximately 30%) with HA filler (0.5 ml) at the fourth day. Sixty units of hyaluronidase reduced the initial volume (0.5 mL) of overinjected or misplaced HA filler on the fourth day. Approximately 90 units of hyaluronidase can reduce to the volume by 0.25 mL (50%) of the injected HA filler on the fourth day. The authors believe that this quantitative analysis of hyaluronidase concentration is helpful to plan the amount of hyaluronidase for correction of HA filler injection errors.

MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation

ObjectivesTo assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence.MethodsQualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months.ResultsPost-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease (p < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT.ConclusionThe most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome.Key Points• This study describes imaging characteristics after irreversible electroporation (IRE) for pancreatic adenocarcinoma.• Familiarity with typical post-IRE imaging characteristics helps to interpret ablation zones.• Post-IRE, no central and variable rim enhancement are visible on contrast-enhanced imaging.• DWI-b800 may prove useful to predict early tumour recurrence.• Post-IRE examinations reveal an initial volume increase followed by a decrease.

The Effect of Therapeutic Whirlpool and Hot Packs on Hand Volume During Rehabilitation After Distal Radius Fracture: A Blinded Randomized Controlled Trial.

Edema is a possibility with all heating modalities due to the increase in local blood flow caused by vasodilation. Despite the frequent application of superficial heat modalities, their relative effect on hand volume has not been determined for the upper extremity. The objective of this study was to compare the immediate effects of hot packs and whirlpool on hand volume for patients with distal radius fracture (DRF) and to determine whether any changes in volume between these modalities were still present 30 minutes after heat application. Finally, to determine whether there were any differences in volume change between groups after 3 repeated therapy visits. Sixty patients with clinically healed DRFs were divided into 2 groups. Half received therapeutic whirlpool at each therapy visit, and the other half received a moist hot pack treatment for 3 consecutive visits. Hand volume was measured before heat, after heat, and at the end of each 30-minute therapy session. There was a significant difference between groups immediately after heat application, as patients in the whirlpool group experienced an initial volume increase greater than those who received a hot pack. When remeasured after a hand therapy session approximately 30 minutes later, this group difference in volume change was no longer significant. The overall change in volume from enrollment in the study to completion of the study 3 weeks later was not statistically different between groups. Whirlpool is a potential consideration when selecting a heat modality for patients with DRF.

Nonlinear cerebral atrophy patterns across the Alzheimer's disease continuum: impact of APOE4 genotype

The progression of Alzheimer's disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subject's level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele.

Structural stability and fission product behaviour in U3Si

The crystalline and amorphous structures of U3Si have been investigated using density functional theory techniques for the first time. The effects of disorder and the impact of fission products has been separated to understand the swelling characteristics of U3Si in both crystalline and amorphous U3Si. Initially, the stability of the three experimentally observed polymorphs of U3Si were explored. Subsequently, we modelled the amorphous U3Si system and conclude that initial increase in volume observed experimentally at low temperature corresponds well with the volume change that occurs with the observed amorphisation of the material. The solubility of Xe and Zr into both the crystalline and amorphous systems was subsequently investigated.

Gross tumour volume variations in primary non-small-cell lung cancer during the course of treatment with stereotactic body radiation therapy

We aim to quantify the variations in the gross tumour volume (GTV) during a course of stereotactic body radiotherapy (SBRT) and determine its impact on dosimetric coverage of the GTV. The GTVs and dose coverage for 14 patients with 16 primary non-small-cell lung tumours treated with SBRT were investigated. Initial GTVs were calculated from treatment planning CT scans. The prescribed doses ranged from 48 to 60 Gy in three to five fractions. Before each treatment, patients underwent a CBCT scan. For each CBCT scan, the GTV and the dose received by the GTV were determined and followed during the course of therapy. There was considerable variation in the measured GTVs during the course of therapy. Increases of up to 63.3% of volume measured by initial CBCT were detected during the first few fractions, after which GTV tended to decrease. Dose coverage (V95) for any given fraction deviated no more than 5% from optimised coverage obtained in the initial treatment plan. In the long term, all patients with follow-up scans demonstrated tumour shrinkage with no radiographic evidence of tumour recurrence. GTV, as evaluated in this study, demonstrates an initial increase in volume followed by a subsequent decrease. This volume change needs to be considered in the design of treatment plans and assignment of treatment margins.

Unit cell expansion in Laves phase‐type compounds caused by interstitial hydrogen

AbstractThe Laves phase‐type compounds of yttrium and rare earths with manganese (RMn2) easily absorb hydrogen which locates at the interstitial sites. It is well known that the lattice expands with increasing hydrogen concentration and the volume increases up to about 30%. The increase of the unit volume is nonlinear as a function of hydrogen content. To explain this behaviour a model in which the volume changes were correlated with the changes of the bulk modulus with hydrogen concentration was proposed by Hirata and co‐workers. This model describes properly the initial volume increase, but does not reflect the changes at higher concentrations. For the hydrides with R = Y, Gd, Er, Dy, Tb, Ho at x ≈ 3 the volume of AB3 interstitials becomes large enough for hydrogen to enter. According to this observation we extended this model. We show that the calculated volume expansion fits very well to the experimental data for RMn2 (R = Y, Gd, Dy, Tb, Ho). (© 2007 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

Prostatic edema in permanent prostate implants: Dynamical dosimetry taking volume changes into account

The purpose of this study is to determine the impact of edema on the dose delivered to the target volume. An evaluation of the edema characteristics was first made, and then a dynamical dosimetry algorithm was developed and used to compare its results to a standard clinical (static) dosimetry. Source positions and prostate contours extracted from 66 clinical cases on images taken at different points in time (planning, implant day, post-implant evaluation) were used, via the mean interseed distance, to characterize edema [initial increase (deltar0), half-life (tau)]. An algorithm was developed to take into account the edema by summing a time series of dose-volume histograms (DVHs) with a weight based on the fraction of the dose delivered during the time interval considered. The algorithm was then used to evaluate the impact of edema on the dosimetry of permanent implants by comparing its results to those of a standard clinical dosimetry. The volumetric study yielded results as follows: the initial prostate volume increase was found to be 1.58 (ranging from 1.15 to 2.48) and the edema half-life, approximately 30 days (range: 3 to 170 days). The dosimetric differences in D90 observed between the dynamic dosimetry and the clinical one for a single case were up to 15 Gy and depended on the edema half-life and the initial volume increase. The average edema half-life, 30 days, is about 3 times longer than the previously reported 9 days. Dosimetric differences up to 10% of the prescription dose are observed, which can lead to differences in the quality assertion of an implant. The study of individual patient edema resorption with time might be necessary to extract meaningful clinical correlation or biological parameters in permanent implants.

Guest sorption and desorption in the metal-organic framework [Co(INA)(2)] (INA=isonicotinate)--evidence of intermediate phases during desorption.

The metal-organic framework [Co(INA)(2)]x0.5EtOH (INA = isonicotinate, NC(5)H(4)-4-CO(2)(-)), was synthesised under solvothermal conditions. Its X-ray crystal structure shows channels containing ethanol guests which are hydrogen-bonded to carboxylate oxygens of the framework. The pyridyl rings of the framework alternate between 'open' and 'closed' positions along the channels resulting in large variation in the channel cross-sectional area from ca. 1.4 by 2.3 A at the narrowest point to 4.9 by 5.3 A at the widest. Despite the very small windows, the ethanol guests (of van der Waals diameter ca. 4.2-6.1 A) may be reversibly desorbed and sorbed into the structure quantitatively, as shown by in situ variable-temperture IR spectroscopy and XRPD. The single-crystal structure of the desolvated form [Co(INA)(2)] shows that there is no change in the overall connectivity on desolvation, but the rotational positions of the pyridine rings are altered. This suggests that pyridyl rotation may occur to allow guests to pass in and out. When the synthesis was conducted in 1-propanol solvent [Co(INA)(2)]x0.5Pr(n)OHxH(2)O, was obtained, and a single-crystal X-ray structure revealed the same overall connectivity as in but with pyridine rings disordered over closed and open positions. There was no evidence of included guests from X-ray crystallography, suggesting that they are also highly disordered. Variable-temperature XRPD performed on bulk samples showed peaks which were unsymmetrical and exhibited shoulders, suggesting that for each pattern obtained the material actually consisted of several closely-related phases. The movements of the peaks during desolvation showed the presence of intermediate phases before the final desolvated product was formed. The peak positions of the intermediate phases matched more closely with the calculated pattern for than with or, suggesting that they may have disordered structures similar to. The results also suggest that the intermediate phase represents an initial increase in volume before a larger decrease in volume occurs to give the final desolvated material.

A model study of the sea level variations in the Gulf of Riga and the Väinameri Sea

A high-resolution (of order 1 km grid) 2D hydrodynamic model is used to examine the water level in two nearly tideless semi-enclosed sub-basins of the Baltic Sea. The model is forced by the spatially homogeneous wind stress above the study area, the sea level fluctuations along the open boundaries and the river runoff into the basin. Based on the input and verification data from 1999, the water level and flow dynamics are reproduced, also, the dependence of the sea level variations from different forcing and morphometrical factors is investigated using idealistic forcing schemes. Comparison with the field data proved that the model is applicable for the development of an operational system for predicting extreme sea levels, focusing on low-level events in the Väinameri Sea and storm surges in the Pärnu Bay. While the low-level events associated with continuous eastern winds are mainly determined by the regional wind field over the Baltic Sea and Scandinavia, the storm surges are short-term and local. Very high sea levels (up to 253 cm in Pärnu) appear in combination with several factors, including a very strong (25−30 m s −1) SW or W wind as the most important one. The level grows due to the initial volume increase in the Baltic Sea, then, due to an additional volume increase in the Gulf of Riga, and finally, due to the local level slope and long wave rise effect in the narrow and tapering bays or channels. In the Pärnu Bay an amplitude growth due to the resonance in accordance with the barotropic 5 h seiche period of the Gulf of Riga is possible.

Pharmacokinetic parameters of vancomycin for therapeutic regimens in neutropenic adult patients

Vancomycin (V) is widely used in neutropenic patients, though its kinetics are known in this type of patient. In the present study, ten patients were included: all of them received an intensive therapy for non-Hodgkin malignant lymphoma, Hodgkin disease, myeloma, acute leukemia, followed by an autologous bone marrow transplantation in 6 cases. All patients were neutropenic (100/mm 3). The pharmacokinetic study was done at the first V administration: 1000 mg V were injected as a 1-h infusion. Plasma V concentrations were measured by an enzyme immunoassay (EMIT®, Syva, France). V maximal and minimal concentrations were 61.3 ± 38.6 μg/ml and 1.69 ± 0.77 μg/ml, respectively. Total V clearance was 158 ± 51 ml/min, with a creatinine clearance of 141.2 ± 36.2 ml/min on test day. V plasma kinetics can be described by a biexponential model, with the following parameters: V dα ( I) V dβ ( I) T 1 2 β ( h) T 1 2 β ( h) , 22.9±11.4 39.1±12.2 0.39±0.33 2.94±0.84 These data show a 3-fold increase of initial volume of distribution and a shortened (3-fold) T 1 2 β , if compared to values obtained in normal subjects. Because the bactericidal effect is time dependent, there can be a risk of insufficient antibiotic effect throughout the day. Our data suggest that new therapeutic regimens are needed for these patients.

Activation of adenylate cyclase during swelling of S49 cells in hypotonic medium is not involved in subsequent volume regulation.

Experiments in S49 mouse lymphoma cells indicate that adenylate cyclase activity is increased following swelling in hypotonic medium through a mechanism independent of the G-proteins which are involved in hormonal regulation of the enzyme. An intact actin cytoskeleton is apparently required for stimulation of adenylate cyclase by mechanical forces. It was hypothesized that this increase in cAMP may be involved in triggering subsequent volume regulatory events. Manipulation of intracellular cAMP content and protein kinase A activity in S49 cells prior to swelling or during the regulatory volume decrease following swelling provided no evidence of a significant role for cAMP in regulating the extent of initial volume increase or the subsequent regulatory volume decrease. Treatment of S49 cells with 10-200 microM miconazole, previously shown to inhibit adenylate cyclase activity, attenuated the initial volume increase with medium dilution and accelerated the rate of regulatory decrease in a dose-dependent and time-dependent manner. However, incubation with 100 microM miconazole for 20 min, which completely inhibited swelling-induced increases in cAMP content, had no significant effect on either the initial volume expansion or the extent of regulatory volume decrease.

Experimental Study on Consolidation of Marine Clays in Alternating Electric Current Field

ABSTRACT From microscopic point of view, consolidation of clays takes place when the driving forces for pore water flow exceed the forces tending to hold the water to clay particles. To consolidate soft clays, theoretically two ways can be considered. One is to enhance the driving forces for pore water flow and the other is to reduce temporarily the forces tending to hold the water. While conventional methods for consolidation are based on the former way, this paper deals with the latter idea by making use of electro-chemical properties of clay soils. In order to reduce the forces tending to hold pore water, an electrical disturbance was imposed to clays by loading alternating electric current (AC). A series of consolidation tests of marine clays under AC field were carried out. It is found that the consolidation of clays can take place by the loading of AC whose magnitude is larger than a critical value. In AC consolidation, the initial swelling and the subsequent consolidation was observed. The initial volume increase is considered to be an unique characteristic of the AC consolidation.

Autonomic control of penile erection in the dog.

1. In anaesthetized dogs, resting mean penile artery pressure (p.a.p.) and corpus cavernosum pressure (c.c.p.) were 70-100% and 10-15% of mean systemic blood pressure, respectively. 2. Stimulation of the pelvic nerve at 10 Hz produced an immediate drop in p.a.p. and c.c.p., followed 10-30 s later by a rise in c.c.p. to the level of p.a.p. This level was 60-90% of systemic pressure, and was maintained throughout stimulation. 3. The threshold for a rise in c.c.p. was 3-5 Hz. Atropine (1 mg/kg), phentolamine (200 micrograms kg-1) and propranolol (200 micrograms kg-1) had no effect on the response to pelvic nerve stimulation. 4. C.c.p., p.a.p. and their changes in response to pelvic nerve stimulation were not significantly altered by either stimulation or section of the hypogastric nerves. 5. Cutting the sympathetic chain on both sides at L5, or administration of phentolamine, had no effect on resting c.c.p. or p.a.p. However, subsequent responses to pelvic nerve stimulation were enhanced. 6. When the pelvic nerve was stimulated during excitation of the sympathetic chain, there was still an initial drop in p.a.p. and c.c.p. but the subsequent increase in c.c.p. was delayed or abolished. These effects were mimicked by close arterial injection of phenylephrine and blocked by alpha-adrenergic antagonists. 7. This study suggests that erections in response to pelvic nerve stimulation result from an initial increase in volume of the corpus spongiosum, followed 20 s later by a stiffening of the corpus cavernosum as its pressure increases. Only the latter process is inhibited by activity of the sympathetic fibres.

MORPHOGENENSIS OF THE CARPOPHORE OF COPRINUS CINEREUS

SummaryAn interpretation of carpophore morphogenesis is presented which is derived both from the literature and from original observations. Cultured material of Coprinus cinereus (also called C. macrorhizus and C. lagopus) has been studied using biochemical assays together with light‐, scanning‐ and transmission electron microscopy to provide details of histology and the levels and distribution of protein, glycogen and NADP‐linked glutamate dehydrogenase during the course of development of stipe and cap. Initially, aggregates of hyphae form primordia which subsequently develop into mature carpophores. During stipe development glycogen deposition is at first restricted to cells forming a cup‐shaped mass in the stipe base, but very early in primordium development this deposit is depleted and glycogen accumulates in the gills, particularly the subhymenium, where it probably serves as a reserve material for the later stages of cap development. The distribution of cytochemically detectable protein differs from that of glycogen in that the former initially accumulates in the upper regions of the primordial stipe and in the gill hymenium. The stipe showed no conspicuous change in its content of protein during development although in the cap the fraction of the dry wt represented by protein increased substantially. Primordial stipes are composed of overlapping cells of hyphal dimensions with dense cytoplasm and small vacuoles. Stipe development depends on cell enlargement, this seeming to be biphasic; an initial increase in volume being attributable to an increase in cell diameter to give an undifferentiated dikaryotic central region and a differentiated multi‐nucleate cortex. Stipe growth depends on reallocation of cellular components, no one reserve material being identifiable as of prime importance although a few simple sugars do appear to be correlated with the osmoregulatory activity connected with the large scale uptake of water involved in stipe elongation. In the primordium cap the subhymenium is an open tissue of interwoven hyphae, the cells containing large accumulations of glycogen. The hymenium is formed from dikaryotic branches of the subhymenial hyphae to become an organised layer of hyphal tips. Subsequently, although the subhymenial hyphae remain as such, the hymenial cells become inflated. The paraphyses come to form a pavement of appressed and interlocked cells each containing a large central vacuole. Basidia are only slightly enlarged and contain dense cytoplasm with few vacuoles; they contrast with the much extended and inflated cystidia. Despite their inflation, all three cell types still show continuity with the subhymenial hyphae. During cap expansion the major inflationary force is paraphyseal enlargement but as the gill lamellae are removed by autodigestion fürther cell inflation in the pileal flesh enables it to assume a supportive role. In the earlier stages there is some correlation between declining glycogen content of the cap and increasing activity of NADP‐linked glutamate dehydrogenase. It is suggested that cap expansion is driven osmotically and that at least some of the osmotically active materials are synthesised through the urea cycle. At first this activity could be supported by glycogenolysis and amination but later on substrates may be provided by autodigestion of spent gill tissues. It is concluded that cap development is regulated by a metabolism quite distinct from those of either the parental mycelium or the stipe, and that the fundamental metabolic changes occurring throughout carpophore development are orchestrated by light. As carbohydrate nutrients in the medium approach exhaustion suppression of mycelial morphogenesis into hyphal aggregates is lifted, but the subsequent switch from the vegetative pathway of sclerotium development to carpophore formation is normally dependent on illumination with low intensity blue light. Growth then becomes polarized to form a presumptive pileus and glycogen is mobilized from the surrounding mycelium to accumulate at the base of the stipe. Receipt of a second illumination inhibits fürther growth of the stipe base and causes glycogen reserves to be translocated to the cap. Glycogen is utilized in the cap to produce glycolytic intermediates, allowing regulation of many aspects of metabolism by catabolite concentration and contributiong to the diverse syntheses required for spore formation and dissemination.

Effect of movement and external pressure on the vascular tone of the fingers.

Abstract 1. Finger plethysmograms were recorded during passive and active movements and pressure in vola manus and planta pedis, and on the muscles of the upper and lower leg. 2. They showed a rapidly occurring and passing volume change of the digit. 3. Some movements were characterized by an initial increase in volume, some by a decrease. On ceasing the movement or releasing the pressure there was a recoil to the opposite reaction. 4. Spontaneous variations of the responses were observed and different fingers sometimes reacted differently. 5. The reaction was also obtained peripheral to an obstruction of the circulation. 6. It is proposed that the observed effects are due to vasomotor reflexes produced by the stimulation of stretch receptors in the locomotion system.