Combination-sensitive neurons in the medial geniculate body of the mustached bat: encoding of target range information.

1. Delay-tuned combination-sensitive neurons (FM-FM neurons) have been discovered in the dorsal and medial divisions of the medial geniculate body (MGB) of the mustached bat (Pteronotus parnellii). In this paper we present evidence for a thalamic origin for FM-FM neurons. Our examination of the response properties of FM-FM neurons indicates that the neural mechanism of delay-tuning depends on coincidence detection and involves an interaction between neural inhibition and excitation. 2. The biosonar pulse (P) and its echo (E) produced and heard by the mustached bat consist of four harmonics; each harmonic contains a constant frequency (CF) component and a frequency modulated (FM) component. Thus the pulse-echo pair contains eight CF components (PCF1-4, ECF1-4) and eight FM components (PFM1-4, EFM1-4). The stimuli used in this study consisted of CF, FM, and CF-FM sounds: paired CF-FM sounds were used to simulate any two harmonics of pulse-echo pairs. The responses of FM-FM neurons in the MGB were recorded extracellularly. We found that FM-FM neurons respond poorly or not at all to single sounds, respond strongly to paired sounds, and are tuned to the frequency and amplitude of each sound of the pair and to the time interval separating them (simulated echo delay). 3. All FM-FM neurons are facilitated by paired FM sounds and most are facilitated by paired CF sounds. Best facilitative frequencies measured with paired CF sounds fall outside the frequency ranges of the CF components of biosonar signals, whereas best facilitative frequencies measured with paired FM sounds fall within the frequency ranges of the FM components of biosonar signals. Thus FM-FM neurons are expected to respond selectively to combinations of FM components in biosonar signals. The FM components of pulse-echo pairs essential to facilitate FM-FM neurons are the FM component of the fundamental of the pulse (PFM1) in combination with the FM component of the second, third, or fourth harmonic of an echo (EFM2, EFM3, EFM4; collectively, EFMn). 4. The frequency combinations to which FM-FM neurons are tuned reflect small deviations from the harmonic relationship such as occurs in combinations of FM components from pulses and Doppler-shifted echoes. Compared with CF/CF neurons, however, FM-FM neurons are broadly tuned to stimulus frequency. Thus FM-FM neurons are Doppler-shift tolerant and relatively unspecialized for processing velocity information in the frequency domain.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vinyl polymerization with dimethylaniline/cupric nitrate system

A study of vinyl polymerizations initiated with the system of dimethylaniline (DMA) and cupric [Cu(II)] nitrate has been made. This initiator system was found to induce the polymerization of vinyl monomers having an electron-attracting substituent such as methyl methacrylate (MMA) and acrylonitrile, but it does not initiate the styrene and vinyl acetate polymerizations. The rate of polymerization (R_p) of MMA with this system was expressed by the following Eqs., depending upon the Cu(II) concentration used: The apparent activation energy for this polymerization was found to be 16.5 and 14.4 kcal/mole for the above two Cu(II) concn. ranges, respectively. The polymer of MMA obtained by this system was found to contain an endgroup similar to dimethylaniline, probably a methylanilinomethyl group, from the determination of its UV spectrum.     

An enzyme immunoassay for K-76 monocarboxylic acid, a novel anticomplementary compound

A competitive enzyme immunoassay for K-76 monocarboxylic acid (K-76COOH), a novel anticomplementary compound, was developed. K-76COOH was directly coupled with bovine serum albumin through a formation of Schiff base and successive reduction. The spectral data of the conjugate showed no evidence of a Schiff base form. Using the specific antiserum, the proposed homologous assay made it possible to detect K-76COOH at the lowest value of 1 ng/ml of plasma. The immunoassay was validated by the correlation with HPLC analyses. The time courses of plasma levels of K-76COOH after a single oral administration to beagle dogs were precisely determined with a very low absorption efficiency. From these results, it is suggested that the plasma values obtained are insufficient for K-76COOH to exert its anticomplementary action in vivo; thus K-76COOH may have another immunopharmacological function.     

Evaluation of the staining findings of immunofluorescence in unfixed or fixed renal biopsy specimens from patients with IgA nephropathy and membranous nephropathy

A study on the evaluation of staining findings of immunofluorescence in unfixed or fixed renal biopsy specimens is described. Renal biopsy specimens obtained from ten patients with IgA nephropathy and membranous nephropathy were embedded in gelatin or paraffin matrix. Renal biopsy specimens embedded in paraffin matrix were digested with 0.05% protease. The specimens were stained with FITC-conjugated anti-human IgA, IgG, IgM or C3 antisera at 4 degrees C overnight. IgA, IgG or IgM were markedly observed in glomeruli using unfixed materials embedded in gelatin matrix or 10% neutral buffered formalin fixed materials embedded in paraffin matrix from patients with IgA nephropathy and membranous nephropathy. There was no significant difference in the intensity or distribution of IgA, IgG or IgM deposition among the two different conditions of immunofluorescence in patients with such diseases. Although the deposition of IgA using unfixed materials embedded in gelatin matrix was prominently coarse granular or lumpy in glomeruli from patients with IgA nephropathy, that of IgA using 10% formalin fixed materials embedded in paraffin matrix was fine granular and/or interrupted linear in glomeruli. It was suggested that the immunofluorescence in renal biopsy specimens embedded in paraffin matrix after digestion with protease is useful for the evaluation of immunoglobulins in glomeruli from patients with IgA nephropathy or membranous nephropathy.     

Corticofugal amplification of facilitative auditory responses of subcortical combination-sensitive neurons in the mustached bat

Recent studies on the bat's auditory system indicate that the corticofugal system mediates a highly focused positive feedback to physiologically "matched" subcortical neurons, and widespread lateral inhibition to physiologically "unmatched" subcortical neurons, to adjust and improve information processing. These findings have solved the controversy in physiological data, accumulated since 1962, of corticofugal effects on subcortical auditory neurons: inhibitory, excitatory, or both (an inhibitory effect is much more frequent than an excitatory effect). In the mustached bat, Pteronotus parnellii parnellii, the inferior colliculus, medial geniculate body, and auditory cortex each have "FM-FM" neurons, which are "combination-sensitive" and are tuned to specific time delays (echo delays) of echo FM components from the FM components of an emitted biosonar pulse. FM-FM neurons are more complex in response properties than cortical neurons which primarily respond to single tones. In the present study, we found that inactivation of the entire FM-FM area in the cortex, including neurons both physiologically matched and unmatched with subcortical FM-FM neurons, on the average reduced the facilitative responses to paired FM sounds by 82% for thalamic FM-FM neurons and by 66% for collicular FM-FM neurons. The corticofugal influence on the facilitative responses of subcortical combination-sensitive neurons is much larger than that on the excitatory responses of subcortical neurons primarily responding to single tones. Therefore we propose the hypothesis that, in general, the processing of complex sounds by combination-sensitive neurons more heavily depends on the corticofugal system than that by single-tone sensitive neurons.     

Metal-containing initiator systems, 34. Polymerization of vinyl monomers initiated by the binary system cobaltocene/bis(ethyl acetoacetato)copper (II)

The effect of some metallocenes such as ferrocene (Fe(C₅H₅)₂), nickelocene (Ni(C₅H₅)₂), and cobaltocene (Co(C₅H₅)₂), on the vinyl polymerization initiated with bis(ethyl acetoacetato)-copper(II) (Cu(eacac)₂) was investigated. Co(C₅H₅)₂ was found to exert a markedly accelerating effect on the polymerization of methyl methacrylate (MMA) with Cu(eacac)₂. The polymerization of MMA with the system Co(C₅H₅)₂/Cu(eacac)₂ at 50°C was found to be fairly affected by the solvent used. The results of copolymerization of MMA with styrene (St) and the effect of hydroquinone (HQ) on the polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ showed that the polymerization proceeds via a radical mechanism. The polymerization of MMA with Co(C₅H₅)₂/Cu(eacac)₂ was studied kinetically in acetone. The overall activation energy of the polymerization was calculated to be 86,3 kJ/mol (20,6 kcal/mol). This value was somewhat higher than that (17,6 kcal/mol) obtained for the polymerization of MMA with Cu(eacac)₂ alone. The polymerization rate (R_p) is represented by the following equation: R_p = k[Co(C₅H₅)₂]^0,5 [Cu(eacac)₂]^0,2 [MMA]^1,3. The high order in monomer concentration suggests a participation of the monomer in the initiation process of this polymerization. This is supported by the examination of the ESR spectrum of the system Co(C₅H₅)₂/Cu(eacac)₂/MMA/acetone, where reduction of Cu(II) to Cu(I) occurs. To elucidate the initiation mechanism, the spin trapping technique was applied to the system Co(C₅H₅)₂/Cu(eacac)₂/methyl acrylate. From these results, an initiation mechanism for the binary initiator system Co(C₅H₅)₂/Cu(eacac)₂ is proposed and discussed.     

Multiple time axes for representation of echo delays in the auditory cortex of the mustached bat

The properties of the orientation sound (pulse) of the Jamaican mustached bat, Pteronotus parnellii parnellii is the same as the Panamanian mustached bat, P.p. rubiginosus. It consists of four harmonics, each containing a long constant-frequency (CF) component followed by a short frequency-modulated (FM) component. Thus, there are eight components in total: CF1-4 and FM1-4. The combination-sensitive area of the auditory cortex in P.p. parnellii consists of two major divisions (FM-FM and CF/CF areas) as in P.p. rubiginosus. The FM-FM area projects to the dorsal fringe (DF) and other areas. Response latencies of neurons in the DF area are longer than those in the FM-FM area. The distribution of latencies is unimodal for the FM-FM area, but bimodal for the DF area. In this electrophysiological study of the response properties of neurons in the DF and FM-FM areas, our aim was to find out how signal processing might be different between the two areas. Both the FM-FM and DF areas consist of three types of FM-FM combination-sensitive neurons: FM1-FM2, FM1-FM3, and FM1-FM4. They do not respond or respond poorly to pulse alone, echo alone, single CF tones or single FM sounds. But they show strong facilitation of response to the echo when it is delivered with particular delays from the pulse. The essential elements in the pulse-echo pair for facilitation are the FM1 of the pulse and FM2 or FM3 or FM4 of the echo. In both the FM-FM and DF areas, the great majority of neurons show short-lasting facilitation, and other neurons show long-lasting facilitation. FM-FM neurons are tuned to particular echo delays, i.e., target ranges. In both the FM-FM and DF areas, the width of a delay-tuning curve is linearly related to the value of a best delay. There is no sign that processing of range information is more specialized in the DF area than the FM-FM area. In both the FM-FM and DF areas, three types of FM-FM neurons form independent clusters. Along the major axis of each cluster, best delays for facilitative responses of neurons systematically change according to the loci of the neurons. The more posterior the location, the longer the best delay is. Therefore, there are six time (i.e., range) axes in total. The time axis in the DF area is shorter than that in the FM-FM area.(ABSTRACT TRUNCATED AT 400 WORDS)     

A new superselective balloon catheter--all-silicone catheter with a floppy tip

We have introduced concept of "chemical" embolization and have tried to develop a new agent which would enable us to embolize the lesion with one-shot injection. Such an agent must be able to occlude diffusely the lesion distal to the catheter. This has made it mandatory to develop a new catheter which can be introduced into the vessel as close to the lesion as possible with fewer risks of clot formation and/or vessel damage. A new superselective balloon catheter for angiography and infusion of liquid embolizing materials has been developed. This catheter consists of a proximal relatively stiff silicone catheter, a short distal thin-walled flexible silicone catheter and silicone balloon. These three silicone components are connected by silicone adhesives. The distal catheter allows us to catheterize fine arteries such as lenticulostriates, while the proximal catheter assures easy manipulation. This balloon catheter can be used for superselective angiography and infusion of liquid embolizing materials. It has been used on nine patients; one with a dural arterio-venous malformation (AVM), four with meningiomas, and four with brain and spinal cord AVMs. In the case of dural AVM and meningiomas, it was possible to easily introduce into the middle meningeal artery distal to the foramen spinosum. In addition, in one of the cases of meningioma, we were able to catheterize one of the main feeding pedicles beyond the pterion. Chemical embolization was carried out in 5 cases with good results. In the case of brain and spinal cord AVM, useful information was obtained from the superselective angiography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

Pig kidney xenotransplantation: Progress toward clinical trials

Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ‐source pigs has largely been directed to two major aims—(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement‐ and coagulation‐regulatory proteins. Conventional (FDA‐approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non‐immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait‐list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.