Reliability of the contingent negative variation and the auditory evoked potential. Contingent negative variations (CNVs) composed of 32 trials had a median subject consistency of 0.68 in retests separated from 5 min to 7 days. Hand measurement of the CNV was highly reliable with a median reliability of 0.96. Subject consistencies for the amplitudes and latencies of N1 and P2 components of a auditory evoked potential (AEP) had a median of 0.59 when 265 trials were averaged. These consistencies for N1 and P3 components had a median of 0.45 when only 16 trials were averaged. Median measurement reliabilities for the AEP were 0.92 for amplitudes and 0.66 for latencies.


A simulation study of the efficacy of stepwise discriminant analysis in the detection and comparison of event related potentials. Cortical average evoked potentials were simulated by summing five damped sinusoids. The characteristics of these "evoked" responses could be manipulated by changing parameters of the sinusoids. The synthesized signals were mixed with noise processes whose power and band-width were manipulated. Thus data were generated to stimulate a variety of conditions which could conceivably occur in an experiment on evoked potentials. Stepwise discriminant analysis (BMD07M) has been applied to these simulated data in an attempt to determine the degree to which the program identifies, in a sensible manner, the differences we introduced into the synthesized evoked responses. The simulation results indicate that stepwise discriminant analysis can indeed be an efficacious tool in research on evoked potentials. The program does detect differences in evoked potentials. It can be used, with some reservations, to identify the components of an evoked potential which the experimental variables have affected. In a special set of simulations we have attempted to determine the degree to which stepwise discriminant analysis could serve to detect the presence or absence of an evoked potential. These simulations show that the score of an average evoked potential in the data. The implications of this finding to the use of evoked potentials in sensory sensitivity testing were evaluated in studies for the effect on them of stimulus intensity.


On the relation between the EMG frequency spectrum and the duration of symptoms in lesions of the peripheral motor neuron. Two samples of muscles, one with proved, the other with doubtful neurogenic lesions have been investigated with EMG frequency analysis. Confirming reports from previous authors it was possible to show that a large proportion of muscles with proved lesions have a displacement of the frequency spectrum towards low frequencies("bass" displacement). The displacements were principally found in cases with old lesions. In a group of cases in which the symptoms had lasted a few months only a displacement towards high frequencies ("descant" displacement) was revealed. In view of these findings it was surprising to note a relatively large number of spectra with bass displacement in a group of cases in which the symptoms had lasted less than one month. The probable explanation of this is to be found in the fact that the muscles with bass displacement in this group principally belonged to patients with systemic diseases such as diabetes, alcoholism, renal insufficiency, itc., who quite possibly might have had earlier neurogenic lesions with a subclinical course. In the group of muscles with doubtful neurogenic lesions there was also found a comparatively large number of bass-displaced spectra. It was possible to show that here also there was a large number of patients with systemic diseases.


Visual evaluation and computer analysis of the EEG--a comparison. Spectral parameter analysis (SPA) of the EEG provides a description of the distribution of spectral power in the EEG signal in the form of a rational spectrum with not more than 8 parameters. The spectrum is divided into 1-3 components described by frequency and power parameters: bandwidth (delta), peak frequency (f) and power (G). These spectral parameters are determined with the aid of a computer. The character of the EEG signal decides whether 1, 2 or 3 components (delta, alpha, beta) are needed to describe the spectrum. To test its practical value, the result of SPA was compared with that of ordinary visual evaluation of the EEG of 65 healthy men between the ages of 18 and 22 years. 20 sec sections from different leads were analysed and evaluated visually. Each EEG section was graded according to the amount of visually evaluated slow activity (VESA). To investigate the relation between the degree of VESA and the SPA result, statistical calculations (variance and regression analyses) were carried out, both for single SPA parameters and for the general type of spectrum, i.e., the number of components composing the spectrum. The SPA results from sections with artefacts were treated separately and compared statistically with results from artefact-free sections. In records with a high degree of VESA, all the leads analysed showed a tendency to have a power spectrum of low order, i.e., with few components. In most leads there was a linear regression between the degree of VESA and the bandwidth and power of the delta and alpha components. In several cases this relation was an expression of a significant linear change of the SPA parameter as a function of the degree of VESA. On the other hand the parameters of the beta component showed no relation to the degree of VESA. It was found that muscle activity could influence any spectral component thereby providing it with a strongly increased bandwidth. This is probably due to the fact that muscle activity resembles white noise in this particular frequency range. Low frequency artefacts affected only the delta component the bandwidth of which was significantly smaller than in the artefact-free sections.


An electronic activity integrator for operant conditioning of patterns of neural and muscular activity. An activity integrator circuit designed to detect and operantly reinforce patterns of neural and muscular activity is described. An integrator voltage proportional to the weighted sum of multiple input signals reaches a threshold level when the requisite response pattern is emitted. A variety of response patterns may be differentially reinforced, depending on the nature of the integrated signals.


Frequency dependence of the transmission of the EEG from cortex to scalp. Simultaneous recordings of the EEG at subdural and scalp electrodes often show very different activities. Large amplitude activity with maximum power between 15 and 30 c/sec can be often observed on the subdural electrodes together with smaller amplitude lower frequencies, whereas on the scalp only a small part of this high frequency activity is seen and the lower frequencies dominate. The impedance between cortex and scalp has been shown to be similar for low and high EEG frequencies and the high attenuation of the beta activity at scalp electrodes is believed to be due to summation of polyphasic cortical activity. The weighted summation of this polyphasic activity across a limited cortical area (spatial average) is similar to the activity of a non-recursive filter between cortex and scalp and has a low pass characteristic.


Localization of immunoreactive androgen in testicular tissue. Immunohistochemical localization of androgen in the testes of both rat and squirrel monkey has been performed using an antiserum specific to testosterone and certain related androgens. The bound antibodies were visualized by coupling with antigammaglobulin labeled either with fluorescein isothiocyanate or with a horseradish peroxidase-diaminobenzidine technique. The highest concentration of androgen was found in the interstitial tissue but a significant amount was also present in the seminiferous tubules in the layer adjacent to the tubular wall. Very small amounts of androgen were localized in the tubular wall. This restricted localization in the tubules might indicate either de novo synthesis or active uptake of steroids intermediate in the biosynthesis of testosterone in the seminiferous tubules.


Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). The clinical symptomatology of the Zollinger-Ellison syndrome and the pathologic anatomy of gastrinomas are reviewed. Experience with 17 patients with the Zollinger-Ellison syndrome is presented with special reference to stimulation tests (secretin, glucagon, calcium infusion, test meal) and to localization and immunohistologic, ultrastructural, and biochemical findings in gastrinomas. Multiple hormone production by the tumors is frequent. The ultrastructure and the Sephadex G-50 gel filtration patterns of immunoreactive gastrin in sera and tumors are not uniform and are not related to localization of the tumors in the pancreas or duodenum or to the gastrin concentration. Hyperplasia of the pancreatic islets is a frequent finding in gastrinoma patients, suggesting that hypergastrinemia may stimulate islet growth.


Recurrent granular corneal dystrophy.

Recurrent granular corneal dystrophy. Four full-thickness corneal buttons and tissue from one lamellar keratoplasty, derived from four patients with granular corneal dystrophy recurring in previously transplanted corneas, were studied by light and transmission electron microscopy. Fibrous tissue without vascularization was present between the epithelium and Bowman's membrane and contained deposits characteristic of granular dystrophy in both light and electron microscopy. The recurrence of dystrophy in the normal donor cornea is the result of infiltration of the grafted cornea by host invasion. The donor stroma is spared.


Significance of cellular interactions in the immune response. Recent investigations relevant to T and B cell cooperation in humoral immunity are discussed from the following aspects: requirement for T cells in antibody responses; T cell facilitation of B cell responsiveness; T cell suppression of B cell responsiveness; evidence for a nonspecific influence of T cells on B cell responsiveness; relevance to clinical disorders.


Maximal rise in IgE antibody following ragweed pollination season. Patients allergic to ragweed pollen who did not receive immunotherapy had an increase in ragweed-specific IgE antibodies associated with seasonal exposure. Of 17 such patients, 15 reached peak levels between mid-September and mid-October. Two had peak values after mid-October; the levels were only slightly higher than earlier values. Our study shows that serum obtained in mid-October reflects approximately the maximal IgE antibody level attained 0y ragweed-sensitive patients in our area and that this value can be used as a baseline in monitoring the subsequent decline in antibodies. In addition, our data support an earlier observation that the magnitude of seasonal rise in IgE antibody is related to the preseasonal value. The significantly positive correlation of the results of carefully performed skin tests (end point titration) with radioallergosorbent test (RAST) values suggests the possibility that the RAST can be employed as a reliable diagnostic aid, perhaps even replacing the skin test.


Arteriosclerotic changes within the diabetic oral vasculature. Microscopic sections of diabetic, arteriosclerotic nondiabetic, and nondiabetic nonarteriosclerotic human palate were qualitatively evaluated for small artery colloidal-iron-positive, acid mucopolysaccharide content. The association of abnormal colloidal-iron-positive material with structural detail in the arterial wall was clarified by comparison with specimens of amputated diabetic human legs.


A selective inhibitor of the elicitation of immune-mediated reactions. 6-Chloro-17 alpha-hydroxypregna-1,4,6-triene-3,20-dione (CHP), a steroid having a progestin-type structure yet not having progestational activity, was found to exhibit moderate anti-inflammatory activity in a number of conventional tests for corticoid potency (e.g., thymolytic, granuloma, carrageenin edema). CHP was essentially equipotent, however, with cortisol in models of inflammation mediated via delayed hypersensitivity such as experimental allergic encephalomyelitis, adjuvant-induced arthritis, mouse skin graft, and mouse skin delayed hypersensitivity. In contrast to cortisol, which inhibits both 19-s and 7-s antibody formation, CHP does not diminish the number of cells producing either antibody.


Glycocalyx of epidermal cells in vitro: demonstration and enzymatic removal. Guinea-pig epidermal cells in culture possess a glycocalyx coat similar to that in vivo, as revealed by the ruthenium red stating technique. Trypsin, phospholipase C, and lysozyme do not produce any changes of the glycocalyx, while hyaluronidase and neuraminidase lead to partial and subcomplete removal respectively. Cells stripped of their glycocalyx coat by neuraminidase do not detach from the support and do not show any signs of toxicity. There is complete reconstitution of the glycocalyx within 24 hr.


Ultrastructural studies of keratinized epithelia of the mouse. IV. Quantitative studies of lysosomes. Electron microscope cytochemical and simple morphometric studies have permitted an estimate to be made of the absolute numbers of lysosomes present in various cell layers of murine epidermis. Most lysosomes appear to be present in basal layer keratinocytes with few being detected in Langerhans cells or in granular layer keratinocytes. The observation that lysosomes are not numerous in any of the strata is discussed with respect to an alternative explanation for the presence of diffuse acid hydrolase activity in the granular layers.


Ultrastructural localization of in vivo bound immunoglobulins in bullous pemphigoid--a preliminary report. The ultrastructural location of in vivo bound immunoglobulins in a case of bullous pemphigoid was determined by coupling peroxidase to antihuman gamma globulin. Immunoglobulin deposits were found exclusively in the space between the basal cells and the basal lamina. The location of the immunoglobulin in bullous pemphigoid thus differs from that in lupus erythematosus where immunoglobulins are found mainly below the basal lamina.


Morphological and functional identifications of catfish retinal neurons. I. Classical morphology. The morphology of the catfish horizontal cells is comparable to that in other fish retinas. The external horizontal cells contact cone receptors and are stellate in shape; the intermediate horizontal cells are even more so and contact rod receptors. The internal horizontal cells constitute the most proximal layer of the inner nuclear layer and may possibly be, in reality, extended processes from the other two horizontal cell types. Bipolar cells resemble those in other teleost retinas: the size and shape of their dendritic tree encompass a continuous spectrum ranging from what is known as the small to the large bipolar cells. The accepted definition of amacrine cells is sufficiently vague to justify our originating a more descriptive and less inferential name for the (axonless) neurons in the inner nuclear layer which radiate processes throughout the inner synaptic layer. These starbust and spaghetti cells vary considerably in the character and extent of their dendritic spread, but correlates exist in other vertebrate retinas. Ganglion cells are found not only in the classical ganglion layer but displaced into the inner nuclear layer as well. Several types can be distinguished on the basis of cell geometry and by the properties of their dendritic tree. Not all of the categorization corresponds with previous descriptions; our findings suggest that some reorganization may be necessary in the accepted classification of cells in the proximal areas of the vertebrate retina. A subtle yet remarkable pattern underlies the entire structure of the catfish retina; there exists a definite gradient of size within a particular class of cells, and of configuration among the subclasses of a specific cell type. It remains to be seen if these morphological spectra bear any functional consequences. The fact that the structure of the catfish retina most closely resembles those of other phylogenetically ancient animals, such as the skate and the dogfish shark, testifies to its primitive organization; morphological and functional mechanisms discernible in this simple system may, therefore, be applicable to the retinas of higher ordered vertebrates.


Morphological and functional identifications of catfish retinal neurons. II. Morphological identification. In this study the morphological origins of the responses from the catfish retinal neurons evoked by step inputs were determined by injecting intracellularly a dye, Procion yellow. A method was devised to view the dye-injected neurons in flat mount to study their dendritic expansion; later the same neurons could be sectioned radially to locate the levels of their somata or dendritic expansion. The results of this study show the inherent danger of identifying dye-injected neurons only in a radial or tangential view. Bipolar cells could be identified functionally without any ambiguity by changing widely the stimulus parameters, because the stimulation of their receptive-field center and surround gave rise to responses of opposing polarity. We found no exception to this rule. The neurons in the proximal layers produced a large variety of responses which could not be segregated into two such classes as the amacrine and ganglion cells. In this part II they were classified into three broad categories: neurons giving rise to sustained, transient, and spiking responses. The demarcation among the three types, morphologywise and functionwise, was vague and not well established. The sustained responses were recoreded from the starburst and spaghetti neurons (part I (9)) which correspond to Ramón y Cajal's (2) amacrine cells. The transient responses, whose patterns were largely invariant of the changes in the stimulus parameters, were recorded from a class of neurons with spindle-shaped somata in the INL. We do not know whether they had axons or not, but we will not be surprised if a future study defines them as a class of ganglion cells. Responses with or without spike discharges were recorded from a class of neurons which were identified as ganglion cells. Observations made on a large number of Procion-injected neurons in both flat-mount preparations and radial sections show that finer dendritic arborizations were not seen in the dye-injected neurons although the presence of such branches was proved in the Golgi preparations. Probably this was due to the weak contrast of the Procion-injected cell against the tissue background, rather than the failure of the dye to diffuse into finer branches. We recognize the severe difficulty involved in the traditional approach of identifying a class of neurons based on typical but subjectively selected functional and structural samples. Neurons have to be classified statistically according to their (quantitative) parameters. (cont'd)


Migration and embolization of macrophages to the lung--a possible mechanism for colloid uptake in the lung during liver scanning. Estrogenic stimulation of the RES in animals will result in the mobilization of large numbers of phagocytic cells from their natural sites of storage, chiefly the liver, spleen, and bone marrow, into the intravascular space. These cells are trapped in the pulmonary capillary bed and retain their ability to phagocytize colloidal particles. This is suggested to be the mechanism whereby increased lung uptake of colloidal radiopharmaceuticals is observed in some patients with liver diseases or other conditions stimulating the RES. It is further postulated that the known increase of estrogenic hormones in some patients with liver disease may be the in vivo stimulation resulting in increased mobilization of RES cells to the lung and subsequent isotope entrapment. It is possible that prognostic information can be obtained from this finding; however, its exact significance cannot be determined from this present study.


Relative tissue distribution of radioactivity in rats with endocrine "autonomous" breast carcinomas after 3H-,99mTc-, and 64Cu-bleomycin. The localization of 64Cu-, 3H-, and 99mTc-labeled bleomycin was studied in tissues of Fisher rats bearing an endocrine autonomous breast tumor. The 64Cu-bleomycin showed a greater uptake than 3H- and 99mTc-bleomycin in the breast tumor at all time intervals studied, from 2 to 72 hr after the tracer. This same differential uptake was shared by the liver and kidney.


Intraepithelial lymphocytes in the male reproductive tract of rats and rhesus monkeys. Although lymphocytes are never present in 'normal ' seminiferous epithelium, they are found in the terminal portions of the seminiferous tubles near their junctions with the tubuli recti. Intraepithelia lymphocytes are also found in the tubuli recti testis, ductuli efferentes, epididymis and ductus deferens. The ultrastructural morphology of these cells closely resembles that of the intraepithelial lymphocytes in the intestinal mucosa and those obtained from the lymph nodes, spleen blood and thoracic duct. The mucleus  is spherical and is characterized by clumps of chromatin near the nuclear membrane. A thin rim of cytoplasm is usually found, and is remarkably free of most cell organelles except for free ribosomes. Frequently, a blunt cytoplasmic process can be seen extending from one end of the cell. Membrane-bounded granules and other dense bodies are occasionally encountered in the cytoplasm. The possible functional significance of intraepithelial lymphocytes in the male reproductive tract is discussed.


Far-field recorded frequency-following responses: correlates of low pitch auditory perception in humans. The recent demonstration that auditory frequency-following responses (FFR) can be recorded by signal averaging from the human scalp, opened the way for studies correlating FFR with auditory experience. This report describes FFR amplitude changes as a function of stimulus intensity and the addition of masking noise. The first experiment revealed a high degree of consistency both within and across subjects in the latency, phase and waveform of averaged FFR. This experiment also demonstrated a monotonic relationship between average FFR amplitude and stimulus intensity between 40 and 65 dB SL. Results of the second experiment showed a close correlation between the detectability of a tone in a noise masker and FFR amplitude. FFR amplitude diminishes precipitously as noise intensity approaches or exceeds the threshold for masking of the tone. These results are interpreted as emphasizing the role of neural periodicity mechanisms in the preception of low frequencies.


Cortico-striatal evoked potentials in the monkey (Macaca mulatta). A systematic study has been made of topographic organization in the striatum of evoked potentials elicited by stimulation of the cerebral cortex in unanesthetized, comatose monkeys (Macaca mulatta). Stimulation of the dorsal field of the prefrontal convexity elicited potentials primarily in rostral portions of the caudate, while stimulation of the ventral field of the prefrontal convexity elicited potentials in ventromedial areas of the putamen. Stimulation of different points on the precentral and postcentral gyri revealed a distinct somatopic organization of evoked responses in the putamen, although responsive zones in the putamen to precentral and postcentral stimulation showed almost total overlap. An overlap of responsive zones to stimulation of the dorsal prefrontal convexity and the premotor area (area 6) was found in the dorsolateral part of the rostral caudate, while a zone of overlap of responses to stimulation of the ventral prefrontal convexity and "hand" motor area of the precentral gyrus was found in the ventromedial area of the putamen near the commissural level.


Evoked potential correlates of selective attention with multi-channel auditory inputs. Ten subjects were presented with a random sequence of 50 msec tone pips at a rapid rate (averaging one tone every 225 msec). The tones came from four different sound sources or sensory "channels" each having a different pitch (2000,4000,1000, and 500 c/sec respectively) and perceived spatial position (spaced equidistant across the head). Within each sensory "channel" a random 10% of the tones were of a slightly higher pitch (designated as "targets"). The subject attended to one channel at a time for 7.5 min and counted the targets in that channel. The auditory evoked vertex potential elicited by a channel of stimuli when attended was compared with the mean vertex potential elicited by those same stimuli when the other three channels were being attended. The N1 component (latency 80130 msec) measured re a baseline revealed an increase with attention (82% in the baselineN1 measure, P less than 10-). It was concluded that: (1) this N1 enhancement could not be attributed to peripheral mechanisms acting on sensory transmission; (2) this N1 enhancement reflects a "finely tuned" selective attention to one channel of stimuli among several concurrent and competing channels; and (3) a probable relationship exists between the information load on the subject and the magnitude of this EP enhancement with selective attention.


Rhythmic slow wave activity recorded in the ventral mesencephalic tegmentum in the rat. 1. Slow rhythmic theata-type waves were recorded in the sub-interpeduncular ventral mesencephalic tegmentum (VMT) in the rat. This region is one of the parts of the "limbic midbrain area". These waves are recorded during certain attentive waking states, during the execution of voluntary movements and during paradoxical sleep. 2. These rhythmic VMT waves seem to be of the same nature as the theta rhythm recorded in the limbic structures. A lesion of the septum suppresses the slow rhythmic waves at the mesencephalic level as well as at the telencephalic level. 3. Although we have now shown that the mesencephalic and telencephalic slow rhythmic waves have the same pacemaker, the pathways which transmit the theta rhythm to the VMT are not well known. However, it is reasonable to suppose that the fibres of the post-commissural fornix are involved in this transmission.


Hyperactive behavior and EEG arousal reactions in children. EEG arousal reactions and parameters of spontaneous EEG activity were studied in two extreme groups of behavior problem children (11 hyperactives and 11 non-hyperactives), selected on the basis of a rating of motor restlessness the core symptom of the "hyperactivity syndrome". The EEG was recorded in three reaction time experiments: a tone light conditioning paradigm and two series with random stimulation. An automatic analysis of EEG parameters was employed to describe the time functions of alpha amplitudes in the single trial. The main findings are: 1. In periods free from stimulation, hyperactive children have higher alpha and beta amplitudes, more alpha waves and a smaller amount of beta waves. This indicates a lower state of EEG arousal in the hyperactives. 2. The amplitude reduction to tone (in the single trial) develops more slowly in the hyperactive group. This group difference increases over the experimental situations. 3. The arousal responses to tone, in terms of the level of maximum amplitude reduction, become comparably weaker in the hyperactives across the experiments. 4. Under all experimental conditions the hyperactives exhibit shorter arousal responses to the light stimulus than the non-hyperactive children. 5. Reaction time performance of the groups is clearly different, hyperactives showing the longer latencies. 6. Although conditional changes in the arousal reactions to both stimuli are reliably demonstrable in all children, the groups show no difference in the corresponding measures. These findings are discussed under the aspects of activation and of attention behavior of the subjects.


[An electrophysiological study of direct occipito-frontal connections in centrum semi-ovale of Papio papio]. 1. Evoked responses to single visual stimuli (VEP) and driving by intermittent light stimulation (ILS) were recorded with macroelectrodes from the central white matter (centrum semiovale) of 12 Papio papio baboons. 2. Two types of VEP were identified: VEPs with constant morphology, localized in the long associative bundles connecting the occipital, temporal and frontal lobes; VEPs with variable morphology and without any preferential localization; these probably originate from other types of fibres also belonging to the centrum semi-ovale. 3. Concerning the long associative bundles which have been individualized, they might be the equivalent of the occipito-frontal and the superior and inferior longitudinal bundles well known in man. The fusion frequency observed in these bundles during ILS increases from the frontal to the occipital lobe, because of their involvement (particularly in the parieto-temporal region) with other fibres of the centrum semi-ovale also likely to be driven by ILS. The existence of driving by ILS in these bundles demonstrates an activation of the frontal lobe by visual impulses.


The contingent negative variation during a memory retrieval task. Evoked potentials were recorded from the human scalp during performance of a memory retrieval task modeled after a paradigm originated by Sternberg (1966). Subjects were required to decide whether a probe digit was contained in a series of one to four target digits presented a few seconds before. The amplitude of the contingent negative variation (CNV) preceding the probe digit and the speed of CNV resolution after the probe varied as a function of target set size. CNV amplitude was greatest when the set size was one. The smaller the set size, the more positive the evoked potential 300 msec after the probe, regardless of whether a motor response was required.


Evolution of sleep spindles in childhood. Twenty-six normal children (age range range 4-68 months) were studied during Stage 2 sleep which occurred within 20 min preceding or following the first three REM periods of the night. Sleep spindles were measured in Fp1T3. The number, length, and percent of sleep spindle activity were found to be maximal at 46 months of age. Beyond 6 months spindle activity decreased to reach minimal values by 27 months, remained fairly constant to 54 months, then rose again to higher values in the oldest subjects. The mean spindle-wave frequency was 1314 c/sec in subjects younger than 40 months, but was 12-13 c/sec in older subjects. Spindle onsets in Fp1T3 and Fp2T4 were more often concurrent in older as compared to younger subjects. Auditory stimulation (binaural clicks, 60 dB above hearing threshold) affected neither the incidence nor the length of spindles during sleep. Because sizable changes in sleep spindle activity are found between 3 months and 5 years of age, and because such changes are relatively consistent between subjects, it is concluded that sleep spindles recorded between frontal and temporal areas may serve as a useful index of neural maturation in the human subject.


A 16-channel cassette tape recorder system for clinical EEGs. A 16-channel EEG tape recorder system having a frequency response of DC-100 Hz for each channel is described. The system utilized standard commercially available highfidelity audio tape decks in conjunction with specially designed circuits for time-division multiplexing a balanced amplitude modulation


Selective averaging of the intracerebral click evoked responses in man: an improved method of measuring latencies and amplitudes. Individual click evoked responses recorded in the right and left frontal lobe in man have been correlated with different templates, that is, particular wave shapes of evoked responses, and from the maxima of the cross correlation functions individual estimates were obtained of amplitude and latency. Averages were then made of evoked responses having particular amplitude and/or latency values. Using such selected trials for averaging, better results were obtained and artificial amplitude damping avoided. It was found for example that the component N90 varied in latency between 75 and 100 msec and was linked with the behaviour of the contralateral recorded potential amplitude of P150. Furthermore it was found that the biphasic potential N230 P430 was very unstable in latency and the amplitude of the averaged potential using all trials was about 30% too small.


Detection of neuroelectric signals from multiple data channels by optimum linear filter methods. A general mathematical formulation for predicting achievable levels of detection of neuroelectric signals in associated background noise is provided for the case where such data are obtainable from multiple recording loci. The formulation depends upon the signal-to-noise ratios and bandwidths of the incorporated data channels and on the degree of noise dependency between channels. The signals are assumed to relate to the same event such as the production of an incipient movement but need not have the same waveshape. The detection technique is based upon passage of the data through a series of optimum linear filters. The outputs of the filters can either be summated in analog fashion prior to making the detection decision, or their separate outputs and separate detection decisions can be treated combinatorially to determine a detection decision for the aggregate. The former method is superior to the latter for small numbers of data channels. The latter method may be preferable where variation in signal latency exists between channels. Incorporation of information from multiple channels with independent noise can result in significant improvement over detection signals from a single channel provided that the signal-to-noise level of each additional channel exceeds that of the aggregate divided by square rootK, K being the total number of added channels. However, the presence of noise dependency between channels may severly restrict the degree of imporvement realizable through the multiple channel detection operation, irrespective of the number of added cha-nels. The implication of this result on the possibility of using EEG signals predicting incipient movement to control the operation of a motor prosthesis is profound. Inter-channel noise dependency with correlation coefficienr filter method of detection levels required for prosthesis operation. Zero lag correlation coefficients between electrical recordings from separate cortical loci both in man a


Direct depth recording of the striate cortex during REM sleep in man: are there PGO potentials? Direct recording from the striate cortex was performed in an adult patient and the activity which occurred during paradoxical sleep is described. Monophasic and diphasic potentials, isolated or grouped in bursts, were observed, with no strict relationships with oculomotor activity. Arguments in favour of and against these potentials being PGO waves are discussed


Disorganized relations of tonic and phasic events of REM sleep in a case of brain-stem tumour. This study concerns a case of infliltrating tumour of the pons in which a night sleep recording was performed. Selective disorganization of REM sleep was observed, with lack of muscular atonia and disturbances of tonic-phasic relationships. These data are discussed with respect to the results of local destructions performed experimentally in animals.


Effect of ochratoxin and aflatoxin on serum proteins, complement activity, and antibody production to Brucella abortus in guinea pigs. The effect of ochratoxin alone and in combination with aflatoxin and Brucella abortus antigen on complement activity, serum proteins, and antibody response in guinea pigs was investigated. Ochratoxin did not affect complement activity or antibody response and there was no interaction between ochratoxin and aflatoxin on any of the responses tested. Ochratoxin significantly lowered the level of beta-globulin in serum of guinea pigs. There was no significant interaction between aflatoxin and antigen on lowering of the serum albumin levels of guinea pigs.


A supravital cytodiagnostic stain for urinary sediments. A mixture of aqueous solutions of National fast blue, a copper-phthalocyanine dye, and pyronin B, a red xanthene dye, when added to fresh urinary sediment, supravitally stains benign or malignant cells and the various types of casts and their inclusions. The stain facilitates identification of the formed elements and particularly aids in the differentiation of polymorphonuclear leukocytes from lymphocytes, histiocytes, plasma cells, and renal tubular cells. A variable staining of casts and their inclusions has been observed. Tumor cells may be recognized by nuclear abnormalities or, in case of hyperchromatic tendency, by a very rapid and early uptake of dye preceding that of the surrounding cells. The staining method is rapid and simple enough for routine urinalysis and screening procedures.


Cyclophosphamide treatment in steroid-sensitive nephrotic syndrome of childhood. An  8-week course of 3 mg. per kg. body-weight per day of cyclophosphamide was administered to eighty-two children with steroid-senstitive nephrotic syndrome. One died, and of the remainder, 69% were in remission after 1 year and 44% after 4-years. Older children and those in whom cyclophosphamide was given during a steroid-maintained remission fared better.


Bacterial colonisation of jejunal mucosa in acute tropical sprue. Fifteen of sixteen Caucasians with acute tropical sprue were founc to have numerous aerobic bacteria closely associated with the mucosal layer of the proximal jejunum. Four species of Enterobacteria were grown in eleven patients, and concentrations were higher in the mucosal patients than in the jejunal fluid. Only one of eight control cases with similar tropical exposure but without mucosal morphological abnormalities had any similar bacteria in the mucosal biopsy. In no case were Bacteroides isolated. Since clinical and biochemical improvement only occurred on treatment with tetracycline when enterobacteria were eliminated from the mucosa, it is suggested that these organisms may be responsible for persisting jejunal abnormalities in tropical sprue.


12-month follow-up of yoga and bio-feedback in the management of hypertension. Twenty hypertensive patients treated by psychophysical relaxation exercises were followed up monthly for 12 months. Age and sex matched hypertensive controls were similarly followed up for 9 months. Statistically significant reductions in blood-pressure (BP) and antihypertensive drug requirements were satisfactorily maintained in the treatment group. Mere repetition of B.P. measurements and increased medical attention did not in themselves reduce B.P. significantly in control patients.


A critical search for evidence of changes in levels of circulating IgE in patients with cancer. Serum-IgE levels in 95 patients with various advanced malignant conditions were determined by the radioimmunosorbent test. The results obtained did not support the claims of other workers that a high proportion of untreated cancer patients have extremely high circulating IgE levels, attributable to the release of a tumour constituent which interferes with this radioimmunoassay procedure.


Hypertensive crisis, erythrocytosis, and uraemia due to renal-artery stenosis of kidney transplants. Two patients with kidney transplants had hypertensive encephalopathy and rapidly progressive kidney failure 10 weeks and 18 months postoperatively. In one patient renal failure was associated with erythrocytosis. Absence of proteinuria, despite progressive renal insufficiency in both patients, suggested that these abnormalities were not due to rejection episodes. Subsequently, angiography proved that each of these patients had renal-artery stenosis. Surgical repair of this lesion increased creatinine clearance at least threefold, and the hypertension and erythrocytosis disappeared. Apparent "rejection" episodes in which there is no proteinuria should alert clinicians to the possiblity of renal-artery stenosis of the graft. Restoration of kidney function and amelioration of hypertension may follow revascularisation, even after many months of renal ischaemia producing  severe uraemia.


Parvovirus-like particles in human sera. A parvovirus-like antigen has been found in sera of nine healthy blood-donors and two patients. Its pathogenicity is unknown, but 30% of adults possess specific antibody. The new agent can be confused with hepatitis-B antigen both morphologically and serologically.


Adenosine-deaminase deficiency in a child diagnosed prenatally. Deficiency of red-blood-cell adenosine deaminase (R.B.C.-A.D.A.) has been reported in a proportion of patients with the autosomal recessive form of severe combined immunodeficiency (S.C.I.D.). In a family in which a child had died with S.C.I.D., R.B.C.-A.D.A. levels in the parents and other members of the family were compatible with a heterozygous state for A.D.A. deficiency. Cultured amniotic-fluid cells obtained from a subsequent pregnancy contained less than 1.5% of A.D.A. activity of normal amniotic cultures. The prenatal diagnosis of A.D.A. deficiency was confirmed at birth by the absence of A.D.A. ACTIVITY IN THE CHILD'S RED-BLOOD-CELLS. Clinical and laboratory findings in this child are similar to those of the sibling who had died with S.C.I.D.


Low-renin hypertension: nephrosclerosis? A substantial group of patients with essential hypertension have abnormally low renin levels which respond poorly to stimulation. Important differences in response to therapy and in prognosis have been described between these and other hypertensive patients. It is suggested that the vascular changes of nephrosclerosis, which may be seen in both hypertensive and normal subjects, result in a reduction of afferent arteriolar distensibility, with impairment of basal renin secretion and responsiveness. This hypothesis accords with both of the known clinical characteristics of low-renin hypertension and with the known effect of arterial changes upon the activity of other baroreceptors.


Role of Fc receptors in herpes simplex virus infection. It is suggested that Fc receptors which appear on the surface of cells infected by herpes-simplex virus confer a biological advantage on the virus--perhaps by binding immunoglobulin molecules or antigen-antibody complexes on the cell surface, thus blocking viral antigenic sites, or by consuming antibody directed at surface viral antigen or by modifying replication of the virus.


Ethics of selective treatment of spina bifida. Report by a working party. Ethical problems in medicine usually arise when normal guiding principles appear to be in conflict. In the case of babies with severe spina bifida, or similar abnormalities, two such fundamental principles may be applied with opposing conclusions. The first is that any decision requires an estimate of the balance of suffering and happiness for those concerned in an action, and the other is the assertion that human life is sacred. Resolution of the conflict between these is possible by looking at the problem in a different and less fundamental way, and one such approach is through the concept of ordinary and extraordinary means. While man does not possess power of absolute ownership over life, his duties of stewardship require him to use ordinary means of safeguarding life; he may use, but is not obliged to use, extraordinary means. The distinction between ordinary and extraordinary means may vary with circumstance, and so the application of this principle involves decisions at a third or more practical level. These include an assessment of the child's abnormality, of the effects of this upon the quality of life possible for the child, and of the burdens that will be placed on the family and society. At each level the ethical decisions involve complex choices, and clearly any present policies must be regarded as temporary unavoidable compromises rather than as final solutions.


Shigellosis in day-care centres.

Shigellosis in day-care centres. Increasing numbers of outbreaks of shigellosis in day-care centres have been reported to the Center for Disease Control since 1972. Investigations reveal certain unique epidemiological features of shigellosis in this setting. Attack-rates tend to be higher than in outbreaks in primary schools, and epidemiologically these outbreaks resemble those in custodial institutions. Person-to-person transmission is the usual mode of spread; secondary spread within households is common, and there may also be significant spread to the community at large. Preventive measures should be directed at children, staff, and the day-care centre environment. Control of outbreaks may require closing the centre and must include separation of infected and uninfected persons, judicious use of antibiotics, and correction of deficiencies in hygiene and health education. Improved surveillance of shigellosis in day-care centres will be an aid in efforts toward controlling this increasingly important public-health problem.


Short-course chemotherapy in pulmonary tuberculosis. A controlled trial by the British Thoracic and Tuberculosis Association. The results of short courses of chemotherapy using rifampicin plus isoniazid, supplemented for the first two months by streptomycin or ethambutol, in patients with newly diagnosed pulmonary tuberculosis, have been studied. 174 patients with little or no cavitation received six months chemotherapy. 1 (0.6%) failed to convert to culture negative during treatment and 5 (3%) relapsed in the twelve months after the end of treatment. In 177 patients with similar disease, twelve months chemotherapy was 100% effective in rendering the sputum culture negative and in preventing relapse in the six months after the end of treatment. 151 patients with more extensive cavitation received chemotherapy for nine months; this was 100% effective in sputum conversion and in preventing relapse in the nine months after the end of treatment. In 155 patients with similar disease, the eighteen-month regimen was uniformly successful in sputum conversion. The rifampicin plus isoniazed regimen was well tolerated, producing adverse effects which warranted withdrawal from the study in only 3.6% of patients. Comparison of ethambutol with streptomycin as a third drug given for the first eight weeks showed no significant difference in the rate of sputum conbersion nor in the incidence of relapse. Streptomycin produced significant adverse effects in 8% of patients whilst ethambutol caused none. Chemotherapy with rifampicin plus isoniazed for nine months, supplemented initially by ethambutol, is more acceptable than standard chemotherapy for eighteen months, is highly effective in sputum conversion, and has resulted in no relapses over a nine-month follow-up period. Further follow-up is being continued to confirm that relapse does not occur.


Leukaemia and lymphoma patients interlinked by prior social contact. Patients with either leukemia or lymphoma were asked if they had close personal associations with other patients before the onset of disease. Iinitial interviews indicated that several patients  could be interlinked into social clusters. Tumour-registry records were used to contact each patient (or a surviving relative) diagnosed during the years 1964-73 in three areas of West Virginia. Close personal associations, antedating the onset of disease in 1 or both individuals of each linkage pair, were detected in 14 of 23 (61%), 14 of 22 (68%), and 6 of 8 (75%) patients from these three areas during this ten-year period. In addition, among 28 randomly selected patients with Hodgkin's disease from various parts of the United States, 10 (36%) had direct or indirect close personal associations with 17 other patients with leukemia or lymphoma. Patients with leukemia or lymphoma frequently are interlinked by prior close personal associations to other patients with these diseases.


Treatment of small-cell carcinoma of bronchus. A randomised trial comparing radiotherapy with a multiple chemotherapy regimen in 68 patients with small cell carcinoma of bronchus is reported. Although overall survival was  poor, radiotherapy resulted in significantly longer survival, better amelioration of symptoms, and less  side-effects than chemotherapy. Patients achieving  complete or partial remission on radiotherapy relapsed mainly with extrathoracic disease, in contradistinction  to those treated with chemotherapy whose thoracic disease recurred.


Lord treatment of haemorrhoids. Four-year follow-up of fifty patients. A prospective study as been carried out on fifty patients with haemorrhoids treated by the Lord method who were followed up for at least four years. All patients were interviewed and examined regularly during the observation period. 75% of patients were rendered symptom-free or considerably improved. Apparently the long-term results of this method of treatment can be predicted from the results at eighteen months after operation.


Urinary-tract infection: localisation and virulence of Escherichia coli. Virulence of 15 strains of Escherichia coli from the human upper urinary tract was compared with that of 16 strains from the lower urinary tract, using an ascending infection in the mouse. No significant difference was found. There was no significant difference in frequency of K antigen and ability to ferment dulcitol between 32 lower strains and 31 upper strains. However, 22 strains containing K antigen, regardless of anatomical site of localisation, were more significantly likely to cause infection than 9 strains with no antigen. Similarly, 23 dulcitolfermenting strains, regardless of site of localisation, were significantly more likely to cause infection than 8 non-fermenting strains.


The small-intestinal mucosa in cow's milk allergy. Two infants investigated for allergy to cow's milk proteins exhibited a local reaginic reaction in the small intestine after ingesting cow's milk, as shown by increased mucosal IgE plasma-cells and degranulation of mast cells. IgM plasma-cells and the staining of connective tissue and basement membranes with antisera to IgG and C3 complement were also increased, indicating several simultaneous immune reactions in the intestinal mucosa. These findings may provide a sound basis for diagnosis of such an allergy and for the treatment of similar patients with disodium cromoglycate.


Medical manipulation of the ductus arteriosus. Prostaglandin E-1 was infused into two children with cyanotic congenital heart-disease where patency of the ductus arteriosus was necessary to maintain arterial oxygen  saturation. With each infusion oxygen saturation rose, probably as a result of dilatation of the ductus. Administration of the non-specific antagonist of prostaglandin synthesis, indomethacin, to one patient was associated with a fall in arterial saturation. The prevention of ductus closure by p.g.E-1 infusions over the first few weeks of life is a possiblility.


Probable identification of an HL-A second-locus antigen associated with a high risk of nasopharyngeal carcinoma. An HL-A antigen profile comprising an increased frequency of HL-A2 and undetectable second-locus antigen(s) in Chinese patients with nasopharyngeal carcinoma (N.P.C.) has been reported. To investigate whether the deficit of second-locus antigen(s) had a genetic basis, sera from parous women in Singapore were screened for anti HL-A activity corresponding to the second-locus "bland". A second-locus (Singapore-2) was identified which seems to be associated with a high risk of N.P.C.


Model for extrusion of insulin beta granules. Considerable controversy surrounds the mechanisms of insulin secretion. This  hypothesis attempts to explain the events which may lead to insulin extrusion through the beta-cell membrane. The role of various effectors of insulin secretion on the activities of  membrane-bound enzymes is discussed. Glucose, without effect on these enzymes, did induce insulin secretion from insulin granules and plasma membranes in vitro. The model  proposes a mechanism whereby glucose may trigger first-phase insulin secretion; reinforcing mechanisms, such as raised levels of cyclic adenosine monophosphate, could augment subsequent secretion.


Mode of insulin action.

Mode of insulin action. A unifying hypothesis is proposed for the mechanism of insulin action in adipose tissue. Insulin both induces displacement of Ca++ from a membrane-bound pool and inhibits efflux of the ion, thereby facilitating a rise in intracellular free Ca++ concentration. The former effect could enhance the transport of substrates and ions into the cell, while the latter modulates the activity of some intracellular enzymes to stimulate glycogenesis, lipogenesis, and decrease lipolysis and glycogenolysis. The calcium ion might act as the missing second messenger for insulin action.


A new program for investigating adult human skeletal muscle grown aneurally in tissue culture. With our new "explant-reexplanting" technique, abundant growth of mature human muscle in long-term tissue culture was achieved,and with the "sandwich" technique several histochemical reactions were obtained on serial cross sections of the cultured fibers. An advanced degree of maturation but lack of differentiation into reciprocally staining fiber-types was demonstrated. For electron-microscopic and electronmicroscopic-histochemical study, a method was developed in which the embedded fibers of greatest potential interest were identified by light microscopy and punched out by our specially-designed hollow drill. This selection procedure is critically important when the goal is to study in cultured diseased human muscle: (1) successive stages of development and (2) certain structural changes that often occur only in some fibers and only in certain regions of those fibers. The electronmicroscopic-histochemical appearance of developing cultured muscle fibers correlated well with the fresh-frozen light microscopic histochemical cross-sections and longitudinal whole preparations of similar fibers.


Increased incidence of adenocarcinoma of uterine cervix. A greater than expected incidence of adenocaricinoma of the uterine cervix is reported. Among 41 cases of cervical carcinoma, 14 (34%) were adenocarcinoma. Clinicopathologic data for these cases are summarized. Eleven of the 14 cases were pure adenocarcinomas; 3 were mixed adenosquamous carcinoma. The value of cytopathology is demonstrated in the 7 of 9 pretreatment cervical cytologies whereby adenocarcinoma was indicated (an accuracy rate of 78%). The other 2 revealed abnormal cells in which malignancy was a possibility. Three cases clinically were initially considered endometrial adenocarcinoma, but by our classification criteria, including Alcian blue staining for cervical mucin content of acid mucopolysaccharide, they were more specifically identified as primary endocervical in origin.


Type C RNA tumor virus isolated from cultured human acute myelogenous leukemia cells. Previously, type C RNA tumor virus-related components have been described in blood leukocytes from patients with acute myelogenous leukemia. These components, for example, reverse transcriptase, have been shown to be most closely related to those from two oncogenic subhuman primate type C viruses (woolly monkey sarcoma virus and gibbon ape leukemia virus). Now, we report the continuous production of budding type C viruses with the same characteristic reverse transcriptase by three separate culturings of leukocytes from a single bleeding from a patient with acute myelogenous leukemia. These isolations were made possible by the discovery of a source of conditioned media which sustains exponential growth of human myelogenous leukemia cells in liquid suspension culture.


Cytological, cytochemical and immuno-fluorescence studies with Dugbe virus - a new Nigerian tick-borne virus. Dugbe virus, a new tick-borne arbovirus from Nigeria, was propagated in continuous porcine kidney (PS) cells, and the cytopathology studied by various staining techniques such as May-Grunwald-Giemsa, methyl-green pyronine, Feulgen, and immuno-fluorescence. The gross cytopathology was slight and infected cells continued to undergo normal mitotic divisions. The outstanding cytopathologic feature was the presence of large basophilic intracytoplasmic inclusion bodies, which were pyroninophilic and Feulgen negative. By immunofluorescence these inclusions were shown to be depots of viral antigen; specific fluorescence was confined to the cytoplasm throughout the replication of the virus.


Morphologic observations of mycoplasmas and Neisseria gonorrhoeae in associated growth patterns. Mycoplasma hominis and T-colony mycoplasmas were observed growing among or developing within gonococcal colonies on primary isolation plates streaked for detection of N. gonorrhoeae in urogenital specimens. The frequency of such association of mycoplasmas with gonococci was as high as 84% among patients screened for gonorrhea in several Social Hygiene Clinics of the City of New York, Department of Health, Bureau of Venereal Disease Control. The individual morphology of both mycoplasmal and gonococcal colonies was characteristic when viewed through the light microscope, and their associated growth was maintained throughout numerous serial transfers on agar culture media. Electron microscopy of such interrelated colonies revealed nipple-like projections on the gonococcal cell walls, to which the mycoplasmas appeared to be firmly attached. These morphologic observations are presented and discussed.


Comparative evaluation of the Limulus assay and the direct Gram stain for detection of significant bacteriuria. A double-blind study comparing the Limulus in-vitro endotoxin assay with the direct Gram stain of uncentrifuged urine for detection of significant bacteriuria was performed. One-thousand seventy-seven urine specimens were examined by the two methods and the results compared with results of quantitative urine cultures. Two hundred three samples produced growth of greater than 10-5 organisms per ml. urine. The Limulus assay detected 86.2% of these specimens, and 98.8% of urines that contained greater than 10-5 Gram-negative bacilli per ml. The Gram stain procedure detected only 69.5% of urines containing greater than 10-5 organisms per ml. and 74.5% of specimens with greater than 10-5 Gram-negative bacteria per ml. urine. The Limulus assay demonstrated both greater sensitivity and greater specificity than the Gram stain procedure. Moreover, the Limulus test is much less susceptible to errors of interpretation than methods involving microscopy.


Core isoelectrofocusing.

Core isoelectrofocusing. An improved method of isoelectrofocusing is described. A plastic rod is centered in a tube and the lumen is filled with gel. After separation the rod is withdrawn and replaced by staining solution. Staining and destaining are quick and simple. The gel remains stabilized in the tube allowing no distortion or breakage and permitting accurate localization of separated bands.


A microprecipitation test for rapid detection and identification of Venezuelan, eastern and western equine encephalomyelitis viruses. The development of a new diagnostic procedure for the identification of Venezvelan, eastern and western equine encephalomyelitis (VEE, EEE, WEE) viruses is described. The procedure utilizes virus precipitation with reference fluorescein-conjugated gamma globulin, followed by cellulose acetate electrophoresis. Clinical specimens containing varying concentrations of virus yielded, in primary duck embryo cell culture, sufficient virus for detection within 22 to 44 hours. Identification of VEE, EEE and WEE virus in specimens was accomplished by microprecipitation within this time. In contrast to conventional identification methods, our procedure eliminates the cost of utilizing laboratory animals and considerably reduces the time required for virus identification.


Serologic classification of scrub typhus isolates from Pakistan. Detailed serologic characterization of 79 isolates of Rickettsia tsutsugamushi from Pakistan was performed by using complement fixation and direct immunofluorescence techniques for comparison with three prototype strains. Seventy-one were of the Karp serotype and one was of a Gilliam serotype. Seven isolates were multiply-reactive: one with Karp and Gilliam, 3 with Karp and Kato, and 3 with Karp, Gilliam and Kato, No strain failed to react with at least 1 of the 3 prototype antisera. No correlation of antigenic types with local geographic factors, animal hosts, vecotr mites, or specific strain virulence was observed. These findings suggest the possibility that antigenic heterogeneity may be more restricted in areas peripheral to the geographic epicenter of scrub typhus endemicity, that the serotypes are relatively stable genetically and that new geographic variants are probably infrequent. The importance of these findings to the practical problems of immunoprophylaxis and serodiagnosis are discussed.


Glomerular involvement in human kala-azar. A light, immunofluorescent, and electron microscopic study based on kidney biopsies. Glomerular involvement characterized by mesangial cell proliferation with fibrillar thickening of the axial region and deposits of immune complexes is reported in three human cases of kala-azar. IgG was seen in all 3 and Igm in 2 patients. Complement (C3) was detected in the glomeruli in all cases and fibrinogen in the only case in which it was tested for. The deposits appeared mainly along the mesangium and their staining was particularly strong for complement and IgG. Electron microscopy detected granular electron dense deposits mainly close to mesangial cells. In one case clumps made us of electron dense lamellae were seen in the glomerular basal membrane interpreted as evidence of focal membranolysis. No granulocytes were seen in the glomeruli. Attempts to demonstrate antigen were unsuccessful. The pattern of the lesion resembles that described in the kidney of human cases of hepatosplenic schistosomiasis, and the distribution of the deposits suggests that relatively large, poorly soluble complexes formed either in the presence of excess antigen or, under certain circumstances, in the presence of excess antibody, are trapped in the glomerular capillaries. The aggregates are partially shunted to the mesangial cells, which enlarge and proliferate.


Histamine release during antigen inhalation in experimental asthma in dogs. Histamine release after antigen inhalation was studied in 12 dogs sensitive to nematode antigens. In 19 experiments, histamine was detected in arterial plasma after antigen inhalation; its concentration was correlated with changes in airflow resistance of the respiratory system (Rrs) (per cent change above control equals 132.3 plus 250 log histamine concentration). Histamine was released from the lung and was not attributable to the concomitant hypoxia. In 6 dogs given aerosols of dilute antigen and in 4 dogs given aerosols of compound 48/80, Rrs increased significantly, but no histamine was detected. Histamine may have been released close to airway receptors, inducing bronchoconstriction, but in amounts undetectable in arterial plasma. In 6 dogs, administration of 48/80 caused partial depletion of histamine stores but prevented the response to antigen inhalation in only one of 6 dogs tested. The close correlation between arterial histamine concentration and Rrs, the qualitatively similar response to antigen and 48/80 aerosols, and the inhibition of the response to antigen when histamine was depleted completely from the lung tissues suggests that chemical mediators are critically important in antigen-induced airway reactions.


Implications of immunologic methods for measuring antihemophilic factor (factor VIII). Recent immunologic studies have provided important new information about the nature of AHF deficiency diseases and the structure and synthesis of this protein. They provide, moreover, a considerably improved ability to identify the carrier state in hemophilia A. Additional progress may be possible in the identification of carriers and of hemophilic patients at risk of antibody formation, but it will require a different  approach to these problems. While preliminary goals have been obtained by using antibodies that identify antigenic determinants shared by normal and nonfunctional AHF, further progress will require the capacity to identify differences between the normal protein and the nonfunctional AHF-like molecules in hemophilic plasma.


Ancillary measures in treatment of myeloma. Use of immune serum globulin, fluoride, or androgen. We reviewed the efficacy of three agents advocated as ancillary therapy in myeloma patients. Intramuscularly administered immune serum globulin (gamma globulin) was ineffective in preventing infection. Hemoglobin level was improved in some myeloma patients receiving androgens. However, the response rate and the degree of leukopenia or thrombocytopenia were not superior with androgen-melphalan-prenisone combination therapy, as compared with those resulting from the two-drug combination without androgen. A controlled study evaluating androgen plus melphalan has not been done. The long-term administration of fluoride, supplemented by calcium and androgen, induced radiologically apparent bone fluorosis, but strengthening of lytic bone was not observed. Neither objective nor subjective benefit was demonstrated in a controlled study comparing the effects of fluoride (without calcium supplement) with those of the placebo.


Biological properties of myeloma proteins. The paraproteins frequently cause major symptoms in patients with plasma cell dyscrasias. This may be due to their quantity in the circulation, to some unusual physicochemical property, or to a biological effect resulting in interaction with other serum proteins. Detection of antibody-combining activity in myeloma proteins has led to important new information on combining-site structure and the kinetics of antigen-antibody-combining activity. Some antibody-combining specificities seem to be present in a higher than expected frequency. As yet, no major therapeutic advances have followed this more precise characterization of the paraprotein, though some interesting possibilities have been explored in animal models.


The human choroid plexus and autoimmune nephritis. The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.


Mucosal histochemistry in secretory otitis. Mucosal biopsies were taken from 20 ears with secretory otitis media (glue ear) and histochemical stainings were made for comparison with data obtained from biochemical analysis of the fluids. Acid phosphatase, lactate dehydrogenase (LD), and malate dehydrogenase (MD), the activity of which in the ear fluids was 20 to 30 times higher than in serum, were found to appear as strong precipitates in the middle ear epithelium, particularly in the top layer. Alkaline phosphatase activity was only exceptionally seen in the epithelium but appeared in the capillaries and histiocytes. Nonspecific esterase appeared irregularly in the epithelium and regularly in histiocytes. The latter two had lower activities in ear fluids than in serum. Epithelial secretory cells and subepithelial glands and cysts showed strong alcian blue (AB)-positive staining. Positive material appeared also in the cytoplasm of the epithelial cells and in the intercellular substance. Distinct PAS-positive staining appeared in the columnar epithelium and particularly in the free mucus on top of the epithelium but was less promounced in the glandular structures and absent from the cysts.


Search for C-type particles in human neoplasia. The salient biologic and morphologic characteristics of RNA tumor (oncornavirus) virus are reviewed. The ultrastructure of replicating oncornaviruses is illustrated in detail. C-type particles wide spread in at least three orders of animals were sighted in human sarcomas and leukemias. One case, an infantile fibrosarcoma, is presented from our cases surveyed for the presence of C-type particles. Tissue cultures derived from this tumor contained viral particles and had an elevated reverse transcriptase activity associated with the presence of 70 S RNA. The particles were larger (125 to 150nm) than those of the murine or avian Type C particles.


The antibody-enzyme analogy. Characterization of antibodies to phosphopyridoxyltyrosine derivatives. Stable analogs of the crucial Schiff base intermediate of enzymatic and nonenzymatic pyridoxal phosphate catalysis have been used as haptens for induction of specific antibodies. N-(5-phosphopyridoxyl)-3'-amino-L-tyrosine and its conformationally distinct cyclized derivative resemble the Schiff base formed upon mixing tyrosine with pyridoxal phosphate. These compounds were covalently coupled to a protein carrier via the 3'-amino group so as to confer a prescribed orientation, with the coenzyme region farthest removed from the carrier. A third antigen, with the phosphopyridoxyl group alone as the hapten, was prepared by linkage of pyridoxal phosphate directly to free amino groups on the carrier protein. Antibodies elicited for each determinant were purified by means of appropriate affinity columns. Antibody heterogeneity was observed in that different species could be separated from a given serum by sequential elution from the affinity columns with 1 M sodium phosphate buffers of pH 7.6, 5.2, 2.6 and 1.5. In assays of quantitative precipitation, inhibition of precipitation, equilibrium dialysis, and fluorescence quenching, antibodies to the phosphopyridoxyltyrosine haptens showed specificity for the phosphorylated form of the coenzyme and binding activity for both the coenzyme and tyrosine portions of the hapten. Antibodies to the phosphopyridoxyl groups alone did not display a similar reactivity toward the tyrosine portion of the complex haptens. The cyclic and noncyclic conformations of the hapten were serologically distinct, as antibody to each reacted preferentially with the homologous form.


Serum-stimulated lipases (lipoprotein lipases). Immunological crossreaction between the bovine and the human enzymes. A rabbit antiserum prepared against the serum-stimulated lipase (lipoprotein lipase) from bovine milk crossreacted with serum-stimulated lipases from human milk and from human postheparin plasma, but not with bile salt-stimulated lipase from human milk or with salt-resistant lipase from human postheparin plasma. Thus, the serum-stimulated lipase in bovine milk has immunological determinants in common with the serum-stimulated lipases in human milk and in human postheparin plasma. The time-courses for the appearance of serum-stimulated lipase and salt-resistant lipase activities in human plasma after heparin injection were different. The two activities were separated by heparin-Sepharose chromatography. After treatment of postheparin plasma with the antiserum only the salt-resistant lipase activity could be eluted from the column. Thus, these two enzyme activities in postheparin plasma reside in two different enzyme molecules.


Acute lymphoblastic leukaemia: a heterogenous disease. By using several techniques to detect surface markers on T and B lymphocytes, 11 cases of acute lymphoblastic leukaemia (A.L.L.) were studied. In four cases an insignificant number of markers were detected on the lymphoblast populations. In one case a significant number of blasts formed both sheep red blood cell rosettes and Fc rosettes, suggesting a T-cell origin for the neoplastic cells, and in another case the presence of Fc and C3 receptors on the lymphoblast population indicated a B-cell origin. In a further five cases 14-43% of the blasts had detectable surface immunoglobulin. It is concluded that A.L.L. is a heterogeneous disorder, some cases failing to express surface markers and others having either a T-or a B-lymphocyte origin or both.


[Letter: Effect of denervation on the anomalous behavior of acridine orange stained actin in solution]. Effect of superviscous state of AO stained actin in concentrated salts (KCI) significantly decreases two weeks after denervation. These changes of anomalous behaviour of stained action are partially reversible at the long time diasrophy. This phenomenon is suggested to be connected with the structural changes of "denervated" actin, which are reflected in the changes of protein electrostatic region.


Studies on brain-thymus cross-reactive antigens. An antigen(s) shared by mouse brain and thymocytes was studied with the use of a rabbit anti-mouse brain antiserum (RAMB). Full complements of brain-thymus antigen were found on the brains of several mouse strains, including athymic mice, regardless of their theta antigen genotype. Brain-thymus antigen(s) was absent in newborn mouse brains and gradually reached adult levels two weeks after birth. Treatment of mouse brain with trypsin neither decreased nor increased the amount of the brain-thymus antigen available for absorption of RAMB. Mouse brain-thymus antigens were present on rat thymocytes, but not rat brain. The concentrations of brain-thymus antigens were 3- to 4-fold higher in gray matter than white matter. Cross-absorption studies with RAMB and anti-theta antiserum suggest that theta antigen and brain-thymus antigen are two distinct substances, both antigenically and in their anatomical localization on brain cells.


Biological importance of retrograde axonal transport of nerve growth factor in adrenergic neurons. Previous studies have shown that nerve growth factor (NGF) produces a selective induction of tyrosine hydroxylase (TH) in peripheral adrenergic neurons and that NGF is transported retrogradely with a high selectivity from the adrenergic nerve terminals to the perikaryon. In order to investigate the biological importance of retrograde NGF transport, the following experiments have been performed; (a) effect of NGF on TH activity in superior cervical ganglia (SCG) after unilateral injection into the anterior eye chamber and the submaxillary gland; and (b) effect of systemic injection of NGF on TH activity in SCG after blockage of retrograde axonal transport by axotomy. After unilateral injection of NGF into the anterior eye chamber and submaxillary gland of both 8-10-day-old rats and adult mice, the increase in TH activity in the SCG was considerably larger on the injected than on the non-injected side although the adrenergic neurons supplying the two organs do not account for more than 25% of the total number of adrenergic neurons in the SCG. A direct diffusion mechanism could be excluded by the fact that unilateral local injection of [125 I] produced no significant side difference in the accumulation of radioactivity in the SCG 2 after injection whereas after 14 h there was a several-fold difference between the injected and non-injected side. Moreover, the nodose ganglia which are located very close to the SCG exhibited no statistically significant difference in the accumulation of radioactivity at any time. Forty-eight hours after subcutaneous injections of 10 mg/kg of NGF the increase in TH activity of the SCG amounted to 154% on the intact side and to 92% on the axotomized side. However, these experiments do not permit decisions about the extent the axotomy, as such, impaired the response to NGF. It is concluded that the biological effect of NGF results to a considerable extent, from the moiety which reaches the cell body by retrograde transport from the nerve terminals.


Electron microscopic observations of horseradish peroxidase transported from the caudoputamen to the substantia nigra in the rat: possible involvement of the agranular reticulum. The intracellular distribution of horeseradish peroxidase (HRP) transported intraaxonally from the caudoputaminal complex to the substantia nigra has been examined with the electron microscope. The reciprocal axonal connections between the caudoputamen and the substantia nigra permitted observation not only of HRP transported retrogradely from axons and axon terminals in the caudoputamen to the cell bodies of origin in the pars compacta of the substantia nigra, but also provided information suggesting that HRP may be transported anterogradely by neurons of the caudoputamen to their terminals, which are especially numerous in the pars reticulata of the substantia nigra. Special attention was focused on observations which might elucidate the manner in which exogenous proteins are compartmentalized and transported intracellularly. It is suggested that the agranular reitculum is involved in the retrograde transport of proteins which are pinocytosed near the axon terminal and ultimately reach lysosomes in the perikaryon. A possible anterograde movement of HRP may also involve the agranular reticulum. The implications such findings have on the use of HRP in neuroanatomical tracing techniques are also discussed.


Corticothalamic neurons and thalamocortical terminal fields: an investigation in rat using horseradish peroxidase and autoradiography. Subsequent to thalamic injections in rats of horseradish peroxidase (HRP) alone or HRP and [3H]leucine in combination, the cells of origin of the corticothalamic projections and the terminal fields of the thalamocortical projections were identified. HRP-labeled corticothalamic neurons were uniformly found in layers V and VI. They were medium to small in size and always pyramidal in shape with the larger neurons being found in layer V. On the other hand, 3 different patterns for the distribution of thalamocortical terminal fields were observed. The autoradiographic material indicated that in prefrontal cortex the bulk of thalamocortical fibers terminate in layer III while in motor cortex they terminate primarily in layer V. A third pattern was shared by temporal, occipital and parietal cortex where the bulk of thalamocortical fibers terminate preferentially in layer IV. The data derived from the rats which had received thalamic injections of HRP and [3H]leucine in combination indicated that the connections between cortex and thalamus are in general reciprocal. These results are discussed with regard to earlier studies using classical or more recently developed neuroanatomical methods.


Antibacterial activity of antisera against homologous and heterologous Escherichia coli of porcine origin. Fourteen enteropathogenic and five nonenterotoxigenic Escherichia coli strains isolated from pigs were used for producing antisera in rabbits and pigs. These antisera were used in an vitro test system for antibacterial activity against homologous and heterologous porcine E. coli strains. Antibacterial titres were determined against the homologous strains and the percent reduction in CFU/ml caused by a 1/200 dilution of the sera against heterologous strains was determined. The results indicated that following immunization the antibacterial activity of serum against homologous and heterologous strains was significantly increased. This activity did not appear to be influenced by O and K antigen relationships among the organisms or by enterotoxigenicity of the vaccine strains. When antiserum produced against a combination of three enteropathogenic E. coli was tested against 20 strains a wider spectrum of heterologous antibacterial activity was obtained than with antiserum produced against any individual strain. The results indicate the existence in E. coli strains of porcine origin of common antigenic determinants not related to the serological formula and that a selected combination of strains can be expected to induce antibacterial acitivity against a wide variety of serological types of porcine enteropathogenic E. coli.


Immunochemical studies on burro antibodies to Histoplasma capsulatum. Burro antiserum to Histoplasma capsulatum was studied from the viewpoint of precipitating antibody distribution among euglobulins, pseudoglobulins, and immunoglobulin classes. By immunodiffusion analysis it was determined that throughout immunization most of the antibody was euglobular, but there was an increase in pseudoglobular antibody as immunization progressed. By immunoelectrophoretic and immunodiffusion analyses of specifically purified antibody, and antibody non-specifically fractionated by column chromatography and ultracentrifugation, it was established that there was no demonstrable IgM antibody, that most of the antibody appeared to be IgG, and that a gamma1 immunoglobulin, probably IgA or T-globulin, may have been responsible for some of the activity. No major changes in the distribution of antibody among immunoglobulin classes seemed to occur during immunization.


Immunophyletic relationships between actinomycetales and eubacteriales determined by examinations of their cytoplasmic antigens. Cytoplasms obtained from a total of 205 different strains of Actinomycetales, Eubacteriales, Lower Fungi, and Protozoa were examined against selected anti-cytoplasm antisera using the immunodiffusion and counterimmunoelectrophoresis procedures. Immunological relationships between the different genera have been revealed and, in respect to Eubacteriales, the possible immunophyletic determinants have been discerned. Cytoplasms of Enterobacter, Clostridium, Staphylococcus, and Diplococcus were found to retain the significant linkage determinants between large groups of Eubacteriales and Actinomycetales. Evolutionary implications of the findings are discussed.


Basic characterization of a lipid-containing bacteriophage specific for plasmids of the P, N, and W compatibility groups. Preliminary studies have shown that bacteriophages PR3 and PR4, originally isolated on Pseudomonas aeruginosa, resemble the lipid-containing phage PM2 in appearance. Their host range extends intergenerically to species carrying drug-resistance plasmids of the P and N compatibility groups. In this paper, the serological identity of the two isolates is established and it is concluded that they are the same virus, but with some differences in growth characteristics. They contain double-stranded DNA and are probably icosahedra (65 nm) with short (47 nm) noncontractile tails. Their sensitivity to chloroform and low buoyant density in CsCl(1.265 g/ml) indicate that they contain lipid which is probably located in the thickened inner layer of the capsid. A study is made of their adsorption efficiencies to sensitive and resistant bacteria, and it is found that, unlike most sex-specific phages, they adsorb directly to the cell surface and not to sex pili. Their host range is shown to include strains harboring a drug-resistance plasmid of the W compatibility group.


Autoradiographic and fluorescent staining studies of bone marrow chromosomes from a patient with acute granulocytic leukemia. Results of cytogenetic studies of a patient with acute granulocytic leukemia are described. The modal number of chromosomes in cells from bone marrow samples was 43; the karyotype was characterized by missing chromosomes in groups B, C, and E. According to successive studies of the same metaphases by fluorescent staining and autoradiographic techniques, the labeling pattern of chromosomes in leukemic cells was generally similar to those observed in normal cultured leukocytes, whereas the fluorescent pattern of leukemic chromosomes was rather indistinct, and the bright fluorescent pattern of the Y chromosome was not apparent.


Endocrine tumor of the pancreas composed of argyrophil and B cells. A correlated light, immunofluorescent, and ultrastructural study. A correlated morphological study, employing endocrine cell stains, immunofluorescence, and electron microscopy, was performed on biopsy specimens taken from a pancreatic tumor and liver metastases in a woman with hypoglycemic symptoms and high fasting insulin levels. The study revealed the tumor to be composed of two different endocrine cell populations, irrespective of the primary or metastatic growth. The first cell type fulfilled all the morphological characteristics of the islet B cells. The second was argyrophil (with the Grimelius silver method) and showed the morphological pattern of polypeptide-hormone-producing cells. With the lack of a detectable symptomatology, normal blood levels of the hormones other than insulin, and the negative results of a large number of immunofluorescence tests, we were unable to indetify the specific nature of the second type of cells.


Urinary polyamine levels in human cancer. Polyamine levels (putrescine, spermidine, spermine) were determined in 24-hour urine samples by a high voltage electrophoresis technique. Normal values were established in 42 normal volunteers. Thirty-eight of 56 patients with metastatic cancer had two or more levels elevated. Approximately two-thirds of patients with metastatic adenocarcinoma, metastatic squamous cell cancer or metastatic disease to the liver, lings, or bones had elevated levels. All 6 patients with localized malignant tumors had elevated urinary polyamine levels. Elevations were also seen in patients with benign prostatic hypertrophy and bronchial adenoma.


The changing management of childhood Hodgkin's disease. Between 1929 and September 1974, 211 children under 15 years of age with biopsy-proven Hodgkin's disease were treated at Memorial Sloan-Kettering Cancer Center. For analysis these patients were placed into three historical groups which displayed the most marked changes in diagnostic workup and therapy. They are as follows: Pre-1959-80 patients with "clinical" staging, local field radiation therapy, palliative chemotherapy; 1960-1969-86 patients with lymphangiographic staging, extended field radiation therapy, palliative chemotherapy; 1970-September 1974-45 patients with "contemporary" staging, including laparotomy, involved field radiation therapy, and/or multiple drug chemotherapy. Twenty-seven children with Stage IV disease at diagnosis or those with recurrent disease received this multiple drug regimen. This consisted of Adriamycin, followed by combined prednisone, procarbazine, and vincristine, then cyclophosphamide. Drug cycles were repeated every 3-4 months for a period of about 24 months. Twenty-five achieved remission, 20 complete and 5 partial. The median duration of complete remission was 18 plus months. This multidisciplinary management of Hodgkin's disease has shown early, encouraging results. Longer followup is needed to determine that this improvement in survival will persist into adulthood.


Pulmonary mycotoxicosis.

Pulmonary mycotoxicosis. Mycotoxicosis is a term used to define a toxic reaction due to the ingestion of toxins produced by fungi. Oral ingestion, however, may not be the sole means of exposure. We have recently observed ten patients who had inhaled massive amounts of fungi, which resulted in an apparent toxic pulmonary reaction. Immunologic studies showed no sensitivity to various fungal antigen preparations and histologic study of the lung showed a multi-focal acute process, with primary involvement of the terminal bronchioles containing large numbers of various spores. Cultures from lung biopsy material revealed at least five fungal organisms. A one to ten year followup indicates that avoidance of massive reexposure to fungal dust is the key to the prevention of recurrent pulmonary mycotoxicosis.


Concealed extrasystolic ventricular bigeminy with interpolation. The first reported case of concealed extrasystolic ventricular bigeminy with interpolation is described. This arrhythmia is characterized by the presence of both interpolated ventricular extrasystolic beats and a presumed persistent and continuous bigeminal ectopic rhythm with exit block. The distributional pattern of sinus conducted beats in the present case conforms to a formula defining this unusual disorder of rhythm, while the appearance of manifest ectopic beats follows the rule of bigeminy.


[Antibody deficiency states in children]. In more than 2500 immunoelectrophoreses and quantitative immunoglobulin determinations 19 cases of transitory hypogammaglobulinaemia, two cases of sex-linked congenital agammaglobulinaemia, six cases of selective IgA deficiency and nine cases of dysgammaglobulinaemia were diagnosed. In congenital agammaglobulinaemia life-long substitution with gammaglobulin must be instituted. Transitory hypogammaglobulinaemia which occurs mostly at the beginning of the second trimenon usually regresses spontaneously at the age of 15 to 18 months. The increased susceptibility to infections can be overcome by gammaglobulin administration. Dysgammaglobulinaemias with serum concentrations below 400 mg/dl also require gammaglobulin supplements. In IgA deficiency the greatest possible care as regards substitution is indicated because of the danger of severe anaphylactic reactions.


[Immunosuppressive treatment of polymyositis]. Azathioprine (150 mg daily) was given to 14 patients with polymyositis. Most of the patients also received prednisolone (initial dose 80-40 mg daily, maintenance dose 15-5 mg daily). Some patients additionally received 6-mercaptopurine, methotrexate and (or) cactinomycin. Symptoms practically disappeared in three patients, while in four there was marked improvement, in four others moderate improvement occurred. Four patients who were improved had previously received long-term treatment with high doses of corticoids but without response. There were three deaths; treatment had definitely failed in one, in the other two the duration of treatment had been too short. Results were best in patients under 40 years of age in whom the disease had followed an acute or subacute course: in two of seven in this group corticoid treatment had previously failed. This fact, as well as the observation of exacerbations when immuno-suppressives were reduced, indicate the value of this form of treatment.


Purification, characterization and radioimmunoassay of thyrocalcitonin from rat thyroid glands. A highly purified preparation of rat thyrocalcitonin (TCT) has been obtained from lyophilized thyroid glands by gel chromatography following acid-acetone extraction. Biological activity of Sephadex G-50 eluates appeared in two peaks. The TCT in the major peak was concentrated, and applied to a Bio-Gel P-6 column, and a major protein peak was eluted which coincided with TCT activity. Potency, estimated by bioassay in rats, increase approximately 3500-fold from 0.075 MRC U/mg lyophilized glands to 250-400 MRC U/mg in the final product. The overall yield of TCT activity was about 36%. The purified product was characterized by chemical procedures and evaluated for its antigenic properties and use for radioimmunoassay. The purified rat TCT was used both labeled with 125I and as unlabeled standard. The following results were obtained: 1) Guinea pig antisera to either human or rat TCT were capable of binding 125I-rat TCT or 125I-human TCT; 2) Using either 125I-human or 125I-rat TCT and antisera to either TCT, pg amounts of rat and human TCT reacted in the assay while ng to mug amounts of salmon calcitonin or porcine TCT failed to react; 3) Using 125I-rat TCT and antisera to human or rat TCT, synthetic C-terminal (10-32 or 22-32) fragments of human TCT reacted well, while N-terminal (1-18) or desamide (1-32) derivatives reacted poorly or not at all; 4) Rat TCT was easily detected in normal thyroid venous plasma (5-10 ng/ml) and thyroid gland extracts (similar to 1 mug/gland) but not in peripheral blood; 5) Bioassay and radioimmunoassay of rat thyroid extracts (N equals 18) showed good agreement (r equals 0.86, p less than 0.001). The results support the idea that rat TCT is closely related to human TCT, indicate that major antigenic determinants reside in the C-terminal portion of the molecule, and show that antisera to either human or rat TCT can be used to measure rat TCT.


Staining banded human chromosomes with Romanovsky dyes: some practical consequences of the nature of the stain. Chromatographic analyses of commercial samples of Romanovsky stains were followed by various chemical and staining studies. Strong banding of chromosomes was found to be favoured by the presence in the stain of high concentrations of methylene violet Bernthsen and its immediate homologues. Chromatographic analysis showed that these dyes are present in dry Leishman and Giemsa powders only in small proportion. However, additional active dye may be generated during the process of making up staining solutions from the dry powders, if the methanol used is not contaminated with formic acid and if the period of heating is not too brief.


Bovine veneral vibriosis: antigenic variation of the bacterium during infection. Host parasite relationships in the female genital tract were studied in bovine venereal vibriosis by investigating agglutinin production and alterations in superficial antigens of the bacterium during the course of infection in two heifers. Cervicovaginal mucus (CVM) steamed cell agglutinins were shown to appear earlier and remain at consistently higher levels than whole-cell agglutinins. Whole-cell agglutinin titers fluctuated much more than steamed cell titers, suggesting possible changes in whole-cell antigens. Marked antigenic variation was demonstrated in successive monthly CVM isolates from the two heifers by agglutination tests with rabbit antisera of various specificities. Some changes in CVM antibody specificity during the infection were noted also. Antigenic variation in the bacterium was proposed as a mechanism for maintenance of the asymptomatic cervicovaginal carrier state in the presence of antibody.


Interaction of complex polysaccharides with the complement system: effect of calcium depletion on terminal component consumption. Complex polysaccharides and lipopolysaccharides can activate the terminal components of complement by either the classical (antibody, C1, C4, and C2) or alternative complement pathways, but the relative importance of either pathway for terminal component consumption in normal serum is poorly understood. Since classical complement pathway function requires both calcium and magnesium ions, whereas the alternative pathway requires only magnesium ions, selective chelation of calcium ions in serum can be used to block the classical complement pathway while leaving the alternative pathway intact. In these studies, ethyleneglycol-bis-(beta-aminoethyl ether)N, N-tetraacetic acid, a potent chelator or calcium, was used to block the classical complement pathway in normal guinea pig serum. Consumption of the terminal complement components by endotoxin, inulin, and zymosan in such serum was strikingly depressed when compared to serum containing an intact classical complement pathway. These studies demonstrate that in normal serum, both the classical and alternative complement pathways participate in the consumption of the terminal complement components by complex polysaccharides and lipopolysaccharides.


Antiglobulin factors in normal mouse serum reacting with enzyme-digested gamma globulin. The presence of antiglobulin factors in normal mouse serum was studied. Mice were injected with human 0 Rh(+) erythrocytes and the resulting gamma globulins were digested with papain. The reaction was demonstrated by agglutinations of human 0 Rh (+) perythryocytes sensitized with the Fab fragments when treated with normal mouse serum. Studies suggested that there are two factors in mice, a 7S AND A 19S globulin form. Cross-reactivity between strains of mice was demonstrated.


Slow axonal protein transport and visual function following retinal and optic nerve ischemia. Retinal ganglion cell protein synthesis and slow axonal protein flow have been measured in eight optic nerves from four macacus rhesus monkeys after producing ganglion cell ischemia. Comparison of the slow axonal protein flowing into the two optic nerves of the same control animal reveals a variability of up to 27 per cent. Following central retinal artery ligation, infarction of the retinal ganglion cells was reflected by a 97 per cent reduction in the radioactively labeled protein within the optic nerve. This profound reduction in labeled protein within the nerve confirmed that only ganglion cell dependent intra-axonal protein flow was being measured. Ischemia to the ganglion cell axons, with preservation of blood flow to the cell soma, was obtained in two optic nerves from different animals by severing all the posterior ciliary vessels entering about the optic nerve. Six weeks later, only a modest histologic loss of axons was present in these optic nerves. However, a profound reduction (up to 97 per cent) in labeled optic nerve protein was found at four days following intravitreal leucine injection. This is the time when the optic nerve slow axonal protein flow is dominated by the foveomacular ganglion cells. The reduction in slow axonal protein flow corresponds histologically to a preferential retrograde degeneration of the foveomacular ganglion cells, suggesting increased sensitivity of the smaller foveal axons to the induced ischemia. Electrophysiologic measurements support this conduction.


Medical treatment of prostatic obstruction. An objective assessment. Thirteen men suffering from prostatic obstruction were treated with an 8-week course of intramuscular injections of prostatic extract. Nine of these men had preliminary and subsequent evaluations of detrusor function and outflow obstruction by means of pressure/flow studies. Improvement in symptoms and measurements were only minimal and occurred in less than one-half of the cases. The greatest increase in flow rate recorded prostatectomy and no significant changes resulting from the injections could be seen on the histologic sections of their glands. These results did not confirm previous reports recommending this form of treatment for prostatic obstruction.