Effects of stimulus frequency on adaptation in auditory-nerve fibers. Several experimental methods of depressing the response of auditory-nerve fibers to tonal stimuli have been shown to reduce the response to signal frequencies at or near fiber CF (characteristic frequency) more than to frequencies greater or less than CF. In this study we have used a short adapting tone presented before each test-tone burst to reduce the fiber's response to the test tone. We observed the effects of changing test frequency when the adapting frequency was held constant at fiber CF. The depression in discharge rate was found to be approximately constant across test frequency.


Adaptation, saturation, and physiological masking in single auditory-nerve fibers. Results are reviewed concerning some effects, at a units's characteristic frequency, of a short-term conditioning stimulus on the responses to perstimulatory and poststimulatory test tones. A phenomenological equation is developed from the poststimulatory results and shown to be consistent with the perstimulatory results. According to the results and equation, the response to a test tone equals the unconditioned or unadapted response minus the decrement produced by adaptation to the conditioning tone. Furthermore, the decrement is proportional to the driven response to the conditioning tone and does not depend on sound intensity per se. The equation has a simple interpretation in terms of two processes in cascade--a static saturating nonlinearity followed by additive adaptation. Results are presented to show that this functional model is sufficient to account for the "physiological masking" produced by wide-band backgrounds. According to this interpretation, a sufficiently intense background produces saturation. Consequently, a superimposed test tone cause no change in response. In addition, when the onset of the background precedes the onset of the test tone, the total firing rate is reduced by adaptation. Evidence is reviewed concerning the possible correspondence between the variables in the model and intracellular events in the auditory periphery.


Sexual characteristics of preadolescent childrens' voices. This investigation was undertaken to enlarge current understanding of the acoustic properties which influence the perception of maleness and femaleness in the voices of prepubertal children. Perceptual judgments of sexual identity were obtained in response to tape recordings of whispered and normally phonated vowels, normally spoken sentences, and sentences spoken in a monotonous fashion. Seventy-three children provided recordings. The four utterance types were chosen to experimentally manipulate selected physical properties of speech thought to exert an influence on listener judgments of sexual identity. The results of this work suggest that cues stemming from differences in vocal tract dimensions and/or articulatory behaviors provided the primary cues about the sexual identity of these preadolescent children. Although laryngeal source cues could have provided relevant information about the sex of a few children, this variable was felt to play a relatively minor role in the sex recognition process. New information was uncovered about the role certain suprasegmental factors play in the identification of child sex.


Perceptual origins of the phoneme boundary effect and selective adaptation to speech: a signal detection theory analysis. Differences in discriminability of stimuli near phoneme boundaries and findings from selective adaptation have been used to argue for the existence of neurophysiological mechanisms--feature detectors--which mediate the perception of speech and speechlike sounds. A detection theory model was used in order to discover whether or not the phoneme boundary effect and the shift in phoneme boundary after adaptation might rather be attributable to changes in response bias. This model was applied in the analysis of phoneme identifications of three sets of stimuli before and after adaptation. While the origins for the phoneme boundary effect appear to lie below the level of response bias, findings suggest that identification changes after adaptation may be due solely to shifts in criterion, rather than changes at the sensory level.


Developmental study of vowel formant frequencies in an imitation task. Imitations of ten synthesized vowels were recorded from 33 speakers including men, women, and children. The first three formant frequencies of the imitations were estimated from spectrograms and considered with respect to developmental patterns in vowel formant structure, uniform scale factors for vowel normalization, and formant variability. Strong linear effects were observed in the group data for imitations of most of the English vowels studied, and straight lines passing through the origin provided a satisfactory fit to linear F1--F2 plots of the English vowel data. Logarithmic transformations of the formant frequencies helped substantially to equalize the dispersion of the group data for different vowels, but formant scale factors were observed to vary somewhat with both formant number and vowel identity. Variability of formant frequency was least for F1 (s.d. of 60 Hz or less for English vowels of adult males) and about equal for F2 and F3 (s.d. of 100 Hz or less for English vowels of adult males).


Cochlear action potential threshold and single unit thresholds. There is a close correlation between the sound pressure of tone burst required to affect a primary auditory neuron at its characteristic frequency and that which will produce a detectable N1 response at the same frequency. Units with thresholds from 80--0 db SPL (recorded from damaged and undamaged cochleas) were 0--20 dB , respectively, more sensitive than the action potential response.


Influence of earphone-cushion center-hole diameter on the acoustic output of audiometric earphones. Although the dimensions of the MX-41/AR earphone cushion are specified in ANSI S3.6--1969, nonstandard MX--41/AR cushions are still found on some audiometers. Variations in the diameter of the cushion's center hole are shown to affect the coupler calibration of the earphone and also hearing threshold measurements at high audiometric frequencies.


The effect of bone conduction on the intensity independence of dichotic chords. The relative salience of the pitch components of a two-tone dichotic chord is invariant with respect to the relative intensity of the two tones over a wide range of interaural intensity differences [R. Efron and E. W. Yund, J. Acoust, Soc. Am. 889--898 (1976)]. According to a recently developed model, the range of intensity independence is limited by the bone-conducted energy from the more intense tone [E. W. Yund and R. Efron, J. Acoust. Soc. Am. 62, 607--617 (1977)]. The model predicts that a decrease in bone conduction such as the one achieved by using insertion earphones, must increase the range of intensity independence. This prediction is confirmed.


Control of vasospasm following trauma and microvascular surgery. Vasospasm may result in marked reduction of blood flow through injured or revascularized tissues. Neurogenic vasoconstriction is mediated through sympathetic pathways which may be blocked by long-acting local anesthetics resulting in optimal intravascular pressures and elevated flow. An experimental study performed on normal human volunteers has shown that distal sympathetic blockade using Bupivacaine protects the digital circulation against vasospasm elicited by a strong stimulus for a minimum of 7 to 8 hours. A catheter, placed adjacent to the median or ulnar nerve at the wrist level after digital microvascular reconstruction, facilitates continuous Bupivacaine sympathetic blockade. This technique has been used clinically and appears to improve the circulation of replanted or revascularized tissues and protects against vasospasm caused by a variety of stimuli.


Prevention of femoral vein occlusion by local injection of Thrombolysin in the rat. An experimental model was developed that will produce femoral vein occlusion greater than 90% of the time in rats weighing less than 500 grams. This standard venous clot, produced by combining intimal trauma with local venous stasis, can simulate clinical crush and replantation problems. Using this standard clot model, Thrombolysin was injected in the femoral artery after trauma to the vein but before venous stasis. Femoral vein patency was determined at the end of the 30 minute period of venous stasis. With the appropriate dosage, ipsilateral venous occlusion was prevented (P less than 0.00001) without preventing contralateral venous occlusion (P less than 0.02). Except for decreased fibrinogen levels, there was no significant change in the factors studied between the control and experimental groups. It is possible, therefore, to prevent thrombosis in a vein with intimal damage, even in the presence of a low-flow state by the local injection of Thrombolysin, without producing systemic anticoagulation.


A complex reimplantation of digits: a case report. In multiple finger amputations, microsurgical reconstruction should concentrate on the thumb, index, and middle fingers. The patient in the case report presented in this paper initially sustained an amputation of all of the digits on the left hand and an amputation of the right thumb. Both thumbs were amputated at the metacarpophalangeal joint. Initial replantation of the left thumb, index, and middle fingers and of the right thumb was carried out. The right thumb replantation failed and, after healing, the right great toe was transferred to the right hand. Subsequent to this, the patient developed useful function of all reconstructed digits. Twenty-one months after the first injury, both thumbs sustained new traumatic amputations 1.0 cm distal to the previous amputations. Both thumbs were replanted again successfully.


Lipofibroma of the median nerve.

Lipofibroma of the median nerve. Tumors arising within the median nerve in the region of the distal forearm, wrist, and palm are rare and their exact pathological nature has not been well clarified. One case is reported in a 47-year-old woman, in whom a mass of 3 years' duration was located in the thenar eminence of the right hand without causing any sensory or motor deficit. The tumor was surgically excised, and the continuity of the nerve branches was preserved. The diagnosis of lipofibroma of the median nerve is recommended for this entity. Other pathological lesions of the median nerve are mentioned.


Prevention of extensor lag after indicis proprius tendon transfer. An experiment on fresh cadaver hands showed that a longitudinal incision of the hood did not affect index extension when traction was made on the common extensor tendon, but that excision of a portion of the hood containing the indicis proprius caused an extensor lag. The lag was eliminated by repair of the hood, providing that the closure was not too tight to prevent normal excursion of the hood. These findings were correlated with findings in patients who had undergone indicis proprius tendon transfer. Extensor lag after indicis proprius transfer is not caused by removal of the force of the tendon per se, but by factors which cause either disruption of normal hood function or tethering of its normal excursion.


Locking of the metacarpophalangeal joint: a case report. A case of an unusual cause of locking of the finger is described. This was brought about by the presence of an exostosis arising from the metacarpal bone, causing rupture of the capsule of the metacarpophalangeal joint with entrapment of the interosseus tendon.


Entrapment neuropathy due to bilateral epitrochleoanconeus muscles: a case report. A case of bilateral entrapment of the ulnar nerves due to accessory epitrochleoanconeus muscles was observed in a young athlete. Hypertrophy of this muscle may be one of the causes of cubital tunnel syndrome.


Another cause of median nerve compression by a lumbrical muscle in the carpal tunnel. A case is described in which division of a flexor digitorum profundus tendon allowed the proximal end of the tendon to retract, drawing its lumbrical muscle into the carpal tunnel where it caused compression of the median nerve.


Life changes and menstrual discomfort.

Life changes and menstrual discomfort. The present study addressed the relationship between the accumulation of life changes and problems with menstruation. Female college students completed a Life Experiences Survey, which assesses desirable and undesirable life changes, and a menstruation questionnaire, which contains items relevant to menstrual discomfort and irregularity. Correlational analyses showed that undersirable life changes were correlated with reports of number of symptoms of menstrual discomfort, but not irregularity. Separate analyses among oral contraceptive users and nonusers showed that the relationship between life changes and menstrual discomfort occurred only among nonusers. A regression of contraceptive use, desirable life changes, and undersirable life changes on factors derived from the menstruation questionnaire indicated that undesirable life changes was the strongest predictor of menstrual problems.


Nutrition and breast cancer.

Nutrition and breast cancer. Present evidence suggests that a high fat intake may be one of the factors in the aetiology of breast cancer. Patients with breast cancer may show an increased requirement for thiamin particularly when treated with 5-fluorouracil, and a number of metabolic disturbances in which ascorbic acid may play a central role.


Vitamin A and cancer of epithelial origin. Animal studies have shown. a) an association between vitamin A and cancers of epithelial origin, and b) that vitamin A and its analogues delay tumour appearance, retard tumour growth and regress tumours induced by carcinogenic polycyclic aromatic hydrocarbons. Human epidemiological and biochemical studies suggest that cancers of epithelial origin may be associated with vitamin A deficiency. Vitamin A and its analogues may have a prophylactic and a therapeutic role in cancers of epithelial origin.


The nutritional status of poor children in London. Concern for the growth and development of poor inner-city children prompted an investigation of the relationship of growth to diet, health and sociological background. Between 1973 and 1976, 1000 households in poor areas of London were screened for at-risk children between the ages of one and 12 years. Two hundred and thirty-one children from 112 families qualified for the survey. Of the white children, 21 per cent fell below the 10th percentile for height. The mean energy intake of the shortest children was 72 per cent of the RDI. Half the families spent 4.80 pounds or less per person per week on food, and 33 per cent of the children fell below the 10th percentile for height. A remedial feeding programme may be of benefit to these and similar children.


The resilience of British household diets during the 1970s. The 1979s saw rapid increases in prices, including food prices, but incomes also increased rapidly. Many other factors, such as the growth in home-freezer ownership, could also have affected dietary habits. Yet the National Food Survey shows that although less food is now bought for use in the home (9.5 MJ/person/day compared with 10.7 MJ in 1970), the overall distribution of the diet between meat, fish, dairy products, cereals, sugar, fats, fruit and vegetables remained comparatively steady. Greater changes in consumption of foods within the same broad groups had little effect on overall nutrient intakes, so that the nutritional quality of the diet (measured as nutrients/MJ) actually increased.


A prudent diet for the nation.

A prudent diet for the nation. Nutritional factors in the aetiology of coronary heart disease, maturity-onset diabetes, diverticular disease and dental caries are discussed. Four principles for a prudent diet are suggested, namely: avoid excess intake of energy, increase dietary fibre intake, reduce total fat intake to approximately 30 per cent of energy intake, take a high proportion of fat as the polyunsaturated form.


Nutrition education for changes.

Nutrition education for changes. Nutrition education aims to change behaviour. Educators must consider the circumstances of those they seek to educate. Methods need constant evaluation. Salient points from 16 recent reports of evaluation are set out.


Lymphocyte-mediated cytotoxicity microassay by cytofluorography. A cytofluorometric method for measuring lymphocyte-mediated cytotoxicity is described which employs acridine orange and ethidium bromide stains. These stains permits the rapid (approximately 45 sec per sample) differential enumeration of viable cells and are therefore valuable in the preparation and performance of a cytotoxicity assay. Reproducibility of viable target cell counts is good and, statistically, the same mean result is obtained when the cytofluorometric and an accepted radioisotopic method are compared. It is found that the method employing radioisotopic label ([125I]iododeoxyuridine) non-specifically killed 80% of the target cells, whereas the cytofluorographic method does not result in non-specific kill. Therefore, the cytofluorometric method reflects in vivo conditions more accurately. The cytofluorometric method also provides a more rapid and less technically demanding assay than those previously described.


HLA-D typing of human lymphocytes using frozen and thawed spermatozoa. A method is described for the preservation of haploid populations of human spermatozoa in liquid nitrogen for their subsequent use as stimulators in HLA-D (SL) lymphocyte typing. The typing results obtained using thawed spermatozoa correlated well with those obtained when using fresh sperm and also with other cellular typing methods.


The identification of the subclasses of human IgG by analytical isotachophoresis. A new method is described for demonstrating the individual subclasses of human IgG immunoglobulins by means of analytical isotachophoresis. Individual subclasses of IgG purified from sera of multiple myeloma patients have distinct mobility patterns. When a mixture with purified IgG for each of the 4 subclasses is analyzed, a characteristic mobility pattern with 4 unique peaks is obtained. An IgG of unknown subclass can be identified by the superimposition of the peak for the unknown upon one of the 4 well characterized peaks. The method using microgram quantities protein in a 1.0 microliter volume can be performed easily in 15 min.


The use of [125I]C1q subcomponent for the measurement of complement binding antibodies on cell surfaces. An assay using 125I-labelled human C1q has been developed for the measurement of complement fixing antibodies bound to cell monolayers or cell suspensions. The method has been adapted for use either during or after sensitisation of the cells with antiserum, is simple to perform and does not require require prelabelling of the target cells.


Induction, isolation and surface marker studies on bovine eosinophils. A crude extract from Ascaris suum was infused into the teat canal of heifers to serve as an irritant or an antigens. The cells present in the mammary gland following such stimulation were assessed over a period of 2 weeks. Prior to stimulation there were few cells, predominantly macrophages, however, by 12 h post-stimulation a larger number of eosinophils and neutrophils were present. The eosinophils, which represented approximately 50% of the total population, could be purified by Ficoll-Hypaque flotation and nylon or glass wool column filtration to yield a population consisting of over 90% eosinophils. Surface marker studies on the purified eosinophils revealed that they contained both Fc and complement receptors.


Avian antigen binding cells: enrichment methods. Data are presented comparing different methods for the fractionation and enrichment, respectively, of specific antigen binding lymphoid cells from immunized chickens. The bovine serum albumin (BSA) anti-BSA system was chosen as a model. To enrich avian antigen binding cells (ABC) from a mixture of chicken peripheral blood and spleen lymphocytes 3 different methods were used: (1) separation of cells forming rosettes with antigen-coated sheep red blood cells (SRBC) from non-rosetting cells by density centrifugation; (2) isolation of ABC by their specific adherence to antigen bound to immunoadsorptive surfaces (gelatin, plastics); (3) column affinity chromatography with antigen-coated agarose, cross-linked dextran for plastic beads. The most efficient method was column affinity chromatography with antigen-coated polyacrylamide beads which affords up to 12-fold enrichment of ABC. Both the other methods are also suitable for separation and enrichment of specific ABC but can only with difficulty be adapted for processing the large numbers of cells which would be necessary, e.g., for in vivo transfer studies.


A simple radiolabelled rheumatoid factor binding assay for the measurement of circulating immune complexes. A simple assay for circulating immune complexes has been developed and the optimal conditions for reaction defined. Partially purified radiolabelled polyclonal or monoclonal rheumatoid factor was incubated with aggregated IgG or soluble immune complexes and the resultant macromolecule precipitated with 3% polyethylene glycol. Monoclonal rheumatoid factor was much the better reagent, allowing the detection of approx. 0.35microgram/ml or more of aggregated IgG. Soluble immune complexes formed in vitro at between x2--x20 antigen excess were detectable over a wide range of molecular size. Clinical studies indicated that the assay is a useful addition to the currently available techniques for measuring circulating immune complexes.


A new method of testing for mitogen-induced lymphocyte stimulation: measurement of the percentage of growing cells and of some aspects of their cell kinetics with an electronic particle counter. Human lymphocytes were cultured with or without added PHA for periods not exceeding one day so that none of the cells had entered the first mitotic division. The size distribution of the cells was measured with an electronic particle counter and the results were collected in a multichannel analyser. An iterative stochastic model was developed to estimate the proportion of responding cells and their growth characteristics. This mathematical model was based on a few simple assumptions about the pattern of cell growth and was considered to fulfill basic requirements of plausibility and parsimony. The technique described in this paper makes measurement of the absolute percentage of responding cells and their average growth rate in mitogen-induced lymphocyte stimulation tests possible in routine diagnostic laboratories for the first time.


Inhibition of murine natural killer cell-mediated cytotoxicity by pretreatment with ammonium chloride. In the present study the effect of ammonium chloride on murine natural killer (NK) cell-mediated cytotoxicity to T cell lymphoma, YAC-1 was studied. It was found that ammonium chloride treatment significantly reduced the cytotoxicity of splenic NK cells without any detectable change in cell viability. It is, therefore, suggested to avoid ammonium chloride treatment in order to obtain the realistic reflection of murine NK cell activities.


Chemotaxis in Boyden's chamber: a comparison of the double and single filter techniques. In the Boyden's chamber method to assess chemotaxis, when used to detect drug induced impairment of chemotaxis, the double filter counting method shows no advantage over the single filter technique.


The aerobic growth of Propionibacterium acnes in primary cultures from skin. Although Propionibacterium acnes ordinarily grows as an anaerobe, this organism was commonly seen on aerobic primary cultures (directly from skin) of the forehead, axilla, deltoid area, and antecubital fossa. On subculture, strains from aerobic primary cultures showed their normal anaerobic state. On repeated tests of the foreheads of 7 subjects over periods of 1 to 4 yr, 24% of all cultures were positive for propionibacteria (P. acnes) on aerobic culture. This phenomenon was equally common in cultures from those with relatively sparse or dense populations of P. acnes on the skin surface. Several different patterns of aerobic growth were observed: satellitism, profuse growth at one dilution and none on the next higher dilution, and proportionate growth in successive dilutions. These different growth patterns indicate that more than one mechanism is operative in stimulating the aerobic growth of propionibacteria. Whether one or more of these mechanisms is operative in vivo, we do not know, but it appears that they do not account for the great individual differences in population density of P. acnes on such sites as the forehead.


Significance of levels of specific immunoglobulins to DNA in SLE patients' sera detected by solid phase radioimmunoassay. A solid phase radioimmunoassay was developed for detecting the quantity of double-stranded and single-stranded DNA antibodies in patients with systemic lupus erythematosus and other connective tissue diseases. The assay system employs a solid support 96-well, flex-vinyl microtiter plate to which bovine methyl albumin is layered, followed by denatured or native calf thymus DNA. A 1:80 dilution of patients' sera was added to respective wells followed by tritiated high affinity anti-IgG, -IgA, or IgM. Denatured DNA (single-stranded DNA) bound to methylated bovine serum albumin had less than 5% reannealment to the double-stranded form and provided a better substrate for Ab binding than double-stranded DNA, producing a linear binding curve. Of 58 patients diagnosed as having systemic lupus erythematosus (SLE), only 11 having active SLE had IgG antibody levels of greater than 5.0 microgram/ml to single-strand DNA. Renal involvement of some degree was found in all 11 with the high concentrations of IgG antibodies to DNA correlating with severe involvement. Patients with IgM antibodies to DNA alone had more benign types of SLE with little renal involvement. No abnormal levels of IgA Ab to either single-strand DNA or double-strand DNA were found in SLE patients' sera. Corticosteroid and/or immunosuppressant treatment caused a marked drop in the IgM Ab level to DNA within 10 days while IgG Ab to DNA remained high for up to 30 days. Quantitation of IgG and IgM Ab to single-strand DNA provides a useful method for diagnosing severe SLE with possible renal involvement and monitoring the course of the disease during therapy.


Ultraviolet radiation-induced inflammation and leukocytes. To evaluate the role of leukocytes in inflammation induced by ultraviolet radiation, the response of guinea pigs make leukopenic with cyclophosphamide was compared with the response of nonleukopenic animals. The response of leukopenic animals to UVB (295 nm) was significantly altered. Leukopenic animals and saline-treated (i.e., nonleukopenic) animals responded similarly to (1) UVC (250 nm), (2) UVA (340 nm) given after 8-methoxypsoralen pretreatment (PUVA), (3) intradermal histamine and (4) a topically applied prostaglandin analogue. These results suggest that leukocytes are important in UVB-induced inflammation but not in the inflammation induced by UVC or PUVA.


Effect of 8-methoxypsoralen plus UVA on psoriasis leukotactic factor. The effect of psoralen phototherapy on the chemotactic activity of psoriasis leukotactic factor (PLF) was studied. The chemotactic activity of PLF extracted from psoriasis scales was evaluated using modified Boyden chambers. Treatment of (1) psoriasis lesions, (2) psoriasis scale and (3) extracted PLF with 8-methoxypsoralen plus UVA irradiation reduced the chemotactic activity of PLF. These results may help define the mechanism of psoralen phototherapy in psoriasis.


Selective toxicity of 6-hydroxydopa for melanoma cells. The growth inhibitory effect of 6-hydroxydopa, a cytotoxic analog of L-dopa, was studied in melanotic and amelanotic Cloudman melanoma, mouse fibroblast L929 and Chinese hamster ovary cells. A marked sensitivity of pigmented cells to 6-hydroxydopa was observed with a 10-fold increase in sensitivity of pigmented cells. Sensitivity correlated with the capacity of cells to incorporate radiolabeled exogenous L-dopa. The drug affected primarily DNA and RNA synthesis with greater inhibition observed in pigmented cells than the nonpigmented control cells. The mechanism of action may involve interaction with the melanocyte specific enzyme, tyrosinase, as a false substrate.


Colloid-amyloid bodies in PUVA-treated human psoriatic patients. In 4 cases of PUVA-treated psoriatic patients a number of colloid bodies and amyloid-like deposits were seen at the dermo-epidermal junction, in a very similar fashion the colloid bodies and the amyloid substances are deposited in lichen planus and in primary cutaneous anyloidoses respectively. In some instances such a deposition was found within the epidermis and contained remnants of cellular debris. Serial sections revealed that a part of the intraepidermal deposit is located in the dermis. Some deposition is partially composed of typical amyloid filaments and partially of nonamyloidal filaments. The latter were identical to those found in colloid or Civatte bodies of lichen planus and other conditions. Follow-up biopsies done in 1 patient several months after the cessation of the treatment still showed these substances. It was suggested that the amyloid-like substances are the product of special degeneration (apoptosis) of epidermal cells as colloid substances: Initally these cells undergo filamentous or colloid degeneration and they drop off into the dermis; where some of the characteristics of filaments are modified and connective tissue elements are added to produce such filamentous and amorphous components as seen in the amyloid island, whereas others remain as colloid bodies. Absorption or elimination of these substances seem to be extremely slow.


Culture of normal human epidermal cells with 3T3 feeders on millipore filters. Human epidermal cells were cultured with lethally irradiated 3T3 cells and grew as large colonies both on plastic and millipore filters. Subcultures were possible. The grown colonies were studied morphologically and histologically. The whole intact crossview of epidermal colonies in paraffin sections was obtained from the cell culture on millipore filters. The epidermal cells derived from younger persons had higher efficiency of colony formation than those from older ones. The membrane filter was shown to be good substratum for epidermal cell growth as well as plastic.


Growth and differentiation of postembryonic mouse epidermal cells in explant cultures. Until now the only successful growth of postembryonic skin in explant cultures has been with human skin. We describe the successful cultivation of postembryonic mouse skin explant culture in this report. We believe that any adult skin can be grown in explant culture.


Skin responses to ultraviolet radiation in contact photodermatitis due to fentichlor. There are several groups of chemicals that may produce contact photodermatitis and the action spectra for photopatch tests with these chemicals have been established. Controversy exists about UVR sensitivity in patients with contact photodermatitis when tests are performed on normal appearing skin without the addition of the chemical. Four patients became "persistent light reactors" after developing contact photodermatitis from fentichlor, 3 after using a hair cream containing the chemical, the 4th after industrial exposure. Normal appearing skin on the back of the trunk was tested to narrow waveband UVR and visible light, fentichlor was not added to the skin during these tests. Abnormal reactions to UVB occurred in all 4 patients and all showed sensitivity to UVA, to 340 nm in 1, to 360 nm in 1 and to 400 nm in 2. At pH 4 fentichlor absorbed between 310 nm and 325 nm, but at pH 9.2 absorption was between 275 nm and 350 nm, there was no absorption above 350 nm. The results of tests with narrow waveband UVR show that true sensitivity to UVB does exist in the normal appearing skin of "persistent light reactors," the sensitivity is not spurious. The normal skin of these patients is also sensitive to UVA. Possible reasons for the URV sensitivity are discussed.


Sebaceous gland differentiation. I. Separation, morphology and lipogenesis of isolated cells from the mouse preputial gland tumor. Single cell suspensions have been prepared, by enzyme digestion, from the mouse preputial gland tumor and separated by flotation centrifugation into populations of different buoyant densities. These populations of cells have been shown by morphological, chemical and biochemical criteria to be in different stages of maturation. Some properties of the separated cells are described.


Interactions of Trichophyton mentagrophytes and micrococci on skin culture. Scanning electron microscopy was used to search for local or limited synthesis of antibiotics by a strain of Trichophyton mentagrophytes. Micrococcus luteus, which was susceptible to penicillin and to the dermatophyte when both were cultured on agar media, displayed morphological alterations of flattened walls, invagination, enlargement, and collapse in skin cultures with the fungus. Penicillinase did not neutralize these effects. A control strain of Staphylococcus spp with poor sensitivity to penicillin was resistant to the dermatophyte in all test systems. T. mentagrophytes showed positive tropism to the bacteria. Regional variation in fungal germination and antibiotic production, the limited yield of antibiotics, and the pattern of dermatophyte growth and alteration of bacterial morphology demonstrated the significant influence of microenvironment on antibiosis.


Crosslink of collagen in hypertrophic scar. It is conceivable that intramolecular and intermolecular crosslinks of collagen may be involved in the formation of hypertrophic scar, but little is known about the relationship between hypertrophic scar and crosslinks of collagen. We have isolated a new crosslinking amino acid from collagen and have named it pyridinoline. In this investigation, we examined the content of pyridinoline in human normal skin, mature scar and hypertrophic scar. An appreciable amount of pyridinoline was found in collagen of hypertrophic scar, but pyridinoline is virtually absent in collagen of normal skin.


Interactions between centrally and peripherally generated neuromuscular oscillations. An experimentally based model of the mammalian neuromuscular system has been extended to include the interaction of sinusoidal inputs generated within the central nervous system and those produced peripherally by reflex pathways, together with muscle properties and external loads. Multiple reflex pathways and pathways having acceleration as well as velocity and length sensitivity and considered. The responses are analyzed for brief inputs (Dirac delta-functions), sinusoidal driving functions and mixtures of the two over ranges in which the model behaves either linearly or non-linearly. Approximate solutions are derived for the non-linear range, and exact numerical solutions are computed for a few examples within the linear range. The extent to which brief inputs can reset ongoing oscillations and the extent to which sinusoidal inputs can entrain these oscillations are of particular interest.


Hysteresis, oscillations, and pattern formation in realistic immobilized enzyme systems. Hysteresis, oscillations, and pattern formation in realistic biochemical systems governed by P.D.E.s are considered from both numerical and mathematical points of view. Analysis of multiple steady states in the case of hysteresis, and bifurcation theory in the cases of oscillations and pattern formation, account for the observed numerical results. The possibility to realize these systems experimentally is their main interest, thus bringing further arguments in favor of theories explaining basic biological phenomena by diffusion and reaction.


A functional model of the rat kidney.

A functional model of the rat kidney. A mathematical model of the nephron was developed by writing a set of material balance equations for the flow of urea, salt and water along the foregoing study and are taken here as a basis, in particular the model configuration of the collecting duct system. The stimulation of the model equatentration profiles which at the ends of the several tubular sections were consistent with the values observed in experimental investigations.e medullary interstitial solute concentration profiles are taken to increase linearly in outer and inner zone. The several transeptithelial fluxes are driven by diffusion, osmosis, solvent drag and active transport. The development of osmotic gradient in the inner medulla is taken here to be caused by active secretion of salt into the descending LImb of Henle's loop. The parameters in the flux equations for all parts of the nephron and the concentration values at the end of each tubular section are determined by collecting and averaging the values given in literature and by extrapolating the measurement data. The simulation of the model equations with these averaged parameters resulted in concentration profiles which at the ends of the several tubular sections were consistent with the values observed in experimental investigations.


Superiority of 24-hour outpatient monitoring over multi-stage exercise testing for the evaluation of syncope. Twenty-four hour outpatient monitoring was compared with maximum multi-stage Treadmill exercise testing for the detection of dysrhythmias producing syncope or near syncope in 119 patients. All patients had cardiovascular disorders; only 21% had coronary artery disease. Patients with obvious cause of syncope and/or significant dysrhythmias by resting electrocardiograms (ECGs) were excluded. A significant dysrhythmia was found which was considered the probable cause of syncope or pre-syncope in 76 patients (64%). A non-cardiac cause was found in tachycardia, exercise testing identified only patients with complex ventricular dysrhythmias and missed 64% of these. Overall, dysrhythmias were found by ambulatory monitoring alone in 63 patients, by exercise testing alone in only three, and by both in 10. It is concluded that: 1) in the majority of patients with syncope or pre-syncope suspected to be of a cardiac origin, a dysrhythmia can be found; 2) ambulatory monitoring is far superior to exercise testing for detection of dysrhythmias; 3) exercise testing increases the yield for complex ventricular dysrhythmias.


Electrocardiographic poor R wave progression. II: correlation with angiography. Forty patients with "poor R wave progression" (PRWP) or "reversed R wave progression" (RRWP) on the electrocardiogram (ECG) who underwent coronary arteriography and left ventriculography within one month of electrocardiographic recording were analyzed. Patients were randomly selected from a population of catheterization proven predominant mitral stenosis with elevated right ventricular pressures (presumed right ventricular hypertrophy), predominant aortic stenosis with increased left ventricular mass (left ventricular hypertrophy) and anterior myocardial infarction (AMI). Application of criteria previously derived from vectorcardiographic (VCG) correlative data, as well as inclusion of right precordial lead repolarization abnormalities, correctly diagnosed 85% (11/13) of angiographic AMIs. It is clinically useful to note that 56% (15/27) of patients with either PRWP or RRWP who did not exhibit angiographic AMI could be identified by 12 lead ECG with only 12% (2/17) false negative AMIs. In comparison with Q wave anterior myocardial infarctions, those with only PRWP or RRWP exhibited a trend toward a less severe degree of contraction abnormality on contrast ventriculography.


Prolongation of the Q-T interval in lithium toxicity. A patient with lithium intoxication and Q-T prolongation is described. As serum lithium levels fell with therapy, serial electrocardiograms (ECGs) demonstrated T wave changes more commonly associated with lithium. All changes were ultimately reversible.


Alternation of partial and total atrial standstill. A forty-five year old man with longstanding rheumatic heart disease whose surface electrocardiogram (ECG) showed absent P waves and two alternating QRS complex rhythms, one regular and the other irregular, was submitted to electrophysiological studies. For regular QRS complex rhythm these studies revealed (1) presence of total and bilateral atrial standstill and (2) regular ventricular rhythm originating in the A-V junction; while for irregular QRS complex rhythm the studies showed (1) presence of atrial standstill in the area of the upper right atrium, and (2) a +/- 150/min atrial activity rate in the intracavitary and esophageal electrogram and a +/- 300/min rate in the epicardial mapping. The spread of conduction of this atrial activity indicates that it originated within an atrial area near the tricuspid valve. The presence of an alternating partial and total atrial standstill is a unique feature which to data has not been reported in the literature.


Computer simulation of ventricular tachyarrhythmias during coronary artery ligation and release. A computer (PDP-10) simulation model was constructed using rapid, simultaneous measurements of effective refractory period (ERP), ERP dispersion (RPD), premature ventricular beat (PVB) thresholds, and multi-directional conduction times during coronary artery ligations and release in the anesthetized dog. In addition, estimates of currents of injury between ischemic and non-ischemic electrodes were included based on published data from electromagnetic recordings in dogs. Propagated PVB's were inscribed by the model when criteria for excitation, dispersion, and conduction were met based on known electrophysiological characteristics of heart muscle. The model correctly predicts high vulnerability to arrhythmias at three to seven minutes of ligation, stabilization at 10 to 15 minutes of ligation, and decreased vulnerability by lidocaine during ischemia. There was no arrhythmia when ischemic thresholds were increased by the drug before significant RPD and conduction prolongation developed. Vulnerability to arrhythmias was also predicted by the model after release of short (five minute) and long (15 minute) ligation. Since (experimentally) arrhythmias occurred much more frequently after long ligations, additional yet unknown factors other than those considered in the model must be operative in the genesis of reperfusion arrhythmias. This conclusion is supported by the observations that high ischemic thresholds induced by lidocaine returned to normal slowly after ligation release, and despite this protective effect, experimentally, lidocaine failed to abolish reperfusion arrhythmias.


Further development of a model for electrical transmission between myocardial cells not connected by low-resistance pathways. We previously described a model for the electrical transfer of excitation from one cell to the next which utilized the electric field generated in the cleft between the cells. This model was analyzed only for the steady-state condition. In the present paper, we calculate the effects of membrane capacitance on the transmission of an action potential between two adjacent cardiac cells; the junction between cells was composed of two high-resistance excitable membranes separated by a narrow cleft. The parameters varied for this study included the threshold potential and capacitance of the junctional membranes. The calculations indicate that it is somewhat easier to achieve transmission when capacitive effects are included. Thus, the electric field model provides an alternative means of cell-to-cell propagation between myocardial cells which is electrical in nature but does not require the presence of low-resistance connections between cells.


ST isopotential precordial surface maps in patients with acute myocardial infarction. ST amplitude distributions were studied in 41 patients with acute myocardial infarction by deriving isopotential maps from a 5 x 7 electrode precordial matrix. Independent data on infarct size and localization were obtained utilizing the technetium 99m stannous pyrophosphate scintigraphic method. The locus of maximal ST elevation was stable for at least two days in 86% of 27 patients with anterior infarction. A single maximum or maximum-minimum was found in 88% but 22% of the patients had multiple maxima and/or minima in at least two maps. Areas of significant ST elevation were often excluded from the precordial matrix. The site of maximal ST elevation correlated with scintigraphic infarct site but was displaced medially in lateral infarction. The relation between infarct size and sigmaST elevation was significant and curvilinear. sigmaST underestimated size in large anterior infarction. The correlation of the size and the number of sites with ST elevation greater than or equal to 1.5 mm was weak (r = 0.56). The degree of ST abnormality in 14 patients with inferior infarction decreased significantly during the initial 24 hours. The isopotential maps were similar to those obtained in anterior infarction but the polarity was reversed. The results provide limited support for the continued exploration of ST analysis as a clinical method but suggest that sizing methods should be based on total body surface mapping, taking into account the geometry and electrical properties of the torso.


Transfer of coupling of premature ventricular contractions to an ectopic ventricular tachycardia: a mechanism for atypical bidirectional tachycardia. Bidirectional tachycardia was observed on Holter tracings recorded from a dog three days after the production of a small freeze lesion on the wall of the left ventricle. A bigeminal rhythm with fixed coupling of ventricular premature contractions was interrupted by a burst of ventricular tachycardia of different morphology. The ventricular premature contractions, originally coupled to the sinus beats, became coupled to the new ventricular tachycardia with an identical coupling interval. This resulted in a dibirectional tachycardia, created by the "transfer" of coupling of premature ventricular contractions to a separate ectopic ventricular tachycardia.


Quantification of the Frank and McFee-Parungao orthogonal electrocardiogram in valvular pulmonic stenosis. Correlations with hemodynamic measurement. In 66 patients with congenital valvular pulmonic stenosis and intact ventricular septum, correlations were obtined among various multiple hemodynamic and orthogonal vectorcardiographic parameters. The Frank and McFee-parungao lead systems were used. The most important hemodynamic parameter evaluated was right ventricular pressure (RVP). RVP correlated best with X terminal to the right (XTR) in both Frank (R = 0.68) and McFee (R = 0.61) systems. The correlation between RVP and Z anterior was poor. The direction of the initial QRS vector on the X axis was helpful in predicting severity. With X initial to the right, especially in McFee, the RVP is most likely to be systemic or less, while with X initial to the left, the RVP is frequently but not necessarily suprasystemic. T vector spatial orientation is not helpful in the assessment of severity.


Effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker in awake dogs. The effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker was evaluated in 15 awake dogs with experimentally induced A-V junctional rhythm. The duration of asystole after overdrive (D.A.O.) in these dogs was prolonged significantly in accordance with increase in the drive rate, and the mean +/- SD of the D.A.O. reached 4.7 +/- 1.1 seconds (N = 15) after overdrive at 2.5 times the spontaneous heart rate. After administration of atropine (0.4 mg/kg; i.v.) to eight dogs, the mean +/- SD of the D.A.O. at the same rate decreased from 4.5 +/- 0.9 to 3.4 +/- 1.2 seconds. After administration of practolol (0.5 mg/kg; i.v.) to the seven other dogs, the mean +/- SD of the D.A.O. at the same rate increased remarkably from 4.9 +/- 1.3 to 9.4 +/- 3.0 seconds. Intravenous injection of practolol (0.5 mg/kg) had no effect upon the D.A.O. in the five dogs with sinus rhythm. Thus, it is suggested that (1) the sympathetic nerve might play a more important role in regulating the automaticity of the A-V junctional pacemaker than the vagus and (2) it physiologically might take over 5.0 seconds for the A-V junctional pacemaker to initiate an escape beat during longstanding sinus arrest, if a marked dysfunction of the A-V junctional pacemaker occurs due to a decrease in tension of the sympathetic nerve.


Clinical importance of directional statistics for electrocardiographic differentiation of smoking habits. Statistical methods for the analysis of directional data are of relatively recent origin and have not been generally applied in clinical investigations where they are appropriate. This study compares spherical means and standard deviations for directional polarcardiographic variables with the linear means and standard deviations of the same variables for a typical industrial cohort of male white collar workers. Normal subjects were classified by smoking status and by independent clinical evidence of the presence of CHD, and both directional and linear statistics are applied to compare the PCG variables in these groups. Directional statistics more accurately define the spherical means and variances of heart vectors and thereby permit more reliable differentiation of directions, or angles to aid diagnosis.


The mitochondrial activation of sulfate and arsenate and their role in carcinogenesis. Sulfate substitutes for phosphate in the transitory uncoupling of rat liver mitochondria induced by hydrazine when beta-hydroxybutyrate is the substrate. A high level of sulfate in the absence of added phosphate induces a pseudo state three of the mitochondria. Uncoupling is inhibited by rutamycin. Thus sulfate is activated by the mechanism usually utilized by phosphate, and the target for hydrazine is the bond holding electrophilic sulfate. ATP, ADP, PPi, and Mg++ protect against hydrazine, presumably by causing a conformational change of the phosphorylating enzymes which participate in oxidative phosphorylation. Arsenate also could substitute for phosphate in the transitory uncoupling induced by hydrazine. Uncoupling is again inhibited by rutamycin; thus arsenate is also activated by the enzymic mechanism usually utilized by phosphate. Since sulfate is known to enhance the carcinogenicity of certain carcinogens, these results expand the experimental confluence between oxidative phosphorylation and chemical carcinogenesis and also serve to explain at least in part the "toxic" effects of sulfate. Because of the analogous results with arsenate and sulfate, it is suggested that arsenate, like sulfate, may enhance the carcinogenicity of other carcinogens. The data are compatible with epidemiological studies which implicate some role in carcinogenesis for sulfate (often measured as a sulfur dioxide equivalent) and arsenate.


Effects of phenobarbital and methylcholanthrene on hepatic mixed-function-oxidase activities in hamsters. The effects of the inducers phenobarbital (PB) and 3-methylcholanthrene (MC) on hamster liver mixed-function-oxidase activities were studied. Both inducers increased to content of cytochrome P-450 in the microsomes, aminopyrine demethylase activity, and biphenyl 4-hydroxylase activity when given for 8 days. The ability of liver homogenates from treated animals to activate compounds to mutagens was tested using the Salmonella/microsome test. Neither inducer appreciably altered mutagenicity of 2-acetylaminofluorene, benzidine, benzo(a)pyrene, aflatoxin B1, or sterigmatocystin. Mutagenicity of MC was increased when homogenates from MC-treated hamsters were used as a source of activating enzymes, and this mutagenicity could be correlated with increased biphenyl 2-hydroxylase activity.


Chromosome lateral asymmetry: a sensitive assay for screening teratogenic agents. Pregnant albino mice were administered (ip) embryotoxic doses of three individual teratogens: bromodeoxyuridine, hydroxyurea and mitomycin C on day 10 of gestation. Embryos were removed 4 hr later, a cell suspension was prepared and cultured in the presence of colcemid. Metaphase chromosome spreads were subjected to standard G-banding procedures, and the occurrence and frequency of lateral asymmetry (unequal banding of sister chromatids) was monitored. Embryotoxic levels of all three teratogens produced an increase in the number of asymmetries/karotype. For one of these (mitomycin C), the observed increase was dose-dependent.


Mutagenic activities of 1,2,7,8-diepoxyoctane in Chinese hamster lung cells. The mutagenicity of 1,2,7,8-diepoxyoctane (DEO) was investigated using Chinese hamster lung cells. 6-thioguanine resistance and chromosome aberrations were used as markers for mutagenicity testing. DEO was found to be genetically active and to readily from adducts with radiolabeled nucleotides, as demonstrated through thin-layer chromatography in DEO/nucleotide mixtures. Continuous disappearance of cells carrying chromosome aberrations from the cell populations was observed. Based on the expected frequency, cell death can be interpreted as a result of chromosome abberations. The mutagenic specificity of diepoxyoctane is apparently related to the compound's ability to blind with DNA.


Mutagenicity and carcinogenicity of N-methyl-N'-nitro-N-nitrosoguanidine I. Induction of chromosome aberrations and mitotic anomalies in Chinese hamster ovary cells. Cultured chinese hamster ovary (CHO) cells were exposed to different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for either 24 hr or 6 days. For cytological consequences of MNNG exposure, CHO cells were treated for 24 hr and allowed a 24 hr recovery period prior to analysis; for the estimation of cytotoxicity  of MNNG, cells were treated for 6 days followed by a 6 day recovery period. The cytotoxic effect of MNNG based on the colony-forming ability of treated cells showed a semi-logarithmic decrease in the number of colonies formed with an increase in MNNG concentration. The data on the cytological effect of MNNG on CHO cells demonstrate that the chemical causes both structural and numerical chromosomal anomalies and that the incidence of each aberration type is influenced by MNNG concentration. Karyomorphological analysis of CHO cells treated for 24 hr and fixed after four cell cycles showed a varied chromosome constitution ranging from 18 to 54. Chromosomal structural changes arising from breaks and/or exchanges were of chromatid types. Distribution of breaks along the length of the chromosomes and among chromosomes showed that no chromosome segment or chromosome was preferentially susceptible to the clastogenic effect of MNNG. MNNG-induced chromosomal rearrangements, such as ring configurations, exchanges, and dicentrics, exceeded such cytological errors as fragments and pulverizations. In a descending order of magnitude the induced structural rearrangements were ring chromosomes, triradials, quadriradials, and dicentrics.


Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline. Experiments were designed to determine the effects of feeding the methylxanthines caffeine, theobromine, or theophylline to 4- to 6-week-old males rats at a dietary level of 0.5 percent for periods ranging from 14 to 75 weeks. In the first two experiments, Osborne-Mendel rats were fed the test substances alone or in combination with sodium nitrite to test the hypothesis that these amines might nitrosate in vivo to produce toxic nitrosamine compounds. The compounds failed to produce neoplastic or preneoplastic lesions, but a significant positive finding was the occurrence of severe bilateral testicular atrophy with aspermatogenesis or oligospermatogenesis in 85-100 percent of the rats fed caffeine or theobromine. In a third experiment the methylxanthines were fed to Holtzman rats for 19 weeks to determine whether testicular atrophy would be induced in a second strain of rat. The testicular effects were similar to those in Experiments I and II but were more pronounced. Caffeine and theobromine induced testicular injury in nearly all rats. Theophylline induced severe testicular atrophy in 14 percent of the rats, mild to moderate atrophy in 71 percent, and had no effect in 15 percent. The relative testicular toxicity of the methylxanthines was caffeine, most potent; theobromine, slightly less potent; and theophylline, considerably less potent. Somewhat variable atrophic changes of the accessory sexual organs (epididymis, prostate, and seminal vesicles) accompanied the testicular changes. Cytogenetic analysis of testes from caffeine- or theophylline-treated rats revealed a significantly reduced number of mitotic cells in the caffeine-treated group. Plasma testosterone concentrations were significantly elevated in the theobromine group and somewhat elevated in the caffeine-treated group; this correlated morphologically with an apparent hyperplasia of interstitial cells in severely atrophied testes in these groups. Plasma cholesterol concentrations were significantly increased in the caffeine and theobromine groups. Possible sites and mechanisms of action of the methylxanthines in the induction of testicular atrophy and impaired spermatogenesis are discussed.


Aflatoxin B1 and aflatoxicol metabolism in rainbow trout (Salmo gairdneri) and the effects of dietary cyclopropene. Aflatoxin M1 was identified as a minor metabolite formed by the in vitro incubation of aflatoxin B1 with the postmitochondrial fraction or microsomes from rainbow trout (Salmo gairdneri) liver. Fresh, whole trout liver converted perfused aflatoxin B1 to aflatoxicol and aflatoxin M1, and converted perfused aflatoxicol to aflatoxin B1 and aflatoxin M1. AFB1 reductive activity was found in the 105,000 xg supernatant, while activity converting AFL to AFB1 was distributed about equally in the 105,000 xg supernatant and in the microsomal pellet. Transformation of AFL to AFB1 was not inhibited by CO, but formation of AFM1 was completely blocked. Cyclopropene fatty acids (CPFA)-fed fish produced only one-half to one-third as much AFL from AFB1 as controls, and they produced no detectable AFM1. Most of the unreacted AFB1 was recovered by extraction of the incubation medium by organic solvent whereas, in controls, much of it remained bound to the protein. There was no difference in conversion of AFL to AFB1 when results were expressed in terms of postmitochondrial protein levels. CPFA-fed fish had lower microsomal protein and cytochrome P-450 levels and NADPH-cytochrome c reductase and aldrin epoxidation activities than did controls.


Stimulation of DNA synthesis in lungs of hamsters tolerant to nitrogen dioxide. Nitrogen idoxide (NO2) is both edematogenic and cytotoxic to the lung. Preexposure to NO2 protects against mortality from formation of excessive pulmonary edema (tolerance) and, depending on the preexposure schedule, may or may not protect against the cytotoxic effects of NO2 in the lung. Measurement of DNA synthesis in hamster lung was used to study the question of whether the more subtle cytological injury induced by NO2 is mediated by a system which also exhibits tolerance. It was found that when hamsters are preexposured daily to 10 ppm NO2, they develop tolerance against normally lethal concentrations of NO2; are protected against further cytological injury from 10 ppmNO2; but are not protected from the cytotoxic effects of NO2 greater than 10 ppm. Animals exposed weekly to 10 ppm NO2 are not protected from further cytotological injury induced byweekly exposures to 10 ppm NO2, but do develop tolerance against lethal concentrations of NO2. Thus the data indicate that induction of tolerance to NO2 does not necessarily protect the cell populations of the lung from the cytotoxic effects of NO2.


A rapid bioassay system for lead using young Japanese quail. A rapid bioassay of lead was established in young japanese quail. Each group of 10 day-old birds received deionized water and a purified diet ad libitum for 2 wk. The diet contained 0.2 microgram lead/g. Lead acetate was added to give 14.8, 34.4, 51.2, 74.4, 234, 563, or 1223 microgram total lead/g by analysis. The duodenum, kidneys, liver and tibias were assayed for lead. Consumption of a diet containing either 563 or 1223 ppm lead caused a decrease (P less than or equal to 0.05) in body weight after 1 wk and an increase in free erythrocyte protoporphyrin after 2wk. Inhibition of red blood cell delta-aminolevulinic acid dehydratase (RBC-ALAD) activity occurred in birds consuming as little as 14.8 ppm lead. Packed cell volumes and hemoglobin concentrations were not affected by the dietary treatments. Lead concentrations in tissues from birds fed the lowest level of added lead were greater than those found in the corresponding tissues of control birds. The concentration of lead in the tibia showed the most distinguishable group means and the most nearly linear response; the highest slope was between 14.8 and 110 ppm dietary lead, using log-log transformations. The rapid bioassay is suitable for investigating high lead foods.


Effect of cadmium on salt hypertension in rats. The suggestion that cadmium-induced hypertension in rats might be due to renal sodium retention, known to result from Cd treatment, was examined. Young female rats were given a regimen of intraperitoneal cadmium treatments reported to cause hypertension reliably within a month. They were sensitized to the development of salt hypertension by removal of one kidney and then given 1 percent saline solution to drink. Over a five-week period, experimental animals consistently drank more saline than controls, despite which fewer of them became hypertensive, with the result that the average systolic pressure of controls finally reached the hypertensive range, whereas the experimental group remained normotensive. Cadmium treatment had no detectable effect on growth, the hemogram, serum Na and K, or the weight of liver, kidney, heart, spleen, thymus, or adrenal glands. There was thus no evidence that cadmium caused any adverse constitutional or hemodynamic effects, but it appeared to retard the development of salt hypertension. The results do not support the suggestion that the hypertensive effects of cadmium are modulated by sodium-retaining influences on the kidney.


Safety evaluation of toothpaste containing chloroform. I. Long-term studies in mice. In three experiments, chloroform was administered to mice by gavage in a toothpaste base or in arachis oil, in doses up to 60 mg/kg/d on 6 days/wk for 8 wks. Control groups were left untreated or given vehicle only. In general, there were more survivors in chloroform-treated groups than in the controls. In the case of the males of three strains (C57BL, CBA and CF/1), treatment was associated with no adverse affect on the incidence of any type of neoplasm or any other parameter. In the males but not the females of a fourth strain (ICI) and in doses of 60 mg/kg/d but not of 17 mg/kg/d, exposure to chloroform in toothpaste base as a vehicle was associated with increased incidence of epithelial tumours of the kidney. A more pronounced effect of the same kind was seen in mice given 60 mg CHCl3/kg/d in an archis oil vehicle. This treatment was also associated with a higher incidence and severity of non-neoplastic renal disease. The mechanisms underlying the peculiar strain- and sex-specific susceptibility of ICI male mice to develop renal tumours when exposed to chloroform remain obcure; spontaneous renal tumours were also seen in vehicle control mice and possible ways in which this tendency may be enhanced by chloroform treatment are discussed. At the dose levels tested, namely 113 and 400 times average human exposure levels from the use of toothpaste (with 3.5 percent chloroform content), no adverse affect was seen in the liver and there was no increased incidence of liver tumours even in the higher liver tumour susceptible CBA strain. At the 17 mg CHCl3/kg/d level, equivalent to 113 times average human exposure from toothpaste use, no excess of renal tumours was seen even in males of the peculiarly susceptible ICI strain.


Safety evaluation of toothpaste containing chloroform. II. Long term studies in rats. The results of a preliminary rangefinding 13-wk oral toxicity study and of two longer term studies on chloroform in toothpaste base are reported. Significant changes in serum enzymes and certain haemotological parameters were seen at the higher dose-levels in the rangefinding study. Intercurrent disease made it necessary to terminate the first long-term experiment prematurely after 1 yr. No evidence of serious toxicity was recorded. In the second long-term experiment, groups of 50 caesarian-derived SPF Sprague-Dawley rats of each sex received either the equivalent of 60 mg CHCl3/kg/d in toothpaste base or the vehicle only, by gavage on 6 d/wk for 80 wk and were then observed for up to a further 15 wk. Chloroform-treated rats of both sexes survived better than the controls, though both groups had a high incidence of non-neoplastic respiratory and renal disease. Female rats gave a consistent finding of decrease in plasma cholinesterase, shown to be related to activity against butyrylcholine but not acetyl-beta-methylcholine. Tumours of various sites were seen in 39 percent of chloroform-treated rats of both sexes examined histologically, compared with 38 percent of vehicle controls. There were no treatment-related effects on the incidence of liver or kidney tumours. Histologically-malignant mammary tumours were reported in more treated than control rats, but the difference in incidence was not statistically significant.


Safety evaluation of toothpaste containing chloroform. III. Long-term study in beagle dogs. Beagle dogs were given chloroform in a toothpaste base orally in gelatin capsules on 6 d/wk for 7 1/2 yr, followed by a 20-24 wk recovery period. Groups of 16 males and females received 0.5 ml/kg/d of the vehicle (toothpaste without chloroform) and 8 dogs of each sex remained untreated. Treated groups comprised 8  dogs of each sex remained untreated. Treated groups comprised 8 dogs of each sex, receiving doses equivalent to 15 and 30 mg CHCl3/kg/d in the toothpaste vehicle; another group of the same size received an alternative non-chloroform toothpaste (0.5 ml/kg/d). Eleven of the 96 dogs died during the study, only two of these being in the CHCl3-treated groups. The only significant toxic response during treatment was a moderate rise in serum enzyme levels (e.g. SGPT), reaching a peak in the sixth year of the study and probably corresponding to minimal liver damage. Few Palpable growths were noted while the dogs were alive. "Fatty cysts" were seen in the liver of several dogs at post mortem possibly associated with the chloroform treatment but the distribution of a nodular change in the liver was not obviously dose related. A small number of macroscopic and microscopic neoplasms were seen; one dog in each chloroform-treated group had a malignant tumour but there were no tumours in the liver or kidney of any dog. Overall, exposure to chloroform in a toothpaste base was not associated with any effect on the incidence of any kind of neoplasm. From this and related studies in mice and rats, it is concluded that repeated exposure to chloroform (3.5 percent) in toothpaste is unlikely to result in any hazard to human health.


Pharmacokinetics of triclosan in rat after intravenous and intravaginal administration. The pharmacokinetics of triclosan was studied in sexually mature virgin Wistar rats. 14C-triclosan was injected either via the femoral vein, (iv, 5 mg/kg in polyethylene glycol-400) or into the vaginal orifice (ivg, 5 mg/kg in corn oil). Radioactivity was determined by liquid scintillation spectrophotometry. After iv administration, the dissapearance of 14C from the blood followed the kinetics of a two-compartment open-system model. The apparent volume of distribution was 42 percent of the body weight, which is more than the extracellular water, suggesting a rapid transfer of this antimicrobial agent from plasma to tissues. The blood half-life of 14C during the beta-phase was 8.8 +/- 0.6 hr and the blood clearance rate was 77.5 +/- 11.3 ml/kg/hr. After ivg administration of 14C-triclosan, the radioactivity was detected in tail blood at 15 min, peaked between 2 to 4 hr, and declined rapidly to 6 hr more slowly thereafter. About 26 percent of the administered dose remained in the vagina after 4 hr and 12 percent after 24 hr. Tissue concentrations of 14C were highest in the plasma, kidney, and liver after ivg application, but extremely low in the brain, fat, and skeletal muscle. The percentages of the dose excreted in 24 hr in the feces and urine were 18 and 9 after iv administration, compared to 26 and 14 after the ivg route, respectively. The results show that triclosan is rapidly absorbed through the vaginal mucosa of the rat.


Association between chloroform levels in finished drinking water supplies and various site-specific cancer mortality rates. This paper discusses some of the statistical and biological problems that are likely to be encountered when an indirect or ecological approach is used to assess the possible public health impact of general population exposures to environmental agents. For purposes of illustration, the potential association between various site-specific cancer mortality rates and chloroform levels in public drinking water supplies was considered. The analyses that were performed demonstrated that, for the data sets under consideration, there were some definite associations between chloroform levels and cancer mortality for specific sites such as the rectum-intestine and bladder. However, the marked extent to which these results were dependent on (1) the weighting scheme adopted in the analysis, (2) the presumed appropriateness of the data, and (3) the characteristics of the statistical model was also clearly illustrated. Because of these dependencies the quantitative, causal interpretation of results generated from an indirect study would appear to be a very tenuous and questionable practice in most instances.


Problems of identification in the clinical laboratory, state of the art and other considerations. In recent years, there have been no new commercial developments in identification methods for the clinical chemical laboratory. We are still faced, however, with the problem of ensuring accurate identification. By using a model, the importance of reliable identification can be shown mathematically. The complete identification of a sample is based on a five point identification statement. As a rule, appropriate measures are taken to abridge this identification process, depending on the local situation. The terminology of identification processes is defined and the presently available techniques are discussed.


Thyroid tumors in rats from tetramethylthiourea. Tetramethylthiourea (TMTU) was added to the diet of male and female ChR-CD rats for up to 2 years at levels of 0, 30 and 300 ppm. Fifty rats of each sex were used at each dietary level. High-level males and females and low-level males had a lower body weight and consumed less diet than did the controls. A slight anemia was found in the high-level males and females. Polyuria of a low osmolality was found in high level males and females. Serum thyroxine was lower in high-level males and females than in controls. TMTU-related gross and histologic changes were detected only in the thyroids of high-level males and females. After 3 months on test, the thyroids were enlarged and dark on gross examination. Histologically, there was an increase in follicle lumen size, loss of colloid staining, hypertrophy and hyperplasia of follicular cells, together with hyperemia. These early lesions were diffuse in distribution. Eight (28 percent) of 29 female high level rats, 18 to 24 months on test, developed follicular cell carcinomas with no such tumors in 26 comparable controls (p less than 0.005, Fisher's Exact Test, one tail). Although no metastases were found, capsular and vascular invasion by tumor cells was seen. TMTU was considered to be carcinogenic for the female rat under the conditions of this test.


[Determination of Li, Na, K, Mg and Ca with a mechanised flame photometric micro-method. Mechanised micro-method ("injection method") of flame photometry (atomic absorption--atomic emission) for the determination of serum electrolytes and trace elements (Fe, Cu, Zn); Part I. (author's transl)]. By introduction of the analysis solution in measured quantities in atomic absorption and atomic emission spectrometry, the quantity sensitivity of these methods can be increased by an order of magnitude, while the concentration sensitivity remains unchanged. The required volume of sample (serum) is thereby considerably reduced. Using this method, the serum electrolytes and certain trace elements can be determined simply and quickly in only a few microlitres of serum. The automation of this micro-sample application ("injection method") largely abolishes individual errors, and markedly shortens the time for the analysis of large series of samples. The first part of this paper describes the determination of serum electrolytes and lithium, using only 5--20 microliters of serum.


A critical appraisal of a further three new commercial digoxin radioimmunoassay kits with reference to cross-reacting substances. A further 3 digoxin radioimmunoassay (RIA) kits have been evaluated for performance and cross-reaction with digitoxin, spironolactone, canrenone and furosemide (Lasix-Hoechst). Effects of serum protein concentrations have also been tested. The kits tested were from the following manufacturers: A) Diagnostic Products Corporation Digoxin RIA Kit. B) Byk-Mallinckrodt SPAC Digoxin Kit. C) Boehringer-Mannheim Digoxin RIA Kit. All kits used a 125I-labelled tracer. Kit A used a conventional liquid phase system using double-antibody separation for bound and free drug, Kits B and C used a solid-phase antibody coated tube method. All kits showed a lower cross-reaction to digitoxin than quoted by the manufacturer. Cross-reaction to spironolactone (Aldactone--Boehringer-Mannheim) was less than 1.50 nmol/l at a serum concentration of 125 mg/l Aldactone in all 3 kits. The cross-reaction to canrenone was somewhat higher, 5.2 nmol/l "digoxin" being measured in one kit at a serum canrenone concentration of 125 mg/l. There was no cross-reaction with furosemide in any kit, even at a serum concentration of 5 g/l. The coated-tube assays were affected by serum albumin and globulin concentration changes, one kit showing a difference of over 50% binding in the range 1--20% albumin. The double-antibody kit did not show dependence on the concentration of these proteins. All kits measured digoxin with good reproducibility in the range 0.40--10.0 nmol/l.


Inhibition of creatine kinase activity and alterations in electrophoretic mobility by palladium ions. The toxicological consequences of increased levels of palladium in the environment have not yet been assessed. In this paper, the effect of palladium ions (Pd) on purified rabbit  muscle creatine kinase (CPK-MM) and on human serum CPK-MM was examined. When rabbit muscle CPK-MM was treated with Pd, a concentration-dependent inhibition of enzyme activity with a calculated Ki of 0.16 mumol, associated with a marked increase in a electrophoretic mobility of the enzyme toward the anode, was observed. Pd exerted the same effect of human serum CPK-MM, but to a lesser extent. Analysis of binding of Pd to CPK-MM by a colorimetric competitive-binding technique, using chlorpromazine-chromophore, as well as by a dialyzing technique, indicated that the cation may form an extremely strong complex with essential SH groups of the enzyme.


[Detection of the new analgetic Tramadol (Tramal) (author's transl)]. Analytical data (TLC, GLC, UV, IR, MS) of the new analgetic, Tramadol are described. Extraction of the material from biological samples and preliminary results on its biotransformation are also reported.


Water pollution and diseases in fish (an epizootiologic survey). Three watersheds, varying from highly polluted or moderately polluted to essentially pollution-free, were surveyed to determine the frequency of fish disease. Over a five year period, it was found that a relationship existed between the level of pollution and frequency of disease. The occurrence rates of microbial and oncogenic diseases increased similarly in relation to increases in pollution in the waters. Since the water systems studied provide recreational opportunities for man, it is suggested that catching and subsequent ingesting of diseased fish from these waters present a health hazard.


[A simple gas chromatographic method for the determination of barbiturates in serum (author's transl)]. A simple gas chromatographic method for the determination of commercially available barbiturates used as hypnotics is presented. Saturated ammonium sulfate is added to the serum sample. The mixture is extracted three times with chloroform. The organic layer is dried over sodium sulfate and evaporated. The residue is dissolved in ethyl acetate/acetic acid (100 ml + 1 ml) and an aliquot is injected into the gas chromatograph. The precision in the series is between 3.0 and 7.2%; the recovery--with the exception of propallylonal--between 91 and 108%; the detection limit from 1.7 to 6.9 mumol/l. The specificity of the method was checked by comparing 1) the results obtained before and after additional purification of the extract by thin-layer chromatography, and 2) the retention times of about 100 drugs in the gas chromatographic systems that are used.


2,3-Dihydroxybutane: an unusual compound found in the gaschromatographic analysis of volatile compounds of urine. 2,3-Dihydroxybutane, a compound not observed in normal urines, was identified in the urine of two patients by combined gas chromatography-mass spectrometry. It is suggested, that this 2,3-dihydroxybutane is derived from pyruvate by bacterial metabolism.


Rift Valley fever virus: some ultrastructural observations on material from the outbreak in Egypt 1977. Rift Valley fever virus isolates from the 1977 outbreak in Egypt were studied at an ultrastructural level. The particles measured 90 to 110 nm in diam. using negative staining and sectioning techniques, with a core component of 80 to 85 nm. The surface of the virions was calculated to be covered by approx. 160 sub-units. The particles were found in smooth endoplasmic reticular systems, which were made up of either multi-tubular complexes, or of a single large vacuole. The majority of these membrane systems were found to be unassociated with Golgi apparatus. Inclusion bodies were found within the host cell nuclei (made up of rods and fine granules) and in the cytoplasm (aggregates of fine or coarse granules). The possible relationship of these structures to virus replication is discussed.


Chemical characterization of Rauscher leukaemia virus proteins. The proteins of Rauscher murine leukaemia virus (R-MuLV) were characterized by amino acid analyses and by determination of their mol. wt. by gel filtration on cross-linked Sepharose 6B in 6M-guanidine hydrochloride (GuHCl). Molecular weights of 56,000, 29,000, 15,000, 10,500 and 7,600 were found for gp70, p30, p15, p12 and p10 respectively. The amino acid compositions of these proteins and of p12E have been determined. The amino acid compositions of the p10 polypeptides of Rauscher-MuLV and Moloney-MuLV are very similar as are those of the p30 polypeptides, whereas the amino acid compositions of the p12 polypeptides differ considerably. P12E contains the highest percentage of hydrophobic amino acid residues. Among the gag-gene coded proteins, p15 contains the highest percentage of hydrophobic amino acid residues while p12 and p10 contain the lowest.


Sex differences in the perception of autokinetic movement of an afterimage. The effects of stimulus color and gender upon the perception of an afterimage were examined. The Ss were 32 male and 32 female college undergraduate volunteers. Eight Ss of each gender viewed a pinpoint flash of light through one of four filters: blue-green (Wratten 44A), red (Wratten 92), yellow (Wratten 9), or a neutral (Wratten 96) filter. Each S was given three trials, and on each trial, the duration of the afterimage was recorded, along with changes of direction, and changes in perceived color. Males reported significantly (p less than .05) more autokinetic movement of the afterimage. The color of the stimulus affected afterimage duration differentially for the two genders (p less than .05), and there was also a significant interaction (p less than .02) of gender with filter color for the total number of color changes reported. Thus, it is likely that both outflow monitoring and error signal variables in the autokinetic effect may be affected by gender, and the two sexes may also have different retinal and/or central processing of visual information.


Investigation of brachial plexus traction lesions by peripheral and spinal somatosensory evoked potentials. Peripheral, spinal and cortical somatosensory evoked potentials were recorded in 26 patients with unilateral traction injuries of the brachial plexus ganglia. Of 10 cases explored surgically the recordings correctly anticipated the major site of the lesion in eight.


Late sequelae of paralytic poliomyelitis: a clinical and electromyographic study. A prospective study was carried out on 24 volunteers who had suffered from paralytic poliomyelitis up to 51 years earlier. A quantitative EMG was carried out in each subject. Grossly raised mean amplitudes of the interference patterns were found in many strong muscles as well as in weak muscles. Such muscles frequently showed "contraction fasciculation", a manifestation of loss of normal small motor units. In many subjects the clinical and EMG evidence of chronic partial denervation were more widespread than the subjects had realised. It is suggested that if, with advancing age, minor damage occurs to the peripheral nervous system and the complement of motor neurones is already depleted by poliomyelitis, there will be an exaggerated response with increase in the lower motor neurone signs.


Functional consequences of the transcallosal removal of intraventricular tumours. Colloid cysts and other benign tumours of the third and lateral ventricles may be exposed through a small incision in the body of the corpus callosum. This approach is practicable even when ventricular dilatation is slight, and is theoretically less likely to cause epilepsy than the more usual transcortical approach. Disturbances of memory have been noted soon after such operations, but do not cause serious long-term disability. Three patients who underwent transcallosal removal of cysts or tumours some years earlier have been tested by procedures designed to demonstrate interhemispheric transfer of information: they were all found to have defects in transfer of tactile data, but not of information obtained visually. They were not aware of this inability, and do not appear to be inconvenienced by it. The transcallosal route is convenient. The operation sacrifices a functionally significant part of the corpus callosum, but the neurological sequelae have seemed acceptable. However, especially in the elderly, stereoventriculoscopic aspiration may be considered as the initial method of treatment.


Long-term treatment of Parkinson's disease with bromocriptine. BRomocriptine (15-75 mg per day) alone or with L-dopa was studied during five to 29 months on 44 patients with Parkinson's disease. Used as sole therapeutic agent, it was found excellent in 12 patients who had never received regular L-dopa treatment either because it was never attempted or because of intolerance from the outset. Its anti-Parkinsonism activity was comparable with L-dopa. The gain was stable in the long term until this report. The side effects of L-dopa were not seen after bromocriptine. In cases where L-dopa had ceased to be active, bromocriptine produced a further improvement if mental deterioration was not associated. In very advanced forms of Parkinson's disease with associated dementia, bromocriptine did not produce durable results. Bromocriptine did not improve the "on-off" effects but reduced a number of the side effects of L-dopa, in particular cardiac, painful contractions, and dyskinesia without "on-off" effects.


Vocal cord paralysis in the Shy-Drager syndrome. Eight out of 12 unselected patients with Shy-Drager syndrome were found to have severe bilateral paresis of vocal cord abduction by fibre-optic laryngoscopy. This commonly presented as increased snoring followed by episodes of inspiratory and expiratory stridor and sometimes by sleep apnoea. Respiratory failure eventually developed in four cases and was reversed by tracheostomy. In another patient tracheostomy relieved severe attacks of sleep apnoea. This complication was not necessarily associated with advanced disease, and it should be considered in all patients with Shy-Drager syndrome as appropriate treatment can lead to a useful extension of life.


Neonatal polycystic encephalomalacia: four new cases and review of the literature. Four patients with pathologically documented polycystic cavitation of the brain had an acute illness characterised by stupor, seizures, CSF erythrocytic and monocytic pleocytosis, increased CSF protein, and diminished CSF glucose. The acute phase was followed by chronic decerebation, disappearance of the CSF abnormalities, and radiological evidence of polycystic cavitation of the brain. In one patient Herpes simplex was isolated from a cutaneous vesicle. The CSF abnormalities in the disorder have received scant attention, and have not previously been correlated with the acute and chronic stages. Clearly some cases are associated with Herpes simplex virus. The clinical profile should now be sufficiently distinctive to permit future identification of the aetiology in more neonates.


Characteristics of the F response: a single motor unit study. Trains of 100 to 200 stimuli result in F discharges from less than one half of motor units of hand muscles. The maximum observed F discharge frequency was 10%. There was no relation between the surface voltage of motor unit potentials and the frequency of F discharge. The motor unit potentials of larger surface voltage were recruited at higher stimulus intensity levels, usually supramaximal for the antidromic sensory nerve action potential. No correlation was observed between F latency and the surface voltage of the motor unit potentials. In only one pathological example was a clear interaction observed between the frequency of F discharge in motor unit potentials and the recruitment of other single motor unit potentials by increments in the stimulus intensity. The observations suggested that caution should be exercised before the F discharge is accepted as a method for measuring proximal conduction times in human motor nerves.


Effects of 4-aminopyridine in myasthenia gravis. A new drug, 4-aminopyridine, was prepared for use in humans and tested by repeated injections in six patients with myasthenia gravis. The drug caused improvement of muscle strength and neuromuscular transmission as demonstrated by clinical observations and repetitive electrical nerve stimulation. The drug was effective in cases without any other treatment as well as in cases undergoing treatment with anticholinesterases. It is concluded that 4-aminopyridine may be of value as a supplementary drug in the treatment of myasthenia gravis.


Myelopathy in Marfan's syndrome.

Myelopathy in Marfan's syndrome. A patient with Marfan's syndrome and a myelopathy is reported, and the association of multiple spinal arachnoid cysts noted. It is proposed that the basic connective tissue defect in Marfan's syndrome may predispose to the formation of arachnoid diverticuli and that in this case spinal cord damage was the sequel.


HLA antigens in chronic relapsing idiopathic inflammatory polyneuropathy. Observations are reported on 14 patients with a clinical diagnosis of recurrent or chronic relapsing idiopathic inflammatory polyneuropathy of Guillain-Barré type. The results suggest the possibility of a disease susceptibility gene for this disorder associated with the HLA-A1, -B8, -DRw3, and -Dw3 haplotype.


Pseudoclaudication syndrome caused by a tumour of the cauda equina. A typical case of pseudoclaudication syndrome (neurogenic intermittent claudication), where the cause of the lumbar spinal canal narrowing was an intraspinal neoplasm, is reported. A neoplasm as the cause of this syndrome seems to be very rare, possibly because of the progressive nature of the space-occupying lesion and hence the rapid development of other predominant symptoms.


Regeneration of sutured human peripheral nerves: an electrophysiological study. Electrophysiological and clinical assessment of recovery of function was undertaken on 34 median and 33 ulnar nerve which had been resutured after complete section three and a half months to 24 years previously. An evaluation of different methods of repair was attempted. Our results suggested that re-exploration of the site of suture is indicated in the absence of voluntary activity on needle EMG by seven months (12 months for grafts), of an electrically evoked muscle action potential, measurable distal motor latency, or motor nerve conduction velocity by 10 months (14 months for grafts), or of clinically detectable voluntary muscle movement by 10 months after suture. By present techniques of repair useful prognostic information cannot be obtained by a consideration of sensory parameters either clinical or electrophysiological.


Proprioceptive fields of crayfish claw motor neurons. 1. Action potentials of crayfish claw motor neurons were recorded during both imposed constant-velocity displacements and imposed alternating sequences of opening and closing step movements of the dactyl. 2. Peristimulus time (PST) histograms show that the firing probabilities of two neurons, the opener inhibitor (OI) and the slow closer excitor (CE) consistently increased during opening ramp movements and declined during closing ramp movements. Hyperpolarizing synaptic potentials were observed in both cells during closing movements. 3. The proprioceptive field organizations of OI and CE were analyzed with response planes and contour planes. Each PST histogram in a plane displays the firing probability of the neuron as a function of time following step displacements at a given position. A relatively uniform early primary response followed each successive opening step. The probability of occurrence of later activity, when present, usually became more pronounced as the joint angle increased. Often both cells were silent during closing steps; when the cells were active, their firing probabilities were highest at the more open joint angles. 4. When both OI and CE were active, their spike trains were usually temporally correlated. 5. The other claw efferents did not respond to imposed movements in a consistent manner. When CE was active it was most likely to respond to closing movements near the closed position. 6. It is concluded that OI and CE are strongly and similarly influenced by proprioceptive reflexes. The responses of the two cells to imposed dactyl movements change as a function of joint angle, time after movement, and direction of movement.


Interactions among an ensemble of chordotonal organ receptors and motor neurons of the crayfish claw. 1. Action potentials of crayfish propodite-dactyl (PD) chordotonal organ receptors and two claw motor neurons, the opener inhibitor (OI) and slow closer excitor CE) were simultaneously monitored during imposed step and ramp movements of the dactyl or while the dactyl was held at various positions. 2. The activities of the cells during imposed displacements were analyzed using peristimulus time histograms and response and contour planes. The proprioceptive fields (PFs) of individual receptors resemble components of the more complex motor neuron PFs. Some receptors are briefly active after each successive opening step, while others do not respond to steps near the closed position but respond as the joint angle increases, becoming active when the claw is held open. Another type of receptor responds to closing movements. 3. Interactions among the various types of receptors and the two motor neurons were detected and analyzed by various statistical methods and intracellular recording techniques. The results indicate that receptors activated during opening movements and when the dactyl is held at open positions excite OI and CE via divergent functional connections. The efficacies of the connections made by a receptor may differ. Receptors activated by closing movements produce hyperpolarizing synaptic potentials in both efferents, possible directly or via interneurons. 4. It is concluded that several types of chordotonal organ receptors form an ensemble of parallel input channels, which modulates the activities of OI and CE and contributes to the generation of the spatial-temporal nonuniformities of their proprioceptive reflex responses.


Adaptation in catfish retina.

Adaptation in catfish retina. 1. We define absolute sensitivity as (voltage/illuminance) and incremental sensitivity as the peak-to-peak amplitude of the first-order (Wiener) kernels. 2. Incremental sensitivity of the horizontal cells is the local slopes of the Michaelis-Menten equation and that of more proximal neurons is the Fechner slope. In a log-log plot, the former has a slope of -2, whereas the latter a slope of -1, as predicted by Williams and Gale (39). 3. During a moderate to strong steady illumination, absolute sensitivity decreases but incremental sensitivity increases. The reverse occurs during dark adaptation. 4. The presence of a steady illumination did not prevent signal transmission from horizontal to ganglion cells. 5. From these results we conclude that: adaptation in the catfish retina includes two components: a) a lateral shift of the voltage-intensity curve along the intensity axis, and b) changes in the time course of light-evoked response. We argue that the latter phenomenon is related to the presumed horizontal cell-to-receptor cell negative feedback.


Identifiable neurons controlling penile eversion in the leech. 1. This paper describes the neuroanatomy and electrophysiology of motor neurons causing penile eversion in the leech. 2. The male organ is innervated by ganglia 5 and 6 of the 34 ganglia in the leech brain through special sex nerves deriving from anterior roots. These sex ganglia have at least 200 more neurons than the other midbody ganglia. Many of the extra neurons are involved in reproductive behavior. 3. Two pairs of motor neurons on the ventral side of ganglion 6, named rostral and lateral neurons, are the only ones that elicit full penile eversion. Evidence that the lateral and rostral neurons are, in fact, motor neurons comes from HRP and electrophysiological studies. HRP injections reveal that each neuron's single primary axon grows into the sex nerve. Electrophysiological evidence is twofold: a) action potentials of lateral and rostral cells can still contract the genitalia after the neurons are deafferented from chemical synaptic input in the ganglion by high Mg2+, b) their action potentials are followed by junction potentials in male organ muscle fibers.


Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis. 1. Starting with published data derived mainly from hippocampal slice preparations, we have used computer-modeling techniques to study hippocampal pyramidal cells (HPCs). 2. The dendrites of the HPC apparently have a short electrotonic length. Calcium spikes are apparently generated by a voltage-dependent mechanism whose kinetics are slow in comparison with those generating sodium spikes of the soma. Inward calcium currents are assumed to trigger a long-lasting potassium conductance. This slow calcium-potassium system, which in our model is located predominantly on the dendrites, provides a heuristic model to describe the mechanism for a) the after-depolarization following an HPC soma (sodium) spike, b) the long afterhyperpolarization following repetitive firing, c) bursts of spikes that sometimes occur after orthodromic or antidromic stimulation, and d) the buildup of the "depolarizing shift" during the strong synaptic input presumed to occur during seizures. 3. Fast prepotentials or d-spikes are shown to arise most probably from dendritic "hot spots" of sodium-regenerative membrane. The limited amplitude and short duration of these prepotentials imply that the hot spots are located on small dendrites. 4. Dendritic electroresponsiveness, first postulated for the HPC by Spencer and Kandel (52), is analyzed quantitatively here and is shown to provide rich integrative possibilities for this cell. Our model suggests that, for these nerve cells, alterations in specific membrane properties, particularly calcium electroresponsiveness, can lead to bursting behavior that resembles epileptogenic neuronal responses.