A factor-analytic study of criteria for evaluating student clinicians in speech pathology. This study was designed to determine the most significant criteria used in university training programs to evaluate the therapeutic effectiveness of student clinicians enrolled in clinical practicum. A total of 152 supervisors in 53 ASHA accredited training programs used 40 criteria to evaluate 207 clinicians engaged in speech and language therapy. Factor analysis yielded two distinct dimensions, Technical Skills and Interpersonal Relationship Factors, and indicated that 18 variables contributed most significantly to the evaluative process. Student clinicians were consistently rated higher on variables related to the interpersonal dimension than on those related to technical skills. The identification and structure of the 18 variables suggests that both technical and interpersonal skills are widely regarded as essential to therapeutic effectiveness. The results provide insight into the nature of clinical evaluation and behavior and suggest a restructuring of criteria for evaluating the process of therapeutic treatment.


Comparative study of three routes of administration of sisomicin. A comparative study was performed using three routes of administration of sisomicin (1 mg/kg as single dose): intramuscular injection, intravenous rapid injection, and 1-hour infusion. Intravenous administration resulted in higher blood levels immediately after the injections than by the intramuscular route; however, later, the intramuscular injection resulted in optimal blood levels. High levels of sisomicin which were bactericidal for most Gram-negative bacilli were found in the urine of the treated patients. The antimicrobial activity of the serum obtained 1 hour after administration of sisomicin, as determined against 20 strains of Gram-negative microorganisms isolated from blood cultures, was identical with all three routes of administration of sisomicin.


Verbal behavior of interviewees: the effects of several situational variables on verbal productivity, disfluency, and lexical diversity. Interviewer status (high vs. low) and anticipated evaluation (positive vs. negative) were manipulated orthogonally to test competing predictions derived from Hull-Spence and Mahl-Osgoood drive theory hypotheses. The effects of question specificity, interview topic, and interview segment were examined concomitantly. Verbal behavior measures were total words per interviewee response, mean segmental TTR (25), partial mean segmental TTR (25), and ratio of disfluency per response. Results for disfluency tended to support the Mahl-Osgood hypothesis. Lexical diversity results offered weak support for the Hull-Spence hypothesis. Results for verbal productivity failed to support either of the hypotheses and were interpreted as possibly supporting the Duffy-Malmo inverted U hypothesis. Generally, the results suggested that the unitary construct "drive" may be inadequate for explaining the effects of specific situational variables upon verbal behavior.


Self-disclosure in parents of stuttering children. A review of the literature suggested a possible relationship between low self-disclosure or avoidance of the self in parents and stuttering in the child within the same family. The present research was designed to test whether there are any differences in self-disclosure between parents of stuttering children and parents of nonstuttering children. The Self-Disclosure Questionnaire, devised by Jourard, was administered to 64 mothers and 64 fathers, half of whom comprised the control groups. The results obtained by analyses of variance indicated that parents of stuttering children do not differ from parents of nonstuttering children in their actual self-disclosure. However, findings as to why disclosure did not occur on certain items indicated that, although the parents of stuttering children do not differ in self-disclosure, they may differ in declining to disclose information when asked for it.


Renal effects of guanabenz: a new antihypertensive. In order to determine the effects of guanabenz upon renal function, clearance studies were performed on hypertensive volunteers during sustained steady-state water diuresis. The data reveal an acute fall in renal hemodynamics and a marked reduction in sodium excretion during the 3rd and 4th hour after administration. Tha antinatriuresis was due to decreased filtration and enhanced distal nephron reabsorption of sodium, principally in association with secretion of potassium. Chronic administration of guanabenz for one week produced a sustained reduction in blood pressure, but there was no change in either body weight or 24-hour urinary sodium excretion. Repeat clearance studies revealed no change with either renal hemodynamics or sodium clearance. The data suggest that the acute antinatriuresis is a transient hemodynamic event and chronic therapy with guanabenz will not be complicated by sodium retention, a feature characteristic of other antihypertensive agents.


Recall of sentence meaning in aphasic and nonaphasic adults. The hypothesis that memory for spoken sentences is facilitated by memory for sentence meaning was tested with 16 aphasic and 8 nonaphasic adults. Subjects were asked to make judgments of same or different on pairs of active and passive sentences separated in time. Sentence pairs were either identical in all respects or identical in just grammatical structure, subject-verb-object word order, or meaning. Nonaphasic subjects had higher sentence recognition scores, and larger percentages of meaning preserving responses than aphasic subjects. Aphasic subjects with the highest recognition scores made more meaning preserving responses than aphasic subjects with the lowest recognition scores. The results suggested that memory for spoken sentences is facilitated more by memory for sentence meaning than memory for structure of wording.


Confusions in recognizing phonemes spoken by esophageal speakers: II. Vowels and diphthongs. A methodology was developed to determine the patterns of phonemic errors that listeners would make in receiving the vowels and dipthongs of monosyllables spoken by esophageal speakers. Analyses of the features preserved in the errors were performed. The identified phonemic error patterns and the features found to be poorly preserved in the errors were used to structure multiple-choice intelligibility practice materials for esophageal speakers.


Analysis of responses to the Berry-Talbott. Sixty 5 1/2-, 6-, and 6 1/2-year-old boys and girls were administered the Berry-Talbott test of language. Twenty adults received the same test. Analyses of variances of children's total scores revealed no differences between sexes and age levels. However, the differences in responses between children and adults, as shown by an item analysis, suggest the presence of a maturational effect but not with the age group investigated. The results indicate that the expected performance levels predicted by Berry and Talbott for this age child as well as some items should be revised. Various hypotheses are offered to explain differences in the response patterns.


Effects of visual deprivation and alterations in binocular competition on responses of striate cortex neurons in the cat. Electrophysiological recordings were made from single neurons in striate cortex of normally reared kittens (group N), kittens raised with binocular lid-suture (group BD), and kittens raised with one eye lid-sutured and other eye removed (group MD-E). The MD-E group represents a condition in which inputs from the deprived eye have been placed at a competitive advantage over those from the other eye. In agreement with previous studies, fewer cells were responsive to visual stimulation in BD kittens than in N kittens. Among the responsive cells, fewer were direction selective, fewer were orientation selective, and more had inconsistent or fast-adapting responses than in normals. The responsiveness and receptive field properties of striate cortex neurons in the MD-E kittens were less affected by the visual deprivation than in BD kittens; however, they still were abnormal in comparison to normal kittens. Comparison of the ocular dominance distributions for cells in N and BD kittens showed a marked reduction in binocularly driven cells in BD kittens. In addition, in BD kittens, a larger proportion of monocularly driven cells had orientation selective receptive fields than did binocularly driven cells. This difference was not found in normally reared kittens. The results of this study suggest that abnormal binocular interactions contribute to the effects of visual deprivation following binocular lid-suture, probably due to asynchronous light-dark inputs through the closed lids. Removing the other eye and placing inputs from the deprived eye at a competitive advantage during development results in decreased effects on striate cortex neurons. Nevertheless, visual deprivation still produces abnormalities in striate cortex independent of asynchronous or uncorrelated visual stimulation of the two eyes.


Calculation of serum digoxin levels in patients with normal and impaired renal function. Serum digoxin levels were examined in 55 patients with varying degrees of renal function impairment who were receiving chronic oral digoxin therapy. Three methods of predicting digoxin serum levels were investigated. Each method may be applied using serum creatinine values and does not require urinary data. Correlations between calculated and actual digoxin levels in combined male and female patients were improved when changes in digoxin distribution volumes in renal impairment were considered. Correlations between calculated and actual digoxin levels were poor in male patients but were again improved by incorporating changes in drug distribution volume. Correlations obtained in female patients were superior to those obtained in male patients and appeared to be independent of the method of calculation employed.


Organization and morphologies of acetylcholinesterase-containing neurons in the thalamus and hypothalamus of the rat. The distribution and morphologies of neurons containing acetyl cholinesterase (AChE, EC 3.1.1.7) in the thalamus and hypothalamus of the rat were studied by means of a pharmaco-histochemical technique involving staining for AChE (Karnovsky-Roots' procedure) at various times after administration of bis-(u-methylethyl)phosphorofluoridate. This method enables visualization of individual AChE-containing neuronal somata and their processes to a degree not possible with other protocols for the enyzme. The strongest AChE activity occurring at the level of the thalamus is found within the small, round to oval, somata of nucleus anterior dorsalis. Most of the intralaminar nuclei, as well as nucleus reticularis, are composed of medium-sized multipolar neurons displaying moderate to strong AChE activity. Moderately stained AChE neurons are also found in pars ventralis of nucleus geniculatus lateralis and in pars lateralis of nucleus habenularis. Most of the neurons of the lateral and posterior thalamic territories, however, are nearly devoid of AChE. At the level of the hypothalamus, the neurons of nuclei supraoptics and paraventricularis show strong AChE activity. The AChE neurons of nucleus supraopticus are surrounded by numerous AChE-containing processes of some large lateral preoptic area neurons that stain intensely for the enzyme. Numerous intensely stained AChE perikarya occur in the lateral, dorsal, and supra-mammillary hypothalmic areas. These neurons often possess several AChE-containing processes. Nuclei arcuatus and ventomedialis consist mainly of neurons displaying a weak to moderate intensity of AChE staining. At the level of the mamillary bodies most neurons show moderate AChE activity except the neuronal somata of nucleus mammillaris lateralis which stain very strongly for the enzyme.


The rabbit optic nerve: fibre diameter spectrum, fibre count, and comparison with a retinal ganglion cell count. This electron microscopic study indicates that the rabbit optic nerve contains 394,000 +/- 20,000 (p less than 0.05) nerve fibers, of which at least 98% are myelinated. The fibre diameter spectrum of the nerve is unimodal and ranges from 0.25-7 mum with its peak at 0.75 mum. The projection of the visual streak fibres is not apparent in local diameter spectra near the optic nerve head. Integration of a ganglion cell density map of the retina from another rabbit indicates a total ganglion cell count lying between 455,000 and 547,000. The optic nerve fibre and ganglion cell counts are both substantially greater than the maximum fibre count previously reported.


Reduction of the naturally occurring motor neuron loss by enlargement of the periphery. Motor hyperplasia following the enlargement of the periphery by implantation of a supernumerary leg is not due to "remote control" of proliferation, as shown by motor neuron counts in 6-day chick embryos. We have tested the alternative hypothesis that we are dealing with reduction of the naturally occurring cell death. In normal development, the lumbar lateral motor column (l.m.c.) undergoes motor neuron degeneration resulting in a cell loss of at least 40%, which occurs between six and one-half and nine and one-half days. Following transplantation of supernumerary legs, cases selected for vigorous motility showed a numerical difference between experimental and contralateral (control) sides amounting to +11.0% to +27.5%. The transplants were innervated by varying combinations of thoracic and rostral lumbar nerves. We interpret our data in terms of survival of motor neurons which normally would have failed in a competition at the periphery but which were sustained by the enlarged peripheral fields. Our data do not permit a decision between the two alternatives: competition for synaptic sites or for a trophic agent. The surviving motor neurons are not limited to the rostral segments of the motor column but in most instances distributed along its entire rostro-caudal extent, implying a redistribution of all l.m.c. axons. The term "hyperplasia" is no longer appropriate for the phenomenon under consideration and should be replaced by the term "hypothanasia.""


Circulatory effects of diazepam in heart disease. Diazepam was administered to ten patients with heart disease during diagnostic cardiac catheterization, in order to determine whether or not this drug's circulatory actions could alter results obtained during the procedure. Diazepam produced no change in baroreceptor sensitivity; however, there was a significant rise in heart rate and a significant fall in aortic systolic and left ventricular end-diastolic pressures. Cardiac index was unchanged, whereas stroke volume fell significantly. Systemic vascular resistance and peak left ventricular dp/dt did not change throughout the study. Clinical response in terms of sedation was judged to be satisfactory in eight patients, and no adverse effect on respiration was noted. Diazepam has little effect on basal circulatory and respiratory parameters when changes in these parameters are averaged for our ten patients. However, substantial changes in hemodynamic parameters did occur in several individuals, and such alteration in circulatory function must be considered when this agent is used routinely in patients having diagnostic cardiac catheterization.


A fine structural and E-PTA study of photoreceptor synaptogenesis in the chick retina. Photoreceptor synaptogenesis in the embryonic and hatchling chick retina was studied with conventional EM techniques and ethanolic phosphotungstic acid (E-PTA). The photoreceptors line up between 11 and 13 embryonic days with their undifferentiated synaptic bases facing the outer plexiform layer (OPL). E-PTA staining at 11 embryonic days does not reveal any para-membranous specializations of the receptors but numerous stained punctae adhaerentes are observed in the OPL. At 13 embryonic days neurites of presumed bipolar and horizontal neurons are aligned parallel to the bases of the receptors and cytoplasmic protrusions of the receptors project between some of these neurites to form dyad appositions. An osmiophilic undercoating, which is not E-PTA positive at this time, is present on the cytoplasmic face of the receptor membrane in these apposition regions. Between 13 and 15 embryonic days the filopodial protrusions of the receptors continue to elongate further and become aligned with neurites in dyad and triad appositions. The osmiophilic undercoating now extends along the entire inner surface of the receptor pedicle protrusions and becomes E-PTA positive. Between 15 and 17 embryonic days focal aggregations of osmiophilic and E-PTA stained material appear along the membranes of the protrusions and there is some E-PTA staining of the postsynaptic densities and intervening cleft material. Between 17 and 21 embryonic days mature ribbon synapses are observed on the surfaces of the conical-shaped, receptor pedicles where the ribbons and their synaptic vesicles are associated with the dense aggregations (arciform densities), seen earlier as isolated focal aggregations, and the receptor undercoating is restricted to non-synaptic regions. E-PTA staining shows that ribbons are positively stained around their borders only and that they are contiguous with the intensely stained arciform densities. The cleft material and postsynaptic densities of some synapses first stain as V-shaped junctions and later as Y-shaped junctions. These observations suggest that ribbon synaptic junction formation begins with an alignment of pre- and postsynaptic membranes and the presence of the receptor presynaptic membrane undercoating, followed by the appearance of the presynaptic arciform densities and some staining of the cleft material and postsynaptic densities. These events are followed by the appearance of synaptic ribbons which are associated with the presynaptic arciform densities and by a further differentiation of the cleft material and postsynaptic densities.


Aminoglutethimide in the treatment of Cushing's syndrome. The efficacy and tolerability of aminoglutethimide for the treatment of Cushing's syndrome was assessed in 66 cases three of which are described in the present paper. Aminoglutethimide provided palliation from the signs and symptoms of hypercorticism in 13 of 21 patients with metastatic adrenocortical carcinoma and four of six patients with ectopic ACTH production due to metastatic carcinomas. All six of the patients with adrenal adenomas showed clinical and biochemical improvement, while 14 of the 33 patients with bilateral adrenal hyperplasia of pituitary origin improved. Adverse reactions attributed to aminoglutethimide such as drowsiness, rash, and nausea occurred in 58 per cent of cases. These data suggest that aminoglutethimide has a place in controlling the signs and symptoms of adrenocorticoid excess in patients with Cushing's syndrome due to malignancy and is effective preoperative therapy for patients with adrenal adenomas and bilateral hyperplasia.


An ultrastructural morphometric study of mossy fiber endings in pigeon, rat and man. Mossy fiber endings and their synapses have an increasing morphological complexity along the phylogenetic scale which is specially evident when the evolution from reptiles to birds is considered. Among birds and mammals, only scanty and merely qualitative differences have been noticed in the mossy fiber organization. In the present study, the mossy fiber endings organization within the neuropil of four pigeons, four rats and six men was studied at optic and ultrastructural levels using morphometric methods. No significant differences were found in the fraction of volume of the neuropil and in the number of granule cells per unit volume of granular layer in all the three species. In man, a significant decrease in the volume of mossy fiber endings per unit volume of neuropil, and significant increases in their surface-to-volume ratio, in the fraction of their neurolemma occupied by synaptic contacts and in the average length of their synaptic contact zones, were found. The total synaptic area of mossy fiber endings per unit volume of neuropil was larger in man than in other animals in spite of their more reduced volume. These results show that significant differences in mossy fiber organization can be demonstrated when man is compared with a small mammal (the rat) and a bird (the pigeon). It is suggested that differences in the stereological organization of man's terminals might be related to his capacity for making finely graded movements. Moreover, it is suggested that the phylogenetic evolution of the mossy fiber organization has progressed among the higher vertebrates as it did in the rest of the animal scale.


The connective tissue coverings of leech peripheral nerves: anatomical evidence for the absence of cerebrospinal fluid in the leech. The central nervous system of Hirudo medicinalis is contained within a blood vessel, the ventral longitudinal sinus, but the nervous system is separated from the blood by the visceral endothelium. The visceral endothelium possesses many pinocytotic vesicles and basal infoldings and thus appears active whereas the parietal endothelium appears inactive. The junction between the visceral and parietal endothelia is abrupt. Peripheral nerves in this animal, as in vertebrates, are covered by endoneurium, perineurium, and epineurium. The endoneurium is continous with the fibrous tissue of the segmental ganglia. The perineurium, consisting of a single layer of flattened cells that surrounds the peripheral nerve like a sleeve, is not continuous with the endothelium of the ventral sinus, but is separated from it by 5-10 microns. Therefore, at the point where the peripheral nerve joins the segmental ganglion, the extracellular spaces of the central nervous system, the peripheral nervous system, and the body wall are all confluent. Thus, there are only two compartments of the extracellular space in the leech: the blood, which is enclosed by the endothelia of the coelomic sinuses, and the extracellular fluid of the body, which includes the extracellular fluid of the nervous system. There seems to be no equivalent of cerebrospinal fluid in the gnathobdellid leech.


Retinofugal pathways in two marsupials.

Retinofugal pathways in two marsupials. Autoradiographic and anterograde degeneration tracing methods were used to study and compare the organization of retinofugal pathways in two marsupial opossums, Didelphis virginiana and Marmosa mitis. Seven identical retinal targets were demonstrated for each opossum. These include: (1) the suprachiasmatic nucleus of the hypothalamus, (2) the dorsal and (3) ventral lateral geniculate nuclei, (4) the lateral posterior nucleus, (5) the pretectal complex, (6) the superior colliculus and (7) the accessory optic nuclei. While the pattern of retinal input to six of the seven targets was quite similar in the two species, the organization of the retinogeniculate pathways exhibited striking differences. In particular, our autoradiographs reveal no separation of ocular inputs within the lateral geniculate nucleus of Didelphis, i.e. the ipsilateral input is overlapped completely by the more extensive contralateral projection. In contrast, there is considerable separation, as well as overlap, of the occular inputs within the lateral geniculate nucleus of Marmosa. Our autoradiographs reveal several distinct bands of label within each geniculate nucleus, and upon superimposing the nuclei, ipsilateral and contralateral to the placement it is apparent that two of the bands overlap, while five do not (three ipsi, two contra).


Anatomical and behavioral analysis of hippocampal cell fields in rats. For a study of the structure and function of the different hippocampal cell fields, a surgical approach was devised that permitted selective damage to either the hippocampal subdivisions or the major efferent projections. Neuroanatomical techniques were used in Experiment 1 to verify the selective nature of the lesions and to provide information concerning differential hippocampal projections. In Experiment, 2, rats with selective hippocampal lesions were tested on a series of tasks chosen to measure various aspects of behavior. Animals with fimbrial lesions interrupting connections between the CA3-CA4 cell fields and the septal region were similar to animals with extensive hippocampal lesions in being more active than the other groups at night, more active during the day, and more affected by deprivation. In addition, both groups were facilitated in acquisition of a shuttle box avoidance task. Extensive damage to the hippocampus and more selective damage to the CA1 pyramidal cell field resulted in impaired spatial reversal learning. The results are interpreted as providing support for the view that the two main subdivisions of the hippocampus, the CA1 and CA3-CA4 cell fields, are differentially involved in behavior.


Lateral hypothalamic syndrome in rats: a comparison of the behavioral and neurochemical effects of lesions placed in the lateral hypothalamus and nigrostriatal bundle. The effects of total (T-NSB) and subtotal (S-NSB) destruction of the nigrostriatal bundle were compared with the effects of large lateral hypothalamic (LH) lesions on various aspects of the lateral hypothalamic syndrome. The T-NSB and LH lesions produced equivalent decreases in caudate and telencephalic contents of dopamine and norepinephrine, while with the exception of telencephalic dopamine, S-NSB lesions had consistently smaller effect. The T-NSB and LH lesions produced equivalent effects on duration of aphagia and adipsia (Stages 1 to 3) and on long-term decreases in body weight and ad lib water consumption, and these effects were always greater than those produced by the S-NSB lesion. These aspects of the lateral hypothalamic syndrome appeared to be related to the interruption of the nigrostriatal bundle and consequent decrease in caudate dopamine. The T-NSB and S-NSB lesions produced equivalent long-term deficits in water regulation as measured by drinking in the absence of food or in response to intra- and extracellular dehydration, but these deficits were always significantly less than those produced by the LH lesion. It was concluded that these regulatory deficits were not related to destruction of catecholamine pathways. All three lesions totally blocked eating in response to a glucoprivic challenge. This aspect of the lateral hypothalamic syndrome, therefore, results from destruction of a small portion of the lateral diencephalon and may be related to the interruption of the dopaminergic mesolimbic system.


Preweanling rats: recovery from lateral hypothalamic damage. Preweanling male and female albino rats sustained lateral hypothalamic area (LHA) destruction at 10 days of age. Pups with bilateral LHA destruction (Bi-LHA) displayed the lateral hypothalamic recovery syndrome (LHRS) and recovered voluntary feeding and drinking between 44-75 days of age. The Bi-LHA rats of both sexes showed permanent deficits (through 200-275 days of age) in responding to hydrational challenges and did not feed in response to 2-deoxy-D-glucose treatment. Male Bi-LHA rats' body weights were permanently depressed by 20%-25%, whereas female body weight depression was only temporary. Rats sustaining LHA destruction on one side of the brain (Uni-LHA) displayed an abbreviated LHRS, recovering voluntary feeding and drinking by 25-32 days of age. The Uni-LHA rats showed some permanent deficits in responding to hydrational challenges, yet they displayed the same sex differential for body weight regulation as the Bi-LHA rats. The results of this investigation demonstrate nearly identical effects of LHA destruction whether sustained preweaning, postweaning, or during adulthood.


Strain differences among chickens in tonic immobility: evidence for an emotionality component. Substantial strain differences in tonic immobility were found between different breeds of chickens. Crossbreeding between strains showing different immobility durations yielded hybrids that exhibited intermediate reactions. For purpose of relating the strain differences in tonic immobility to more conventional measures of emotionality, data were collected on open-field activity, defecation, and adrenal weight. Overall, the results implicated strain-specific differences in emotionality as being the basis for the observed differences in immobility. Latency to defecate in an open field, however, was highly correlated with latency to ambulate. It was argued that defecation, rather than being an absolute measure of fear or emotionality, may in fact be an intermediate response to gradual fear reduction.


Neonatal thyroxine stimulation accelerates the maturation of both locomotor and memory processes in mice. In two experiments mice were injected with thyroxine on Postnatal Days 1, 2, and 3, and the subsequent effects upon the development of the swimming reflex and the emergence of instrumental learning/memory processes were examined. In agreement with past studies, early thyroxine treatment accelerated the maturation of swimming capacities and general physical development compared with littermate controls receiving saline injections. In the second study, thyroxine- and saline-treated mice received 25 training trials on a shock-escape T-maze taks at 7, 9, 11, or 13 days of age with a retention test 24 hr later. The results indicated that while learning was equivalent within each of the ages between the treatment groups, onset of 24-hr retention capacity occurred approximately 2 days earlier in the thyroxine-treated mice than in controls. In addition, a performance deficit was observed in the thyroxine mice at the oldest age tested, in agreement with previous reports. The results of these experiments suggest that early hyperthyroidism results in earlier maturation of both locomotor and memory processes, followed by later performance deficits.


On the retinal mediation of genetic influences in color preferences of Japanese quail. The hypothesis that the pigmentation of retinal oil droplets is the morphological target of genetically induced change in the early color preferences of the Japanese quail (C. coturnix japonica) was examined and rejected. Subjects were drawn from the fourth generation of genetic selection for preferences between blue and red, and they were compared according to genetic lines of origin and the presence or absence of pigmentation in their retinal oil droplets. Pigmentation was manipulated by raising parents on carotenoid-free diet. Results indicate a uniform shift toward red preference in all subjects with history of carotenoid deprivation regardless of genetic background, and no change in the magnitude of differences between genetic lines. The data suggest that retinal oil droplets mediate intensity discrimination in the photopic range rather than the perception of variations in light wavelength.


Perceived intensity of peripheral thermal stimuli is independent of internal body temperature. Four adult male human subjects were tested under three conditions of internal body temperature: hypothermia, normal, and hyperthermia. Under each of these conditions, they judged the intensity (degree of warmness or coolness) and the hedonic quality (degree of pleasantness or unpleasantness) of a series of stimuli ranging from hot to cold. The results showed that whereas hedonic quality is greatly influenced by the value of internal body temperature, the perception of warmness or coolness is independent of internal temperature and dependent only on peripheral stimulation.


Conditioned adrenocortical steroid elevations in the rat. An illness-induced taste aversion paradigm was used to condition an elevation in plasma corticosterone level. Rats were injected with cyclophosphamide 30 min after consuming a novel saccharin drinking solution. Plasma corticosterone levels were measured before conditioning to determine unconditioned steroid levels and 3 and 6 days after training when conditioned and nonconditioned animals were provided with the saccharin solution or plain water, or were left deprived. The pairing of saccharin and cyclophosphamide was effective in inducing a passive avoidance response. There were no differences between the steroid levels of conditioned and nonconditioned animals supplied with plain water or those that remained deprived, although deprivation increased corticosterone levels. Nonconditioned rats presented with saccharin had steroid levels that did not differ from control values. Conditioned animals presented with saccharin showed an elevation in steroid level which was significantly greater than that observed in any other group. Comparable results were obtained when LiCl was used as the unconditioned stimulus.


Conditioned hypoglycemia.

Conditioned hypoglycemia. An experiment was conducted to determine whether conditioned hypoglycemia would develop in rats that never became hypoglycemic on the conditioning trials. Rats were given saline, insulin, glucose, or glucose plus insulin as the unconditioned stimulus in a classical conditioning paradigm. It was found that a change of blood glucose need not occur on the conditioning trials in order to obtain successful conditioning of a hypoglycemic response; rather, an increase of insulin was all that was necessary. An explanation of conditioned hypoglycemia as the logical response of glucoregulatory centers of the central nervous system is proposed.


Familial generalized dyschromic amyloidosis cutis. A generalized form of primary cutaneous amyloidosis was found in two siblings when microscopic examination was carried out on areas of scattered hypopigmentation. Multiple biopsies from different sites of the skin suggested that the pigmentary disorder was probably a process independent of the amyloidosis. One of the siblings died of interstitial pulmonary fibrosis, congenital pulmonary stenosis and diabetes mellitus. Post mortem examination of the lungs showed the presence of few amyloid deposits in the diffusely fibrotic tissue, suggesting that these were secondary to the chronic pulmonary disease. Because of the absence of amyloid involvement in parenchymatous organs and the absence of cutaneous signs of systemic amyloidosis as macroglosia or petechiae, this case suggests that primary cutaneous amyloidosis is distinctly different from the cutaneous manifestation of primary systemic amyloidosis.


Subepidermal calcified nodule. Report of a case with apparent hair follicle origin. A subepidermal calcified nodule occurred on the face of a 15-year-old Negro boy. Histological examination revealed its apparent origin in mature and immature hair follicles. Previous reports suggest that subepidermal calcified nodules may arise in nevi or in sweat glands. An additional finding in this case was transepidermal elimination of calcium.


Studies on etiologic factors in pemphigus. A survey of 234 cases of pemphigus yielded three observations which suggest that different forms of pemphigus may have different etiologies. 1. While the incidence of pemphigus in the age group of 21 and over was essentially the same in males and females (108 and 113) the incidence was significantly higher in females in the age group under 20. Only two of 13 patients in this group were males. Also pemphigus foliaceus and erythematosus was reported in a significantly higher proportion of the cases in the age group of 2 1/2 to 20 thus suggesting that the juvenile form of the disease differs from the adult form. 2. In  four of a group of 15 cases identified as pemphigus foliaceus the disease appeared to be provoked by minor physical insults, a frequency which is significantly higher than the five cases with similar histories in the group of 198 cases identified as pemphigus vulgaris. 3. In the entire group of 234 cases two patients with pemphigus both proven by immunofluorescence had relatives with pemphigus. Also a third patient had a blood relative with bullous pemphigoid. This frequency of three per 234 is higher than would be expected by chance. Studies of one family (not included in this survey) with multiple skin antibodies suggest that such familial predispositions may be due to abnormal immune responses.


Tubular apocrine adenoma.

Tubular apocrine adenoma. Two cases of tubular apocrine adenoma were studied by light, histochemical, and electron microscopic methods. This benign apocrine hamartoma must be considered in the classification of appendage tumors, particularly those associated with organoid epithelial nevus, and may be confused with metastatic adenocarcinoma. The tumor is characterized by dermal and subcutaneous lobular masses of tubular structures. Connection to the epidermis by one or more ductlike structures is observed. The tubules contain typical apocrine epithelial cells, some with hyaline or clear cell differentiation. The tumor cells have apocrine differentiation by histochemistry and ultrastructure. The localization to the scalp and the nodular, lobulated appearance and the apocrine structures indicate that this tumor is similar to nevus syringocystadenoma papilliferum and must be diffentiated from it.


The influence of dietary protein intake on milk production and blood composition of high-yielding dairy cows. Cows were fed either 75 or 100% of the recommended intake levels for protein and 100% of recommended energy levels (Agricultural Research Council, 1965) from 8 weeks pre-calving until 14 weeks post calving. From 14 weeks post calving and to the end of lactation all the cows received 100% of the recommended protein and energy intakes. The mean of the 305-d milk yields of the 2 groups was not significantly different and although cows on the lower protein intake produced less lactose during the first 14 weeks of lactation there was no significant difference in total lactose, fat, protein or total solids production between the groups. In both groups blood packed-cell volume, red cell count and haemoglobin decreased during the first 10 weeks of lactation and then began to increase in the high-protein group. The cows receiving the low-protein diet showed a similar increase only when they received the high-protein ration from 14 weeks post calving. The mean interval from calving to conception was 27-5 weeks in the high-protein group and 20 weeks in the low-protein group. It is concluded that feeding 75% of protein requirements to dairy cows during the first 14 weeks of lactation does not reduce milk yield or quality significantly and probably has no adverse effect on fertility.


Reproducibility of electronic cell counts in milk; a study of 5 further factors. This paper is a sequel to a previous one in which a number of factors likely to influence the accuracy of counting somatic cells in milk was assessed; in the present work the effects of 5 other factors are investigated. In a study of storage time and temperature of milk samples fixed in formalin, a significant increase in cell count occurred after 5-7 d when samples were stored at room temperature (17-23 degrees C), compared with those maintained at 4 degrees C. When manual and mechanical mixing of fixed samples were compared only marginal differences in cell counts were observed. An increase in cell counts followed manual dilution of milk samples in comparison with automatic dilution. The temperature of samples prepared for counting was also studied and no significant variations occurred between mean temperatures of 12-7 and 32-9 degrees C. The final factor evaluated was that of holding time before counting; using 4 cell-count levels it was observed that counts were acceptable up to 1 1/2 h.


Compositional and electrophoretic changes in buffalo milk-fat globule membrane proteins during lactation. Chemical analyses, polyacrylamide-gel electrophoresis and isoelectric focusing of milk-fat globule membrane proteins (FGMP) obtained from the milk of 2 Murrah buffaloes were done to determine if any change in composition occurred during lactation. Changes in the levels of sialic acid, hexose, hexosamine, N and P were found in the FGMP obtained at different stages of lactation. On the day of parturition, 8 major proteins in FGMP were determined by sodium dodecyl sulphate polyacrylamide-gel electrophoresis whereas 6 major proteins were obtained in FGMP of middle and late lactation milks. Isoelectric focusing of FGMP showed 8-9, 9-13 and 13-16 proteins from colostrum, middle and late lactation milks, respectively and the isoelectric pH of the proteins varied from 5-25 to 7-80, 5-85 to 8-30 and 5-75 to 8-61 respectively.


A study of cow's milk containing high levels of linoleic acid: isolation and properties of the fat-globule membrane. Properties of whole milk and milk fractions from cows fed a diet that gave a greatly increased proportion of unsaturated fatty acid residues (especially of linoleic acid) in the milk lipids were studied, and this milk (high-linoleic milk) was compared with milk from cows on a control diet (control milk). The milk fractions were isolated by high-speed centrifugation of whole milk or cream and were examined by chemical analysis and electron microscopy. During centrifugation the globules of milk fat were disrupted and the membranes (fat-globule 'ghosts') floated as a layer beneath the free lipid. Membrane proteins from the 2 sorts of milk gave the same electrophoretic pattern and the amino acid compositions were the same. Lipid analysis of the membrane fraction from high-linoleic milk showed the expected increase in the proportion of unsaturated fatty acid residues in the neutral lipids, but there was an unexpected decrease in the proportion of unsaturated residues in the membrane phospholipids. No differences were found between high-linoleic and control milk in the ultrastructure of the milk-fat globules or the isolated membranes.


Isolation, preparation and the amino acid composition of 4 milk-fat globule membrane proteins solubilized by treatment with sodium dodecyl sulphate. Milk-fat globule membrane (MFGM) proteins were solubilized by treatment with SDS. Four of the major proteins were isolated as SDS complexes using column chromatography. The purity of each isolate was determined by SDS polyacrylamide gel electrophoresis and sufficient of each protein was obtained for amino acid analysis. The amino acid compositions of the isolated MFGM proteins and a total MFGM protein extract were determined. Differences in amino acid composition were found in particular between the major MFGM glycoprotein and the other 3 membrane proteins. The relationships of the amino acid composition to protein properties and structure are discussed.


Distribution of isomeric octadecenoic fatty acids in milk fat. Milk fat octadecenoic acids were isolated by preparative gas-liquid chromatography of their methyl esters and separated into cis and trans isomers by argentation thin-layer chromatography. The distribution of the double bonds in the two fractions was determined by reductive ozonolysis. Cis octadecenoic acids had double bonds in positions 6 to 14. The cis-9 isomer was the most abundant isomer representing approximately 95% of the total. Trans octadecenoic acids had double bonds in positions 6 to 16, the predominant isomer being trans-11 octadecenoic acid. Data illustrating the range of variation in the distribution of positional isomers of octadecenoic acid for herd milk fat and butter are presented. There was no obvious seasonal variation in the distribution pattern. Fat from perirenal and subcutaneous adipose tissue of a dairy cow had composition similar to that of butter samples.


Recovery and nutritional evaluation of proteinaceous solids separated from whey by coagulation with chitosan. Chitosan, a cationic carbohydrate polymer manufactured from chitin in shrimp and crab wastes, coagulated suspended solids in cheese whey as effectively or more so than ten commercial synthetic polymers. Concentrations of suspended solids after settling were reduced over 90% by coagulation at pH 6.0 with a ratio of chitosan to suspended solids of 2.15% (1:46.5). The yield of coagulated solids was approximately 2,270 mg/liter. The proximate composition of the coagulated solids after freeze drying was 73% protein, 6% lactose, 10% ash, and 7% moisture. Without the aid of a coagulating agent, setting for 1 or 3 h reduced suspended solids by only 34% and 49%, respectively. Rat feeding studies showed nn significant differences in the protein efficiency ratio of casein, coagulated whey solids  containing chitosan, and whey solids containing no polymer. These results provide evidence of utility for coagulated whey solids as a protein supplement.


Comparative production of beta-lactoglobulin and orotic acid with lactose in bovine mammary cell cultures: effects of cell density and constituent inhibition. Abilities to accumulate beta-lactoglobulin and ortic acid were compared to lactose in dispersed cell cultures of lactating bovine mammary tissue. The inverse of the amount accumulated of each milk constituent at a given time in the culture medium was a linear function of the inverse of the cell density. The amount of lactose had no effect on its own subsequent accumulation, but added orotic acid and beta-lactoglobulin inhibited their own production. The accumulation of certain milk constituents in the culture medium is a factor in the expression and loss of normal function in the in vitro cultures which may be related to the observed effects of milk accumulation in vivo on the rate of milk synthesis and mammary involution.


Glucocorticoid binding in mammary tissue slices of cattle in various reproductive states. Unlabeled cortisol and dexamethasone reduced tritiated cortisol and tritiated dexamethasone binding to 700 X g supernatant and precipitate fractions of mammary tissue slices from virgin heifers and from multiparous cows that were 1-mo prepartum (nonlactating), lactating (non-pregnant), or dry (nonpregnant, nonlactating). Unlabeled progesterone, testosterone, and 17beta-estradiol had no effect on tritiated glucocorticoid binding in 700 X g supernatant and precipitate fractions from these mammary tissue slices. The 700 X g fractions in mammary tissue slices from all cattle bound cortisol and dexamethasone with high affinity (Kd 10-10M). There were 1263 and 1955 molecules of cortisol and dexamethasone bound per mammary cell, respectively, in mammary tissue slices from lactating non-pregnant cows; in comparison virgin heifers bound 413 and 651 molecules of cortisol and dexamethasone; dry, non-pregnant cows bound 336 and 536 molecules of cortisol and dexamethasone; and 1-mo prepartum nonlactating cows bound 532 molecules of cortisol. Mammary tissue slices from cattle in reproductive states examined contained a major non-specific component which bound cortisol in both 700 X g tissue fractions. Since mammary tissue slices from lactating cattle bound more molecules of glucocorticoids than mammary slices from cattle in other reproductive states, we speculate specific glucorticoid binding may be associated with lactation.


Protein and methionine hydroxy analog for lactating cows. A 2 X 2 factorial experiment (protein 12.5 and 15.5; methionine hydroxy analog 0 and .125% dry matter) included 144 cows for one complete lactation, distributed over seven locations. Rations were formulated to the desired protein, methionine analog, and constant amounts of fiber 17%, sulfur .225%, calcium .6%, phosphorus .4%, and salt .5%. Treatment effects were not apparent for dry matter intake, daily milk and fat-corrected milk production, conversion of energy, and body weight changes. Conversion of dietary crude protein into milk protein was 34.5% for the low and 25.8% for the high protein ration. Methionine analon (0% = 2.54; .125% = 1.90). Effect of methionine analog was most apparent at low protein as 0 analog cows produced 247 kg fat, required 2.9 services/contraception, and had 156 days open whereas cows on other treatments (.125% analog and/or high protein) produced 264 kg fat, required 1.8 to 2.2 services/conception, and had 124 to 134 days open. Methionine analog response is discussed in relation to tuminal and postruminal effects as well as the interrelation with protein and energy.


Relationship of milk secretion to hypocalcemia in the dairy cow. After parturiton, alternate periods of milking for 4 days and nonmilking for 3 days produced marked changes in plasma concentrations of calcium, phosphorus, magnesium, chloride, and parathyroid hormone in Jersey cows. A 3- to 4-day period of hypocalcemia, increased parathyroid hormone concentrations, hypophosphatemia, and hypermagnesemia was associated with initiation of each milking period. These measurements did not return to normal until 6 to 7 days after initiation of milking. An "overshoot" of the calcium and phosphate concentrations after this adaptive period occurred in many of the cows. There was little difference in the time sequence of the hypocalcemic period that was associated closely with parturition and initiation of milk secretion in the cow and of hypocalcemic periods that could be induced by the alternate periods of milking. A "lag time" in the calcium homeostatic mechanisms of the cows was present, and for the calcium demand placed on the cows in these experiments the "lag time" was 5 to 7 days. This "lag time" appears to be important in development of parturient by hypocalcemia of dairy cows.


Selenium and vitamin E and incidence of retained placenta in parturient dairy cows. II. Prevention in commercial herds with prepartum treatment. In a series of field experiments in Ohio involving 193 parturient cows of the Holstein and Guernsey breeds, the prophylactic efficacy of selenium and vitamin E was tested under field conditions. Herds initially were chosen because of a chronic problem with retained placenta which could not be related to a known etiological factor. Each herd was divided into three groups. Group A received an injection of 50 mg of sodium selenite 40 days prepartum and 680 units of alpha tocopherol acetate followed by the same treatment 20 days prepartum. Group B received a single injection of 50 mg of sodium selenite 20 days prepartum, and 680 IU of vitamin E. Group C served as the control. Incidence of retained placenta was reduced from a mean of 51.2% in control cows to 8.8% for animals injected with selenium and vitamin E. No differences in efficacy were between Group A and B, and it appears that the single 20 day prepartum injection of 50 mg of sodium selenite and 680 IU of alpha tocopherol acetate is an effective prophylactic for prevention of retained placenta.


Absorption of zinc from small and large intestine of calves. Calves fed a high-zinc diet were used to study zinc absorption from various sections of the small intestine. Absorption was determined by measuring zinc-65 in various tissues and plotting the tissue concentrations against dosing site, expressed as percentage of intestinal length. Zinc absorption, per unit of intestinal length, was similar throughout the small intestine and was as great in the distal as in the proximal end. Apparently, early researchers using isolated loops and everted sac techniques failed to recognize rate of digesta passage and tissue homeostasis as major factors associated with zinc uptake when they concluded that the duodenum was the primary site of zinc absorption. The data show that the duodenum is not the major site of zinc absorption in calves regardless of dietary zinc. In a separate experiment, zinc-65 was injected directly into the large intestine of calves fed a low zinc diet. Only about 2% of total zinc absorption was from the large intestine.


Screening tests for new teat dips.

Screening tests for new teat dips. Increased use of after-milking teat dips has resulted in the appearance of many new teat dips and a need for methods of evaluation of efficacy. A method was developed for determining the ability of a disinfectant to kill bacteria on the teat ends. Results from several known efficacious products indicated an approximate 95% reduction in bacterial flora. Additional data are presented on some experimental products. This method will provide a measure of effectiveness of a producton teat-skin disinfection. The effect of some changes in the testing procedure on bacterial reduction is demonstrated: 1) Increased times between inoculation and dipping and between dipping and swabbing tended to decrease recoveries on control teats. 2) Saline dips on controls teats provided increased recoveries of test organisms.


Factors affecting calcium, phosphorus, and magnesium status of dairy cattle on the Oregon coast. Blood plasma from 126 milking cows in 21 herds was analyzed for calcium, phosphorus, and magnesium in October, 1974, and in the following April. For all three minerals, time of sampling, herds, and time of sampling by herd differed. Mean values in October and April were calcium, 10.1 and 9.0; phosphorus, 5.96 and 4.88; magnesium, 1.98 and 1.85 mg/100 ml. Calcium also differed between stages of lactation. Mean calcium for cows milking less than 100 days, 101 to 200 days, and greater than 200 days and dry was: 9.41, 9.70, and 9.80 mg/100 ml. Differences in winter feeding practices among herds were responsible for time of sampling, herd, and time of sampling-by-herd differences.


Absorption, excretion, and tissue deposition of titanium in sheep. Titanium metabolism was measured in three 18 kg lambs each fed 450 g chopped hay daily. Two of the lambs were dosed orally and one intravenously with 3 muCi titanium-44 each. Clearance of the intravenous dose was extremely slow; after oral administration, however, no titanium-44 was detected in blood plasma for 48 h. Over 96% of the oral dose was recovered in feces and digestive tract contents. Titanium-44 absorption, estimated from total carcass recovery and by comparison of concentrations in internal organs of orally and intravenously dosed lambs, was less than .5%. Fecal titanium could be a satisfactory index of soil ingestion by grazing ruminants.


Testosterone and libido in holstein bulls of various ages. Testosterone was measured by radio-immunoassay in the blood plasma collected from 197 and 195 Holstein bulls in the spring and fall seasons, respectively. Bulls ranged in age from 8 mo to 13.5 yr. The average value for spring was 8.0  ng/ml, higher than the value of 5.7 ng/ml in the fall. Also, there was a tendency for testosterone to increase with age of the bulls up to 6 to 7 yr. The concentration of circulating testosterone was unrelated to libido or semen quality.


Fertility of bull semen frozen with beta-amylase, beta-glucuronidase, and catalase. "Capacitase," a product combining beta-amylase and beta-glucuronidase, was compatible with survival of bull spermatozoa frozen in whole milk-glycerol extender at final concentrations per ml of 0, 5, 10, and 20 mug of beta-amylase combined with 0, 75, 150, and 300 units of beta-glucuronidase, respectively. Bull semen was frozen in whole milk-glycerol extender containing the three lower concentrations of enzymes tested in the previous trial and used to inseminate 9057 first-service cows within 4 mo of freezing. The 60- to 90-day percent nonreturns were 74.6, 75.6, and 75.0. The same treatments plus a fourth one containing 10 mug of catalase per ml were fertility tested in another trial. Insemination of 16,842 cows resulted in 75.6, 74.1, 74.6, and 74.2% nonreturns. In this trial semen was held immersed in liquid nitrogen and distributed for immediate use each mo for 6 mo. There was no change in fertility during 6 mo of continuous storage at --196 C. Under the conditions tested neither catalase nor beta-amylase with beta-glucuronidase enhanced fertility of frozen bull semen.


Tumor conference No. 9. Massive hemangioma with pharyngeal involvement. When first seen in May, 1974, this 7-week-old child presented a rapidly enlarging hemangioma involving her face, scalp, oral mucous membranes and pharynx. Because of the development of stridor and complete closure of the eyelids of one eye by the hemangioma, the child was placed on systemic corticosteroid therapy. This was continued for a three-month period at which point it was discontinued. There was unquestionalbe shrinkage of the tumor during therapy. The stridor disappeared and the eyelids opened within a few days. Within six days of discontinuation of the corticosteroids, there was sudden enlargement of the lesion and reappearance of stridor which again subsided after a six-week course of systemic corticosteroids. Currently, the child is still under observation. It is anticipated that further spontaneous resolution will take place but that she will require plastic surgery for some of the residual deformities. The questions of ocular involvement, cardiac enlargement, occlusion of the pharyngeal airway, and arteriovenous anastamoses were raised in this child. Newer treatments including embolization treatments and cryotherapy were considered for this child but were not pursued since the growth of the hemangioma came to a virtual standstill and the child is otherwise thriving.


Treatment of portwine marks by an argon laser. Although the treatment of the ordinarily incurable portwine birthmark by lasers has been practiced for more than 10 years, recent therapeutic investigations have been carried out particularly with the argon laser. Argon lasers now available for medical purposes produce treatment spots that are small. For certain practical reasons, at present, only relatively small portwine marks can be treated effectively. With trained personnel and proper safety measures, the treatment is safe for the patient and the operator. The treatment as yet is not proved to be better with the argon laser because the ruby laser and even an incoherent infrared thermal coagulator can produce similar and often larger cleared areas. It is recommended for the present that treatment of portwine marks by argon lasers be restricted to investigation in medical centers where critical evaluations, control studies, and more powerful laser systems can be developed.


M-plasty techniques.

M-plasty techniques. Conventional closure of surgical defects in skin may cause unsightly protrusions (dog ears). Fusiform excisions with angles of 30 degrees or less reduce protrusion but may require excision of larger volumes and lengths of healthy skin and subcutaneous tissue than may be desirable. M-plasties reduce these requirements while still allowing use of 30 degrees angles at maximum. Applications and technical details are described and illustrated.


Cosmetic surgery of the neck as an office procedure. A simple office procedure to eliminate permanently double chin deformity and senile neck cords and with nearly invisible scars is described. Postoperative complications are mitigated by the use of autogenous fat grafts and constant aspiration of the wound cavity both during and after surgery. Most patients are able to resume their normal activities in several days.


Microtopography of the skin and scar formation. The surface microtopography of normal human skin varies from one anatomical region to another. The patterns at different sites are considered to reflect different orientations of dermal fibers. A simple technique is described that enables such orientations to be accurately delineated. Various scars resulting from lacerations, surgical incisions, and steroid-induced striae were examined in the manner described.


Squamous-cell carcinoma of the penis.

Squamous-cell carcinoma of the penis. Excision of penile carcinoma by chemosurgery (Hohs' technique) is as nearly ideal as can be because it assures removal of the neoplasm with maximal preservation of normal tissue and function.


Dermabrasion for adenoma sebaceum.

Dermabrasion for adenoma sebaceum. Two patients with tuberous sclerosis but without mental retardation were dermabraded for adenoma sebaceum. The treatment was effective and cosmetically satisfying.


The corticosteroid dose graph. Use in determination of corticosteroid requirements, characterization of patients, and prevention of seasonal exacerbation in corticosteroid-dependent patients. Sixty-three corticosteroid(CS)-dependent asthmatics were evaluated by a method which records asthmatic exacerbations as a function of change in CS dosage. This method, the Corticosteroid Dose Graph (CSDG), is a graphic representation of the patients' narrative charts. It is useful in assessing and directing the care of these patients and in evaluating the efficacy of altered therapeutic regimens in asthmatics. The CSDG categorizes cooperative patients (CP) and distinguishes these patients from those who are less cooperative (LCP). Evaluation of the progress of CP by the graphic analysis system showed that CP have fewer severe exacerbations of asthma than LCPs. Evaluation of the 63 patients by this graphic method shows a significantly increased incidence of asthmatic exacerbations in the Chicago area in October as compared to other months. The CSDG also demonstrates that some individuals experienced significantly increased numbers of asthma exacerbations at certain times of the year unique to themselves. Because the CSDG predicts exacerbations, it was shown to be applicable to prevent such exacerbations by prophylactic increase in CS dose during a high-risk season for selected CS-dependent asthmatics.


Plasma histamine changes during provoked bronchospasm in asthmatic patients. Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.


Histologic studies of human skin test responses to ragweed and compound 48/80. III. Effects of alternate-day steroid therapy. Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day ("day on") and day 8 ("day off") of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.


Canine airway responses to acetylcholine, prostaglandin F2alpha, histamine, and serotonin after chronic antigen exposure. Dose-response curves were obtained for aerosols of acetylcholine (ACh), prostaglandin F2alpha (PGF2alpha), histamine (H), and 5-hydroxytryptamine (5-HT) on pulmonary resistance (Rp) and dynamic lung compliance (Cdyn) in Ascaris-hypersensitive dogs. Previously, these animals had been subjected to chronic biweekly "allergic asthmatic" episodes by aerosol administration of Ascaris antigen. When examined either one week before or after antigen provocation the airways were not hyperreactive to ACh, H, or 5-HT but did demonstrate a modest hyperreactivity to PGF2alpha. When aerosol dose-response curves were obtained for these agonists immediately following an "allergic asthmatic" episode, the airways were hyporeactive to PGF2alpha, H, and 5-HT, but not to ACh. Studies with atropine indicated that the hyporeactivity was the result of decreased airway responsiveness to both direct and indirect effect of PGF2alpha and H. It is concluded that, in dogs, chronic antigen challenge is not accompanied by a general increase in airway reactivity to pharmacologic agents.


Circulating basophils in normal subjects and in subjects with hay fever. The relationship of hay fever symptoms and changes in the number of circulating basophils was studied in 12 subjects clinically sensitive only to ragweed and in 10 nonatopic subjects before, during, and after the ragweed season. Total white blood counts, absolute basophil counts, and symptom scores were recorded twice weekly from mid-June through October, 1974, and compared with the ragweed pollen count. The results indicated that the absolute and relative number of basophils were significantly elevated (p less than 0.001) in the hay fever group when symptoms occurred. As the symptom score of the allergic group increased during the ragweed season, the number of basophils also increased, only to decrease to control values when symptoms subsided. The basophil counts of the atopic group were significantly higher than those of the nonatopic group during the control periods. The nonatopic group also showed a significant elevation of basophils during the ragweed season, but to a much lesser extent than the atopic group. It is concluded that: (1) subjects with symptomatic hay fever have a significantly elevated absolute and relative basophil count which correlates with the exacerbation and remission of symptoms; (2) nonatopic subjects also have a small but significant elevation of basophils during the ragweed season; and (3) the elevation of basophils in the atopic group during symptoms is significantly greater than in the nonatopic group during the ragweed season.


A comparison of the beta-blocking activities of practolol, sotalol, and propranolol in human and guinea pig tracheal smooth muscle. Beta adrenergic blockade was studied in vitro with human tracheal muscle strips and guinea pig tracheal chains. It was shown in isolated smooth muscle from both man and guinea pig that the order of potency for the three beta-blocking agents studied was: propranolol greater than sotalol greater than practolol. Under the conditions of this study, propranolol was about 30,000 times and sotalol about 30 times as potent as practolol. The order of potency suggests that the nature of adrenergic blockade induced by practolol on tracheal smooth muscle is only weakly beta2-relative to the blocking effects of propranolol and sotalol. Beta adrenergic blockade by propranolol, sotalol, and practolol produced different degrees of increased histamine lethality in mice. Whereas both propranolol at 0.01 mg/kg and sotalol at 1.0 mg/kg resulted in 100% histamine-induced lethality, practolol at 50 mg/kg resulted in only 50% histamine-induced lethality. These data, when added to those from our previous studies, suggest that the mechanisms responsible for resistance to the effects of histamine in untreated mice are at least partially mediated by the beta2-adrenergic system. Thus, in three different tissues, the blocking activity of practolol was shown to be less than that of sotalol or propranolol.


Competency-based education.

Competency-based education. The essential elements of a P/CBDE program include the delineation of role-derived dietetic competencies, which are publicly stated in behavioral terms. The criteria used to measure the accomplishment of these competencies are criterion-referenced, and the student acquires the competencies at his own rate. Much confusion exists in differentiating between the essential characteristics and implementation modes. The use of modern technology and modular packaging of learning experiences does not automatically lead to a P/CBDE program. These are merely tools. The clear identification of competencies, objectives, and performance criteria are the essence of P/CBDE. Currently, dietetic educators are formulating competencies for their own programs. A national group of "experts" will need to be convened to develop competencies for the profession as a whole.


Longitudinal studies of food intake and weight of women from ages 18 to 56 years. One hundred fifty-eight women have been studied over a thirty-seven-year period, starting with personal contacts during college and continuing by intermittent mail questionnaires through 1973. Food intakes were calculated from 24-hr. dietary recalls at each sampling. The dietary adjustments in calories and ten nutrients which were made during thirty-seven years were presented. Changes in weight are discussed in relation to dietary changes.


Zinc in selected hospital diets. Comparison of analysis vs. calculation. Sample hospital meals for breakfast and the noon and evening meals for regular, ovo-lacto-vegetarian, and renal diets were collected for seven consecutive days. The daily zinc content of each diet was determined, using atomic absorption spectrophotometric analysis and by calculation, using the USDA provisional tables on the zinc content of individual foods. The data indicated that the provisional tables provide a reasonable estimation of zinc content of regular or renal diets with errors approximately 10%. However, a 35% overestimation occurred for vegetarian diets. A major cause of error between assayed and calculated values was probably due to substituting items not included in the tables. The mean zinc content for the regular diet, as offered, was 97% of the adult recommended allowance for zinc, while the vegetarian diet provided 81% of the allowance. The average renal diet contained 49% of the allowance. Certain types of vegetarian and low-protein diets may be inadequate in total and/or available zinc. Also important in evaluating hospital diets for adequacy of zinc are the actual intake and the condition of the patient.


Effects of storage and handling on vitamins in fresh lima beans. Fresh Lima beans were subjected to various combinations of handling factors, including storage time and temperature, air during storage, water during preparation, hulling, and preparation method, to determine their effects on ascorbic acid, thiamin, and carotene content. Freezing resulted in highly significant losses of ascorbic acid and thiamin. Longer storage time and higher storage temperature resulted in significant reduction in ascorbic acid. Bruising, such as that occurring when beans are mechanically hulled, caused significant losses of both carotene and ascorbic acid. Significant interactions indicated that subjecting beans to circulating air and to bruising increased degradation of ascorbic acid and carotene. Increasing storage temperature compounded the effects of air circulation and of storage time on ascorbic acid. For example, 24-hr. storage at 45 degrees F was as severe as 72 hr. at 37 degrees F. Highest overall content of ascorbic acid was attained with hand-hulled samples stored in still air before cooking. Lowest content of ascorbic acid occurred in bruised beans cooked in copper-fortified water.


Group approach to weight control: behavior modification, nutrition, and health education. We have had a positive experience using a modified approach to behavior modification of eating patterns, exercise, and activity, along with nutrition and health education. During the first year, forty-four adult patients completed the program, which was conducted in the out-patient clinic of a large hospital by a dietitian and a nurse practitioner. A cross-section of the patient population was admitted. The program had a pre-determined number of sessions, each of which was partially structured. When compared with the patients in individual therapy in our Nutrition Clinic, a more consistent weight loss in a shorter time was observed in the group participants. Whether the techniques described here will lead to sustained weight loss over time bears further study.


Reaction time as a diagnostic measure in senility. Both simple and disjunctive reaction times (RT) are known to slow with aging but there is a paucity of information on RT changes in senility. Since disjunctive RT involves cognition in addition to the sensory-motor speed and attentional components of simple RT, it was hypothesized that disjunctive RT would be a reliable index of age-related mental decline. To test this prediction, simple and disjunctive RT were measured in matched groups of 20 normal and 20 cognitively impaired elderly. Simple RT was slower in the senile patients than in the normal subjects, but this difference was accounted for by differences in disjunctive RT. The senile patients showed a much larger performance decrement with respect to disjunctive RT than did the normal subjects--a difference which was not accounted for by differences in simple RT. In a discriminant function analysis, disjunctive RT alone correctly identified the senile patients and the normal subjects with 86% accuracy. Thus, this measure proved to be a reliable index of age-related mental decline. Preliminary data indicate that disjunctive RT slowing is correlated with non-memory mental decline, and that poor performance is related to the need for care and supervision.


Potassium, glucose and insulin administration in acute myocardial infarction: a five-year study. Two hundred and twelve patients with acute myocardial infarction were treated for 14 days with daily doses of potassium (3 gm orally), glucose (280 gm orally) and regular insulin (16 units subcutaneously), all given in 4 fractional doses. The incidences of arrhythmias, heart failure and systolic blood pressure below 70 mm Hg, as well as the mortality rate, were compared with those for another group of 600 myocardial infarction patients who were not given this treatment. Though there was some reduction in the incidence of cardiac arrhythmias, it was not statistically significant. However, there was a strikingly significant decrease in the incidences of heart failure and blood pressure below 70 mm, as well as in the early mortality rate. Our findings should encourage the continued use of potassium, glucose and insulin therapy in acute myocardial infarction.


A low-vision clinic at a home for the aged. The objective of a low-vision clinic developed at the Jewish Home and Hospital for Aged was to improve the visual capabilities of the residents who were not helped by the regular eye clinics. Eighty-three patients (72 women, 11 men) were examined the first year. Ages ranged from 71 to 101 years. The causes of poor vision were mainly senile macular degeneration, cataract formation, chronic glaucoma, severe myopia, aphakia, and combinations of these diseases. Vision ranged from 10/50 at 10 feet (20/100 at 20 feet) in the better eye, to only the ability to distinguish hand movements or to perceive light. With the use of visual aids such as distance or reading glasses and various forms of magnifying glasses, some improvement occurred in 61 of the 83 patients. The follow-up examination was within one year in most cases. It was concluded that in order to examine and treat such patients properly, much more time and patience were required than is usually possible in a regular eye clinic. This involved the help of more social workers and volunteer assistants. Nevertheless, the results were worthwhile for this type of patient.


Therapeutic group process with the institutional elderly. This paper reviews the status of geriatric group psychotherapy and the experience with such programs at the Miami Jewish Home and Hospital for the Aged. Specific ways are suggested for enhancing the administration of group psycho-therapy programs in the geriatric institutional setting. Group therapy techniques adapted to the specialized needs of the aged are of definite therapeutic benefit.


Iron deficiency anemia in postmenopausal women. In 90 postmenopausal women aged 55 or older residing in health care facilities, a survey was made of hemoglobin levels and food habits that reflected their consumption of iron-rich foods. The reasons for inadequate dietary intakes of iron are discussed. There is need for better understanding of iron metabolism. Recommendations are made for the prevention of iron deficiency anemia in postmenopausal women and for achievement of the highest possible level of health as affected by the intake of iron and related nutritional factors.


[Toxoplasmosis and pregnancy. Evaluation of 2 years of prevention of congenital toxoplasmosis in the maternity ward of Hôpital Saint-Antoine (1973-1974)]. The authors report the results of prophylaxis of congenital toxoplasmosis in a maternity hospital in Paris for a two years period (1973-1974). 6269 pregnant women were surveyed. 18 toxoplasmosis were detected in evolution at the first prenatal examination, 10 seroconversions were identified among the first examination antibody negative women, when re-examined during the pregnancy. 25 of these 28 women were treated regularly. The seroconversions of the 3 other women were detected only at delivery. In addition 25 women were treated because of high antibody titers (Dye-Test greater than or equal to 300. U.I/ml). 6 congenital toxoplasmosis, 2 of them were manifest, were observed among the children whose mothers were treated for confirmed toxoplasmosis. The extremely low level of seroconversions may be in relation to hygienic and dietetic prescriptions. The difficulties of this prophylaxis are analysed: they are due to studied population and to problems of interpretation or serologic examinations.


Experimentally induced Haemonchus contortus infections in the rabbit. Haemonchus contortus originally derived from an Ontario field strain was used to infect laboratory rabbits. Both enshealthed and artificially exsheathed larvae were given at doses of up to 10 million larvae per rabbit. Only artifically exsheathed larvae were infective and a dose of at least 50,000 was required to produce a significant level of infection. H. contortus completed its development in the rabbit, but at a slower rate than in the sheep. Although a few fecund females were found 35 days after infection no eggs were observed on faecal examination. A high proportion of early fourth stage larvae were recovered from numerous rabbits including some which were examined well beyond a postinfection period when all worms should have been in the adult stage. This phenomenon occurred when freshly harvested and exsheathed larvae were used. Post-exsheathed cold conditioning of larvae at 5degreesC further increased the proportion of early fourth stage larvae (maximum proportions were found after 21 and again after 79 days of cold conditioning and thereafter declined). Whether such larvae were inhibited cannot be stated definitely. However, several of these larvae contained crystalline rods within their soma, and the structure of the crystals was similar to those previously described from inhibited H. contortus larvae recovered from sheep. It was concluded that the laboratory rabbit could be a useful host for further studies on some aspects of the biology and pathogenicity of H. contortus.


Laboratory infections of Scheloribates spp. (oribatid mites) with Moniezia expansa and M. benedeni. Scheloribates laevigatus (Koch, 1836) and Scheloribates fimbriatus (Thor, 1930), predominant species of oribatids in soil of Bombay region, were experimentally exposed to infection by uniform suspensions of eggs of Moniezia expansa and M. benedeni. The percentages of mites infected and the average number of cysticercoids developing were observed in 12 sets of experiments. The mites were more readily infected with eggs of M. expansa than with those of M. benedeni. S. laevigatus were infected with M. expansa and less with M. benedeni than S. fimbriatus.


Neodiplostomum (Conodiplostomum) ramachandrani sp. n. from Mueller's rat, Rattus muelleri in Malaysia. Neodiplostomum (Conodiplostomum) ramachandrani sp. n. is described from Rattus muelleri in Kepong, Selangor, Malaysia. It is characterised by having symmetrical dumbell-shaped testes, and vitellaria as a single ventral band in the hindbody. The taxonomic relations of Neodiplostomum, Conodiplostomum and Fibricola are discussed and possible significance of the fluke as an ecological indicator noted.


The distribution of Nematospiroides dubius within the small intestine of laboratory mice. Analyses of primary infections of Nematospiroides dubius in male and female laboratory mice show that on days 4--6 post-infection worms occupy up to 50% of the small intestine but as the age of the infection increases worm populations are highly aggregated in relation to the anterior sections of the small intestine. Individual worms are also shown to be aggregated with respect to each other. Between days 42 and 60 post-infection, although the pattern of distribution of N. dubius along the small intestine does not significantly change, survival of worms is influenced by both age and sex of ASH/CSI S.P.F. mice, reasons for which are discussed in the light of previous work on primary infections of N. dubius in other strains of laboratory mice.


Haplorchoides Chen, 1949 (Haplorchinae: Heterophyidae) in freshwater fishes. Two metacercariae of Haplorchoides, recorded in the fingerlings of over a dozen species of freshwater fishes, are described and illustrated. Ovigerous flukes were recovered from older specimens of two species of fishes procured from the same locality. Comparison of taxonomic characters of the juveniles and adults suggests that they are conspecific. The metacercariae and adults are assigned to two new species, Haplorchoides pearsoni and H. Mehrai. The observations, presented herein, necessitated a review of the species named under this genus and a revision of the generic diagnosis. The reports on fish intermediaries of H. attenatus have been enlarged.


A study of the relationship between temperature and the infectivity of Schistosoma mansoni and Schistosoma haematobium cercariae. It was shown that maintenance of cercariae of S. mansoni and S. haematobium at low (10degreesC) and high temperatures (40degreesC) markedly increased their mortality during penetration of mammalian host skin. These increased losses in the skin accounted for the known decrease in infectivity, as measured by adult worm recovery, of cercariae kept at low or high temperatures.


The prevalence, relative abundance and site distribution of nematodes of the subfamily Cyathostominae in horses killed in Britain. A total of 21 species of Cyathostominae was found in the lumen of the large intestine of 86 mature horses of various ages and breeds killed in south-west England during 1972-1974. Cylicostephanus longibursatus, C. goldi, C. calicatus, Cyathostomum catinatum, C. coronatum and Cylicocyclus nassatus were found in over 80% of the horses, while 12 of the remaining species were detected in less than 30%. Quantitative studies on 55 horses showed the adult cyathostome burdens to rise to a sharp peak (average over 400,000/horse) in April-June and a lower one in November-December. Parallel fluctuations occurred in the lumen populations of 4th-stage larvae. The most numberous cyathostomes were generally those species with the highest prevalence. The five most plentiful (C. nassatus, Cyathostomum catinatum, Cylicostephanus longibursatus, C. minutus and C. goldi) comprised over 90% of the total number of adult cyathostomes recovered. The three regions of the large intestine had adult cyathostome faunas of different composition. That of the dorsal colon was dominated by C. longibursatus and C. goldi, the ventral colon by Cylicocyclus nassatus and Cyathostomum catinatum, while the sparsely inhabited caecum accommodated several equally numerous species. Each species showed a characteristic site distribution, 11 occurring predominantly in the ventral colon, eight in the dorsal colon and two in the caecum. Seasonal changes in the site distributions of C. catinatum and Cyclicocyclus nassatus and in the size of the cyathostome burdens are discussed in relation to the epidemiology of cyathostome infections.


Mouse factor B of the alternative pathway of complement activation. I. Purification, characterization, and functional behavior. Mouse factor B was purified and a monospecific antiserum was raised. The physicochemical data of this protein (108,000 m.w., 5.9 S, 5.9 to 6.05 isoelectric point) were determined. The functional behavior resembles that of human and guinea pig factor B and it operates efficiently in the C3 feedback cycle of the alternative pathway of complement activation. A provisional scheme is given for the operation of the C3bB enzyme on the cellular (macrophage) level.


Complement receptor lymphocytes in the rabbit I. an SIg-negative subpopulation in the appendix. Complement receptor lymphocytes (CRL) were detected in various rabbit lymphoid tissues by the ability of these CRL to form rosettes with sheep red blood cells coated sequentially with rabbit antiserum directed against sheep red blood cell stroma and horse serum as a nonhemolytic source of complement (EAC). The rosette assay was shown to be specific for complement receptor (CR) activity and the EAC capable of detecting both C3b and C3d specific receptors. With lymphocyte preparations containing less than 5% phagocytic cells, the average per cent CRL in the various tissues studied was as follows: thymus 1%, popliteal lymph node 18%, spleen 30%, appendix 35%, and peripheral blood 45%. Double assays in which the lymphocytes were prestained with an FITC-labeled Fab fragment of a goat anti-rabbit Fab antibody before rosetting indicated that CRL were a subpopulation of surface immunoglobulin (SIg)-bearing lymphocytes in popliteal lymph node, spleen, and peripheral blood. In the appendix, however, in addition to finding SIg+ CR+ and SIg+ CR- populations, an SIg- CR+ population was consistently found. Double assays employing FITC-labeled goat antibodies specific for mu, alpha, and gamma determinants were also performed to determine if there was any relationship between the class of Ig displayed and presence of CR. It appeared that an approximately equivalent percentage of both IgM- and IgG-bearing cells also displayed CR. Experiments in which appendix cells were treated with Pronase to remove SIg and CR and the cells cultured in vitro to allow regeneration of surface markers confirmed the existence of SIg+CR+, SIg+CR-, and SIg-CR+ lymphocyte subpopulations. Whether the SIg-CR+, population represents a developing B cell population which will eventually also express SIg or whether it belongs to the T or "null" cell populations is unclear at present.


Activation of the alternative pathway of the complement system by radiographic contrast media. Nine patients who underwent radiographic contrast media (RCM) infusion for diagnostic purposes were studied. Simultaneously, venous blood samples were collected and complement was measured. None of the patients had a clinical history of allergy to previous infusion of RCM. A significant drop in plasma complement (CH50) levels was detected in five of nine patients. The drop in CH50 was observed within the first 20 min after the initiation of RCM infusion. All five patients in whom a drop in complement was found showed a decrease in hemolytic C3, properdin, and factor B. In addition, by radial immunodiffusion low levels of C3, C6, properdin, and factor B were observed and split products of C3 and factor B were identified by immunoelectrophoresis. No significant changes in C1q and C4 were detected by radial immunodiffusion during the study of these five patients. This study strongly suggested that in some patients undergoing RCM infusion, activation of the complement system occurred and this activation appears to be through the alternative pathway.


Analysis of murine oncofetal antigens as tumor-associated transplantation antigens. In previous studies with in vitro activated cytotoxic T lymphocytes, we have demonstrated the presence of oncofetal antigens (OFA) on a range of murine tumor cells. The present studies with the same tumor lines attempt to determine whether these antigens are also capable of activating lymphocyte responses in vivo. Several experimental designs were followed, each being performed many times (1). Preimmunization of mice with irradiated fetal liver cells and followed by challenge with viable tumor cells did not consistently produce a state of tumor resistance. However, injection of live fetal cells frequently led to enhanced tumor growth (2). The growth of tumors in multiparous mice can be inhibited, in contrast to controls, but this effect was relatively short lived after parturition (3). Preimmunization with fetal cells in vivo did not result in augmented secondary cytotoxic T cell responses in vitro (4). Immunization of mice with irradiated tumor cells frequently led to a state of resistance to the clonal growth of hemopoietic fetal cells, although again the level of resistance was usually relatively weak. From the overall results, we conclude that OFA are relatively poor immunogens on tumor cells or fetal cells in vivo, and in contrast to in vitro responses, do not act as potent tumor transplantation antigens.


Complement-induced ultrastructural membrane lesions: requirement for terminal components. The step in the complement (C) sequence at which 8- to 11-nm ring-shaped lesions are formed on antibody-coated erythrocytes (EA) has remained controversial. Some workers have concluded that these lesions appear at the C5 step and are not ultrastructural correlates of lysis; others hold that these lesions are formed only after the action of C8 and C9 in association with lysis. We have re-examined this problem by using sheep EA and human sera genetically lacking C5, C6, C7, or C8. Electron micrographs of negatively stained membranes (x 220,000) were read in blind fashion and the results correlated with 125I-C5 binding. Rare structures resemblind C-induced ring lesions were found on EA exposed to C5-deficient (C5D), C6D, C7D and C8D sera or to heated normal serum, with no significant differences among these sera (lesion density 0 to 0.26/mum2). Fresh normal serum (NHS) produced 140 to 220 ring lesions/mum2. C5 binding to EA in C8D serum was 60% of that observed in an NHS control; in C6D and C7D sera C5 binding was 4 to 11% of the normal value. Iodine treatment of sera (to enhance C5 uptake by C2 oxidation) increased C5 binding in C6D serum to 40 to 65% of that seen in native NHS; in iodine-treated C7D and C8D sera C5 binding was 250 and 440%, respectively, of the native NHS value. No increase in ring lesions was observed, however, except in the iodine-treated NHS. Thus, in whole serum, C5 binding is not sufficient to produce ultrastructural membrane rings in the absence of later-acting C components, at least through C8. The formation of ring lesions appears to have C requirements similar to those necessary for lysis.


Prearmed effector cells and the target cell specificity of lectin-induced cellular cytotoxicity. We have investigated mechanisms by which plant lectins induce human peripheral blood mononuclear cells to kill red blood cells (RBC) from different species selectively. Cytotoxicity was induced by both mitogenic components of phytohemagglutinin-P (PHA), erythroagglutinating (E-PHA) and leukoagglutinating (L-PHA), and the nonmitogenic lectin wheat germ agglutinin (WGA). The target cells used in an overnight chromium release assay included human autologous RBC, human allogeneic RBC, and xenogeneic RBC from sheep or chickens. Although E-PHA induced cytotoxicity for all cell types, L-PHA caused human mononuclear cells to kill only xenogeneic RBC and, conversely, WGA induced killing of only human RBC. These differences allowed further investigation of possible control mechanisms. The target cell specificity associated with lectin-induced cellular cytotoxicity did not correlate with lectin binding to, or agglutination of, the different red blood cell types. Furthermore, preincubation of RBC with lectins followed by washing did not result in cytotoxicity. However, when the mononuclear cells were preincubated with the lectins, the same cytotoxic specificity was observed as when lectins were present during the entire assay. These experiments suggest that the target cell specificity observed with lectin-induced cellular cytotoxicity is related to a prearmed lymphocyte which seeks out and kills the appropriate target cell.


Immunopathogenesis of autoimmune tubulointerstitial nephritis. II. Role of an immune response gene linked to the major histocompatibility complex. Immunization of strain XIII guinea pigs with rabbit renal tubular basement membranes (TBM) in CFA consistently results in severe autoimmune tubulointerstitial nephritis (TN). Strain II guinea pigs similarly immunized do not develop this disease. F1 guinea pigs were found to be intermediate between inbred strain II and XIII animals with regard to extent of autoimmune TN and anti-TBM antibody production. The F1 X II backcrosses segregated into two groups with regard to antibody production and disease extent. Those backcrosses tissue typed as II+, XIII+ were similar to the F1 guinea pigs. Those backcrosses typed as II+,II+ demonstrated little disease and low anti-TBM titers similar to the inbred strain II animals. F1 X XIII backcrossed guinea pigs segregated into II+,XIII+ or XIII+,XIII+ subgroups on the basis of lymph node typing. The II+, XIII+ backcross animals resembled F1 guinea pigs with respect to anti-TBM response and disease extent; whereas the XIII+, XIII+ backcrosses developed severe disease and high anti-TBM titers as observed in the inbred strain XIII animals. These experiments suggest that susceptibility to autoimmune TN in the guinea pig is linked to the strain XIII major histocompatibility complex and that an immune response gene governing this susceptibility may be inherited as a single dominant or co-dominant trait.


Association of histocompatibility haplotype HLA-A3-B7 with multiple sclerosis. Tissue typing was performed on 1000 unrelated multiple sclerosis (MS) patients and 1000 unrelated healthy controls. In addition, segregation analysis of HLA antigens and haplotypes in 36 MS families was done. The following results were observed: HLA-A3 and HLA-B7 were found significantly more often in MS individuals; haplotype HLA-A3-B7 was observed significantly more often in MS patients than in healthy indiciduals of the same population; the association between HLA-A3 and HLA-B7 was signigicantly stronger in MS patients than in controls; the haplotype HLA-A3-B7 shows a common segregation with the disease multiple sclerosis (p = 0.02); and the hypothetical "MS-disease-susceptibility-gene" may be located between the second locus and the HLA region and the MLC (mixed lymphocyte culture)-histocompatibility-determinant-region on chromosome No. 6.


Reduction of the in vitro cytotoxic lymphocyte response produced by in vivo exposure to semiallogeneic cells: recruitment or active suppression? Twenty-four hours after intravenous injection of (C57BL/6 X DBA/2)F1 hygrid lymphoid cells into C57BL/6 mice, the in vitro cytotoxic lymphocyte (CL) response of the C57BL/6 spleen and LN cells against DBA/2 alloantigens can be greatly reduced. The reduction is specific for the foreign alloantigens injected; is reduced by irradiating the cells before injection; develops significantly within 10 min of injection, thereafter increasing with a time constant of about 2 hr; varies with the number and origin of cells injected; can be induced byseveral subpopulations of injected cells within one tissue; varies with the host organ tested (e.g., injection of 10(4) semiallogeneic LN cells can reduce hose LN response more than 100-fold and have no effect on host spleen); and (for the LN response) is largely reversed by treatment with anti-H-2 antibody plus complement specific for the injected cells. The reduction appears to be induced by grafted cells entering host lymphoid organs rather than, e.g., host cells being specifically recruited to go elsewhere. When cocultured with normal cells, lymphoid cells from mice injected as above do not reduce the in vitro CL response of the normal cells but do if left in vivo for 7 days before testing. If left 1 day in vivo, followed by 4 days culture in vitro with the same alloantigen, they strongly reduce the normal cell response. The reduction is increased by both the in vivo and in vitro exposure. The grafted cells, once in the host lymphoid tissue, appear to activate a host suppressor mechanism which develops in vitro and reduces the CL response.


Response of human lymphocytes to PHA and Con A, dependent on and regulated by THF, a thymic hormone. The response of human lymphocytes to T lectins was shown to be dependent on and regulated by THF (thymus humoral factor). When human lymphocytes were stimulated with T lectins in the presence of dialyzed human plasma (DHP) which probably contains a low thymic hormone concentration, we observed a reduced response to PHA and Con A, compared to that observed in the presence of whole human plasma (WHP). This reduced reactivity to T lectins in the presence of DHP was restored by the addition of plasma dialyzates or THF. On the contrary, addition of THF to cultures in the presence of WHP caused a significant reduction in reactivity to T lectins, suggesting that enhancement or reduction of the response of human lymphocytes to T lectins by THF depends on the endogenous content of the thymic hormone in the plasma. From the present data it is suggested that the response of human cells to PHA behaves differently from that to Con A, as reflected in their dependence on THF. Although the response of human cells to Con A is increased by THF only in the presence of DHP, the response to PHA is also enhanced by THF in the presence of low WHP concentrations of even in the absence of WHP.