[Variability of neuronal activity of the parastriate cortex before and after callosotomy]. In acute experiments on anesthetized cats, variability of the unit activity in the field 18 of the visual cortex was studied.  Both the spontaneous activity and the evoked activity by series of different light stimuli, were analysed.  The data obtained show that callosotomy does not affect the variability of the spontaneous unit activity in the parastriate cortex.  However, it does decrease the variability of the unit activity qualitative response (excitation--inhibition) to stimulation.  The callosotomy increases variability of the predominant input (either ipsi--or contralateral) in regard to the mean spontaneous activity prior to and after a series of stimuli and decreases it in regard to the mean spontaneous unit activity for the whole period of study.


[Some peculiarities of neuron reaction in the upper and lower layer of the striate cortex]. Responses of 440 neurons in the albino rat visual cortex to flash were studied. The number of neurons with excitatory responses predominated in upper layers. Analysis of time parameters of secondary activation of the excitatory responses revealed 5 excitatory types of neuronal response. The excitatory responses of different types had an irregular distribution over layers with corresponding differences in change of information indices and response variability during primary activation. Moreover, information indices of neuronal responses in upper and lower layers changed unequally.


[Relation of excitability cycles of cortical reactions to the qualities of afferent stimuli]. The excitability cycles of neurons of the rabbit visual cortex in response to the optic nerve shock were compared with those in response to small light flashes.  The pairs of stimuli consisted either of conditioned shock and testing light flash or of conditioned light flash and testing shock.  The inhibitory phase of the response to the nerve shock was unable to depress a powerful reaction to adequate light stimulation.  However, the profound inhibition of response to the optic nerve shock was obtained at the end of the response to the preceding light stimulation.


UBioelectric activity of the brain of cats in wakefulness and various sleep stages in cats. Multiple recording of biopotentials with implanted electrodes from the globus pallidus, caudate nucleus, putamen, ventro-lateral thalamus, thalamic center median, midbrain reticular formation, and the posterior hypothalamus, was carried out.  Peculiar features were noted during slow-wave sleep in the activating RF.  However, disappearance of these features during transition to fast sleep and persisting slow potentials in some structures at that suggest the hypnogenic system to be rather complicated in its spatial-temporal structure and not to be associated with just a single "leading" structure as, for example, the RF.


Growth hormone kinetics in diabetic patients. Several reports have shown that average plasma GH concentrations in insulin-treated and in juvenile diabetics are elevated in respect to normal values: these findings have been alternatively attributed to an increased pituitary GH secretion or to a lower GH catabolism induced by the disease. To reinvestigate the problem we studied GH kinetics in twenty-four diabetics using 125-I-GH. The patients were all normal in body weight and their fasting blood sugar did not exceed 190 mg. per 100 ml.; fourteen normal subjects were included as a control group. After single injection of the tracer, the plasma disappearance curve of labeled hormone was obtained. Starting from this curve, metabolic clearance rate (MCR), fractional catabolic rate (FCR), initial distribution volume (IDV), and total distribution volume (TDV) were computed; MCR and plasma concentration of endogenous GH in plasma samples were used to estimate the amount of hormone irreversibly lost during the experiment (IHL240). The major points that result from the comparison of the values obtained in diabetic patients with those in the normal group are: MCR values in diabetics do not differ from those found in normals (63.6 plus or minus 19.6 and 64.6 plus or minus 24.3 ml./min./m.-2 respectively). The higher plasma concentrations of endogenous GH in diabetics together with a normal MCR, yield hormone loss values (IHL240) significantly larger than normal (46.4 plus or minus 29.5 mug/240 min. as compared to 23.7 plus or minus 24.5) thus indicating that an increased GH secretion is present in diabetics. TDV, fairly constant in normals, (5.8 plus or minus 0.9 L./ml-2) tends to decrease in diagetic patients as the disease progesses; in fact the values of TDV are significantly reduced (P less than 0.005) in long-term diabetics (greater than 10 yrs. of disease) while TDV of short-term diabetics (less than 10 yrs.) does not differ from the normal value (4.6 plus or minus 1.16 L./m.-2  and 5.8 plus or minus 0.9 L./m.-2, respectively).


Studies on the nature and mode of action of the insulin-sensitive glucoregulator receptor in the central nervous system. In vivo studies were undertaken in rats to provide evidence of the neural nature, tentative localization and mode of excitation of the insulin-sensitive central nervous system (CSN) glucoregulator center. In rats under light barbiturate anesthesia minute amounts of insulin injected into the carotid artery resulted in an immediate decrease of the systemic blood sugar. This hypoglycemic action of regional insulinzation of the CSN was lost when the animals were subjected to prolonged, deep barbiturate narcosis. Competitive inhibition of glucose utilization in the CSN region by intracarotid administration of 2-deoxy-D-glucose did not block the systemic hypoglycemic effect of subsequent intracarotid insulin injection. Chronic endogenous hyperinsulinemia produced by daily growth hormone treatment resulted in an insensitivity of the CNS glucoregulator center to exogenous insulin. The ratio of the quantity of the injected insulin and the pre-existent plasma insulin concentration showed direct correlation with the systemic hypoglycemic response that followed intracarotid injection. Present data support the hypothesis that the insulin-sensitive glucoregulator center located in the area supplied by the carotid artery is neural in nature, because of its inhibition by barbiturate anesthesia. The data are compatable with the working hypothesis that the center is located in the hypothalamus, since light cortical barbiturate anesthesia did not, but deep anesthesia did have an inhibitory effect on it. Marked interference by chronic hyperinsulinemia suggests that the receptor center estimates the metabolic status of the animal through means related to physicochemical binding of insulin to specific receptors. However, since our attempt to inhibit glucose utilization in the CNS was without effect on the activity of the center, it appears that the singal for the glucoregulatory impulse is not insulin facilitation of glucose utilization in the receptor area, but another parameter of insulin action.


Dynamics of tolbutamide, glucose, and insulin interrelationships following varying doses of intravenous tolbutamide in normal subjects. Four healthy adult subjects received intravenous tolbutamide (TOL) at six different doses (twenty-four tests): 0.0625 gm., 0.125 gm., 0.25 gm., 0.5 gm., 1.0 gm. and 1.5 gm. Blood glucose (BG), serum immunoreacctive insulin (IRI) and serum TOL levels were determined before and for 180 minutes after TOL. There was a highly significant correlation of the dose of TOL with the peak IRI (p less than .01), zero to ten minute IRI area (p less than .001), and zero to sixty minute IRI area (p less than .001) and with the decline in BG expressed as zero to sixty minute BG area (p less than .001). Similar significant correlations were observed between levels of TOL and both IRI and BG. At each dose level the IRI response correlated significantly with the BG fall. An additional eighteen subjects received the 1.0 gm. dose. In these, serum TOL levels did not correlate with either BG or IRI. These subjects also received intravenous glucose (0.5 gm. per kilogram body weight). BG levels did not correlate with IRI. However, there were striking correlations between TOL and glucose-stimulated peak IRI (p less than .001), zero to ten minute IRI area (p less than .05). The mean (plus or minus SEM) space of distribution for glucose (G.S.) and tolbutamide (TLS.) was found to be 13.45 plus or minus 0.71 and 6.34 plus or minus 0.31 L., respectively. There was a significant dose-response relationship exists between TOL and IRI. TOL- and glucose-induced IRI secretion dynamics suggest strong similarities between mechanisms of rapid IRI release and/or size of available IRI storage pools.


Hyperinsulinemia and hypoinsulinemai. Insulin responses to oral carbohydrate over a wide spectrum of glucose tolerance. Oral glucose tolerance tests using a 75 gm. carbohydrate load were performed on 396 Pima Indians. Subjects were divided into groups on the basis of two-hour plasma glucose levels and the patterns of insulin response examined. Two-hour insulin levels were highest in the group with two-hour plasma glucose levels between 140-169 mg,/100 ml. and then fell progressively until levels about 400 mg./100 ml. were reached. Half and one-hour insulin levels showed little change in the groups with two-hour glucose levels up to 170 mg,/100 ml., but at higher glucose levels these insulin levels also progressively diminished. Fasting insulin levels were relatively unchanged over the entire range of glucose inintolerance. Obesity was the most important factor influencing the fasting insulin levels. Glucose level was the major determinant of post-load insulin responses, but these were also significantly influenced by obesity. No effect of age or sex on insulin levels was demonstrated. Comparison with other published data indicated that different interpretations of insulin response in subjects with "mild diabetes" have resulted from comparisons of groups with different degrees of glucose tolerance.


Differential effects of alpha- and beta-D- glucose on insulin and glucagon secretion from the isolated perfused rat pancreas. The efficacy of alpha and beta-D-glucose in causing insulin release and suppressing glucagon release from the isolated perfused rat pancreas was tested. In order to allow simultaneous assessment of glucose effect on both alpha and beta-cells, the pancreas was continually perfused with a physiological amino acid mixture (10 mM) which provokes glucagon secretion and also stimulates the beta-cells, provided glucose is present. Under these conditions the alpha-anomer of D-glucose at 3 and 6 mM proved significantly more potent than the beta-anomer in inducing insulin release and in inhibiting glucagon secretion. These data lend further support to the concept that alpha-cells and beta-cells contain glucoreceptors controlling glucagon and insulin seckretion and show that certain physiochemical properties of these receptors are alike in both types of cells.


Dylexia in children and young adults: three independent neuropsychological syndromes. In an attempt to delineate causal factors in dyslexia, 113 children and young adults (age-range eight to 18 years) were divided into three groups: those with brain damage who could read (n=31), those with brain damage who were dyslexic (n=53), and those without brain damage who were dyslexic (n=29).  A battery of neuropsychological tests was presented to each participant.  No significant differences were found between the two dyslexic groups.  Three syndromes--language disorder, articulation and graphomotor dysco-ordination, and visuo-perceptual disorder--were found among the great majority of those with dyslexia.  The results support a model of dyslexia as being caused by multiple independent defects in higher cortical functioning, as opposed to the theory of a single causal defect.  A clinical description of each syndrome is given and models of dyslexia are discussed.  The authors stress the desirability of including brain-damaged readers as a control group in any future study on causal factors in dyslexia.


The Stycar language test.

The Stycar language test. The principles and practical application of the STYCAR Developmental Language Test are briefly described.  The test, which is one of the STYCAR series (Sheridan Tests for Young Children and Retardates, Sheridan 1973), consists of three widely overlapping testing procedures i.e. the Common Objects Test (one to two years), the Miniature Toys Test (21 months to 4 1/2 years) and the Picture-book Test (2 1/2 to seven years).  The picture-book includes lists of speech sounds, words and sentences for recognition and repetition, to detect and define difficulties of auditory discrimination, articulation and sequencing of sounds.  The tests are designed to provide the examiner with considerable choice in individual application, but differential diagnosis calls for experienced clinical judgement.  Since the tests are not intended to produce pass/fail results, descriptive recording and clinical assessment on a three- or five-point scale is recommended.


Automatic operant response procedure ('play-test') for the study of auditory perception of neurologically impaired infants. Ten babies with cerebral palsy of varying types and degrees (age-range 10 to 27 months) participated in an initial exploratory study designed to determine the effectiveness of an automated, two-choice audio feedback system (Playtest') for evaluation of the auditory perception and processing capabilities of neurologically impaired infants.  The major components of the 'Playtest' are a master control unit and two toy-like switches which are attached to the baby's crib.  By playing with the 'toys', the baby is able to listen to one of two pre-recorded audio stimuli, music or a monotone hum.  Frequency and duration of the baby's self-selected listening responses are automatically recorded on meters inside the control unit and provide a precise numerical record over an extended period of time.  In this study the handicapped infants were physically able to operate the apparatus and demonstrated highly significant preferential listening.  Comparison of the recorded data from the study infants with those from normal infants showed no significant difference between the performances of the two groups.  The findings suggest that the 'Playtest' technique could be successfully applied to the objective assessment of auditory perception and processing abilities of neurologically impaired infants, whose handicaps often prevent them from effectively participating in other standardised test procedures.  The principal advantages of the technique are that testing is done in the child's most familiar environment--his own crib at home--without the intrusion of other people, and the evaluation of hearing competence is a function of the baby's spontaneous self-selected responses to sound variables, and hence of his auditory discrimination.


The isolation syndrome in childhood.

The isolation syndrome in childhood. A new diagnostic category--the Isolation Syndrome--is proposed to describe a pattern of abnormal behaviour in children.  The child's 'isolated' state manifests itself in defective social interaction and communication between mother and child, in disorders of perceptual function and motor skills, in stereotyped behaviour and in general developmental retardation, especially in language.  The typical situations in which the syndrome is likely to occur are discussed, and methods of treatment, both prophylactic and remedial, are given in detail.  The purpose of identifying the Isolation Syndrome is to alert clinicians to the possibility that in some children with abnormal patterns of behaviour there is a specific and treatable difficulty in the child's environment.


Trisomy-18 mosaicism with features of Russel-Silver syndrome. A child is described who presented at 16 months with developmental delay and clinical features of the Russell-Silver syndrome.  Chromosome analysis revealed trisomy-18 mosaicism.  Only one other similar case has been reported in the literature.  It is recommended that chromosomal studies continue to be included in the clinical investigation of children with Russell-Silver syndrome.


Tay-Sachs disease: case reports with emphasis on chromatographic study of rectal biopsy. Two South Indian Hindu children with typical clinical features compatible with Tay-Sachs disease are presented.  The identification of GM2 as the major ganglioside in the lipid extract of rectal biopsy helped to confirm the clinical diagnosis.


'Progressive cerebral palsy' or spinal cord tumor?  Two cases of mistaken identity. The misdiagnosis of cerebral palsy in children with neurological impairment is relatively common, although it is particularly untenable if the child's symptoms run a progressive course.  This paper reports two children with presumed 'progressive' cerebral palsy who at later evaluation were found to have intramedullary tumors of the cervical spinal cord.  The report is intended to alert pediatricians to the atpyical presentation and insidiuos progression of spinal cord tumors in children.  Whether or not the child has cerebral palsy, any progressive deterioration of function in the extremities, complaints of back pain, loss of sphincter control, or sensory abnormality, warrants a thorough neurological examination and specific radiological procedures to exclude the possiblility of a spinal cord tumor.


Congenital ophthalmoplegia and school achievement: a case study. A 6 1/2-year-old boy with Moebius' syndrome, with severely restricted horizontal eye movements, was found to have the visuo-motor integration of a child of three years (IQ equivalent 41) and the perceptual development of a child of four years 10 months (perceptual quotient 68).  Cognitive assessment revealed functioning in the low dull-normal range of ability (IQ equivalent 83).  Achievement in arithmetic and reading was found to be at late kindergarten and early first-grade levels respectively (IQ equivalents 83 and 92).  Thus the boy's achievement was in line with his cognitive ability and greater than 1 S.D. above his visual-perception and visuo-motor development.  The results of this study replicate the findings of Kalverboer et al. (1970) on a 12-year-old boy with Moebius' syndrome and add to a growing body of evidence which does not support the current emphasis on visuo-motor development and training in the diagnosis and remediation of learning difficulties.


Esophageal columnar epithelial beta-galactosidase and beta-glucuronidase. We have compared the activity of the lysosomal enzymes, beta-galactosidase and beta-glucuronidase, in esophageal columnar, gastric fundic, and small intestinal epithelia. Beta-Galactosidase activity in esophageal columnar epithelium was less than that in intestinal tissue. Beta-Glucuronidase activity in the esophageal columnar epithelium was greater than that in gastric fundic tissue. Thus, this unique epithelium has enzyme characteristics which are dissimilar to both intestinal and gastric fundic tissue. This tends to support previous findings that suggested a metaplastic derivation.


Long term effect of highly selective vagotomy on basal and maximal acid output in man. Basal acid output (BAO) and Maximal acid outputs (MAO) were measured 5 years after highly selective vagotomy (HSV) in 21 patients who had previously undergone serial testing of BAO and MAO for up to 2 years after HSV. BAO was found to have decreased from a mean of 1.7 mEq per hr, 1 year after HSV, to 1.4 mEq per hr, 5 years after HSV (not significant). The mean reduction in BAO at 5 years, compared with the preoperative BAO of 8.4 mEq per hr, was 79%. The mean peak acid response to pentagastrin (PAO-Pg) increased from 20.2 mEq per hr at 1 year to 22.6 mEq per hr at 5 years (0.1 greater than P greater than 0.05). The mean reduction in PAO-Pg, compared with the preoperative PAO-Pg of 43 mEq per hr, was 51% at 1 year and 48% at 5 years. Inasmuch as acid outputs seem unlikely to increase further after 5 years, it is concluded that HSV produces a permanent reduction of about 80% in basal acid output and 50% in maximal acid output.


Jejunal and ileal absorption of dibasic amino acids and an arginine-containing dipeptide in cystinuria. Ileal transport of dibasic amino acids has not previously been studied in the intestine of healthy volunteers or cystinuric patients. Experiments have therefore been designed to compare ileal and jejunal absorption of lysine and arginine both in normal subjects and cystinuric patients. In addition, jejunal perfusion experiments have been carried out to investigate absorption of the dipeptide L-arginyl-L-leucine. The results indicate that, at the concentrations studied (4.2 mM lysine, 1 mM arginine), severe transport defects exist throughout the whole small intestine for both amino acids in cystinuria. Despite the transport defect for free arginine, cystinuric patients absorbed the dipeptide L-arginyl-L-leucine normally. Because of the transport defect for free arginine, it has been possible to show that during absorption of L-arginyl-L-leucine in cystinuria approximately 30% of dipeptide-bound arginine can be recovered from the gut lumen in the free form. These findings indicate that the prime function of specific amino acid transport systems during the absorption of protein digestion products may be as a "recapture mechanism" for amino acids liberated as a result of mucosal cell peptide hydrolysis.


Fecal radioiodide excretion following intravenous injection of 131-I-albumin and 125-I-immunoglobulin G in chronic inflammatory bowel disease. An aid to topographic diagnosis. Simultaneous studies with 131-I-albumin and 125-I-immunoglobulin G (IgG) were made in 48 cases of chronic inflammatory bowel disease. Twenty-one had ulcerative colitis and 27 had Crohn's disease which was confirmed at laparotomy in every case. Intestinal protein loss was measured simultaneously by means of 59-Fe-iron dextran in 44 patients. All patients had abnormal intestinal protein loss. A high correlation was shown between fecal 59-Fe clearance and fractional catabolic rate of albumin, confirming the validity of 59-Fe-iron dextran as a test substance to measure intestinal protein loss. Fecal radioiodide excretion of 131-I from 131-I-albumin (A) and 125-I from 125-I-IgG (G) was significantly different in ulcerative colitis and Crohn's disease. The ratio G/A was close to unity (smaller than 1.60) in ulcerative colitis and Crohn's disease with exclusive or predominant involvement of the colon, whereas it was high in Crohn's disease of the small intestine and highest in cases with jejunal involvement. Thus, the ratio may be valuable in topographic diagnosis of chronic inflammatory bowel disease. A high ratio was found in 2 patients with Crohn's disease of the small intestine and normal radiography of the small intestine, and a low ratio was present in 7 cases of ulcerative colitis with normal radiographic findings. In all 9 patients with normal radiography, fecal 59-Fe clearance was elevated as evidence of abnormal intestinal protein loss. No correlation was present between the size of protein loss and the pathoanatomic extent of the lesions on subsequent laparotomy in 25 patients with Crohn's disease. Fecal radioiodide excretion (131-I from 131-I-albumin and 125-I from 125-I-IgG) was positively correlated with diarrhea (daily stool mass) in both ulcerative colitis and Crohn's disease. Intestinal protein loss was not.


Electrophysiological effects of burimamide and 16,16-dimethyl prostaglandin E2 on the canine gastric mucosa. The electrophysiological effects of two potent inhibitors of gastric acid secretion, burimamide and 16,16-dimethyl prostaglandin E2 (dm-PGE2), were determined in an in vivo histamine-stimulated canine stomach preparation and an in vitro canine gastric mucosal preparation. In the in vivo stomach preparation, intravenous burimamide caused a decrease in acid secretion, an increase in transmucosal potential difference (PD) and the relative resistance (R) was essentially unchanged. Intravenous dm-PGE2 also inhibited acid secretion and increased PD but, in contrast to burimamide, increased R. In the in vitro preparation, the unidirectional flux of sodium from mucosa to serosa increased after dm-PGE2 but not after burimamide. Passive sodium fluxes and unidirectional chloride fluxes were not altered after either agent. These findings suggest that increased active transport of sodium from mucosa to serosa is at least partially responsible for the observed increase in transmural PD with dm-PGE2, an agent which also decreases hydrogen ion transport. With burimamide the increased PD was due primarily to inhibition of hydrogen ion secretion.


Analysis of the motor effects of 13-norleucine motilin on the rabbit, guinea pig, rat, and human alimentary tract in vitro. Motor effects of 13-norleucine motilin (13-Nle-M), a synthetic analog of motilin and biologically equivalent to the natural polypeptide, on the rabbit, guinea pig, rat, and human alimentary tract were investigated in vitro. Whereas guinea pig and rat preparations proved refractory to 13-Nle-M action, muscle strips of the stomach and upper small intestine from rabbits and man were highly sensitive to 13-Nle-M, contractile responses being elicited with concentrations of less than 2 times 10-minus 9 M. Although circular muscle from rabbit colon responded to 13-Nle-M, Taenia coli preparations were unaffected by the polypeptide; in man, the reverse was observed. Gallbladder, uterine, and vascular smooth muscle were unresponsive to 13-Nle-M. Pharmacological analysis revealed that the effects of 13-Nle-M on the gastrointestinal muscle are not mediated via nervous pathways: ganglion blockade by hexamethonium, blockade of axonal conduction by tetrodotoxin, or anticholinergic action by atropine failed to affect 13-Nle-M actions. It was therefore concluded that 13-Nle-M caused contractions by stimulating receptors on or in the muscle cell. By use of the antihistaminic pheniramine, histamine receptors could be differentiated from the site of 13-Nle-M action. As the contractile response to 13-Nle-M was abolished by the Ca++ antagonistic compound verapamil, a role for 13-Nle-M in the transport of Ca++ to the cytosol of intestinal smooth muscle might be considered.


Mechanism and site of small intestinal absorption of alpha-tocopherol in the rat. The site and mechanism of alpha-[5-methyl-3-H]tocopherol absorption was investigated using everted rat small bowel sacs incubated in a micellar medium. Mean plus or minus SE absorption rates of the vitamin at 300 muM incubation solution concentration by proximal, medial, and distal small bowel segments were 2.2 plus or minus 0.17, 3.4 plus or minus 0.21, and 2.0 plus or minus 0.04 nmoles per min per 100 mg, respectively. Addition of 2,4-dinitrophenol, sodium azide, or potassium cyanide to the incubation medium in separate experiments did not change the rate of absorption (P greater than 0.10). Stepwise increase in incubation solution tocopherol concentration up to 1200 muM resulted in a linear increase in the absorption rate. In all of the above described experiments the rate of absorption of the vitamin by the medial portion of the small bowel was significantly (P smaller than 0.01) higher than the rate of absorption of the vitamin by the proximal and distal small bowel segments. No transmural transport of the vitamin into the serosal compartment took place. Autoradiographic examination of the tissue after incubation disclosed accumulation of the vitamin in the submucosal lymphatic spaces. Alpha-Tocopherol absorption by the rat small bowel appears to be a passive diffusion process taking place at the highest rate in the medial portion of the small bowel.


Electrical spiking activity and propulsion in small intestine in fed and fasted rats. Bipolar electromyograms were obtained from electrodes chronically implanted on the small intestine in rats accustomed to receiving food only during 4 days per week. Continuous recording, begun 5 to 10 days after operation, continued for 10 to 15 days. The spiking activity was continuously summed at 20-sec intervals on linear integrators. At the end of the experiment, small intestinal propulsion and gastric emptying were measured. During fasting, the pattern of spike bursts of the jejunum was a cycle of three phases: a period of silence was followed sequentially by periods of irregular and regular spike bursts, lasting 6 to 10 min and 4 min, respectively. Cycles recurred at intervals of 16 to 20 min and migrated caudad at 2 to 3 cm per min. Intragastric administration of food and amino acids caused continuous irregular spiking for 2 to 3 hr. A similar effect resulted from amino acids and glucose administered into the duodenum. Continuous but weak irregular spiking followed intragastric or intraduodenal administration of oleic acid. In fasted rats, the velocity of intestinal transit was faster when a bolus was administered before a migrating complex than after Marker movement was rapid in fed rats in whom there was continuous irregular spiking. The presence of nutrients in the intestinal lumen alters the patterns of contractions.


Effect of perfusion rate on absorption, surface area, unstirred water layer thickness, permeability, and intraluminal pressure in the rat ileum in vivo. Intestinal absorption and intraluminal pressures were measured at perfusion rates between 0.3 and 200 ml per min in the rat ileum in vivo. Glucose absorption from a 72 mM glucose solution and tritiated water ([3-H]water) diffusion rate were used to reflect changes in mucosal surface area. Glucose absorption from a 4 mM solution was used to indicate changes in unstirred water layer thickness, and mannitol and urea absorption were used as markers of passive mucosal permeability. In a partially obstructed intestinal segment, designed to keep the gut partially filled even at low perfusion rates and to minimize surface area change as perfusion rate was increased, glucose absorption from a 4 mM solution increased by 150% as perfusion rate was increased from 1 to 100 ml per min. Forty per cent of this increase was due to increased surface area (estimated from the change in [3-H]water absorption), and 110% of the increase is attributed to thinning of the unstirred water layer. Because mannitol absorption was zero at all perfusion rates, none of the enhanced glucose absorption rate need be attributed to enhanced mucosal permeability, even though intraluminal pressure was increased at higher perfusion rates. Urea absorption was apparently influenced by surface area and by permeability changes, but not by the thickness of the unstirred water layer. This model was also used to explore the effect of unstirred water layer thickness on the inhibitory effect of sodium replacement by magnesium on glucose absorption from a 4 mM glucose solution. Inhibition by sodium removal was equal at 1, 10, 100, and 200 ml per min perfusion rates, suggesting that unstirred water layer thickness does not play an important role in the interaction of glucose and sodium absorption when intraluminal sodium concentration is reduced. Additional experiments in an unobstructed ileal segment revealed that the major effect of enhanced perfusion rate is to increase mucosal surface area; relatively high rates of perfusion were required to thin significantly the unstirred water layer when intestinal outflow was not partially obstructed.


Effect of ethanol on sodium-dependent glucose transport in the small intestine of the hamster. The objective of this study was to investigate the mechanism by which ethanol inhibits intestinal absorption of sugars. In vitro experiments on hamster jejunum have shown that the presence of ethanol in the mucosal solution caused an inhibition of the net transport of water and glucose. There was also a decrease in the intracellular water content and an increase in the intracellular sodium and potassium concentration of the gut tissue. In contrast, the intracellular glucose concentration decreased in the presence of ethanol. These ethanol-induced changes were directly related to the ethanol concentration of the mucosal solution. In the presence of 450 mM (2%) ethanol in the mucosal solution, there was also a significant inhibition of transmural potential difference, estimated glucose metabolism, and both unidirectional fluxes of sodium. The net flux of sodium to the serosal side however did not decrease significantly. These effects of ethanol cannot be fully explained by its osmotic action, and it is suggested that the ethanol-induced reduction in glucose transport could be mainly the result of an interference with the carrier-mediated coupled entrance of glucose and sodium across the brush border. A depression of cellular metabolism could also have played a role in this process.


Comparison of secretin and vasoactive intestinal peptide on pancreatic secretion in dogs. Vasoactive inhibitory peptide (VIP) and secretin were compared in regard to the stimulation of pancreatic bicarbonate secretion and the augmentation of pancreatic response to caerulein or a peptone meal in chronic gastric and pancreatic fistula dogs. Dose-response analysis showed that maximal bicarbonate response to VIP was about 17% of that to secretin. Both caerulein and endogenous cholecystokinin, released by a peptone meal, clearly potentiated pancreatic bicarbonate response to VIP in a manner similar to secretin. The interactions of these two peptides showed that VIP is a potent inhibitor of secretin-induced pancreatic secretion. From the dose-response curves to secretin alone and secretin plus VIP, Michaelis-Menten analysis showed typical competitive inhibition, which indicates that VIP and secretin share a common receptor site.


Effect of hormones on pancreatic macromolecular transport. The role of subcellular organelles in the synthesis, transport, and secretion of pancreatic digestive proteins has been well documented. This study was designed to examine effects of pentagastrin, secretin, and acute and chronic administration of cholecystokinin-pancreozymin (CCK-PZ) on pancreatic macromolecular transport and secretion. Pooled rat pancreas slices were pulse-labeled with L-[14-C]phenylalanine and migration of 14-C-labeled proteins studied by "chase" incubation for 15, 30, 60, and 120 min. After in vitro incubation of control and drug-treated pancreatic slices, subcellular particles were isolated by differential centrifugation; Specific activity of radioactive labeled proteins was determined in subcellular fractions involved in transport and secretion of digestive proteins. These studies indicate that pentagastrin and acute and chronic stimulation with CCK-PZ did not alter the rate of transport of labeled proteins from ribosomes to the zymogen granules. Pentagastrin and CCK-PZ stimulated secretion of labeled proteins from the zymogen granules into the medium in the concentrations used as evidenced by significant increase in the amount of labeled proteins in the medium and significant decrease in the specific activity of the zymogen granule fractions after 60- and 120-min periods of incubation. Secretin did not alter the rate of transport or secretion of the pulse-labeled proteins.


Plasma disappearance of radioactivity after intravenous injection of labeled bile acids in man. The kinetics of disappearance of radioactivity from plasma after intravenous injection of radiolabeled bile acids was characterized in healthy subjects. Cholic and chenodeoxycholic acids and their N-glycine and N-taurine conjugates were studied along with the secondary bile acid, deoxycholic acid, and a synthetic conjugated bile acid, dehydrocholyltaurine. Disappearance of each primary bile acid was rapid and could be described by a biexponential curve (t 1/2 the first component, 1.7 to 3 min; second component, 7 to 16 min). Cholyglycine and cholyltaurine had identical disappearance rates which were significantly faster than the disappearance rates of chenodeoxycholylglycine and chenodeoxycholyltaurine, which were also identical. Radioactivity of a conjugated bile acid disappeared more rapidly than that of its unconjugated form, but all of these differences, although consistent, were small. Deoxycholic acid radioactivity disappeared slightly more slowly than that of the primary bile acids. In vitro, dihydroxy bile acids were bound by serum proteins more completely (96 to 98%) than trihydroxy bile acids (83 to 91%), whether free or conjugated, and binding was unrelated to bile acid concentration. Thus, plasma disappearance rates were related to the degree of protein binding to some degree in that those bile acids which were more tightly bound had the longer t 1/2 values. However, dehydrocholyltaurine showed little protein binding (42%), yet had the slowest disappearance rates; t 1/2 values averaged 4 and 36 min for the two components of the disappearance curve. The results suggest that the residence time of any bile acid in blood is extremely short, and that measurable concentrations of serum bile acids persist only because of continuous intestinal absorption. It is speculated that the reported difference between the pattern of fasting state serum bile acids and biliary bile acids is explained by differences in intestinal absorption and hepatic uptake of individual bile acids.


Effect of decreased gallbladder stimulation on enterohepatic cycling and kinetics of bile acids. The effect of diet on the rate of enterohepatic recycling and bile acid kinetics was studied in groups of human subjects by reducing dietary protein and fat. The effect on enterohepatic cycling was assessed indirectly in control subjects, in patients with cholesterol cholelithiasis, and in patients with cholecystectomy by comparing output of breath 14-CO2 after the administration of a trace of cholyl [1-14-C]glycine during two periods: a control period when three meals containing protein and fat were eaten daily and a diet period, when protein and fat were excluded from the diet. Breath 14-CO2 output was not altered by diet in the patients with cholecystectomy. In the healthy subjects and in the patients with cholesterol cholelithiasis breath 14-CO2 output fell by approximately 50%, indicating that decreased endogenous cholecystokinin-pancreozymin stimulation had reduced but not eliminated enterohepatic recycling. Bile acid kinetics after administration of [2,4-3-H]cholic acid and [24-14-C]chenodeoxycholic acid were measured in 6 healthy subjects during a control period, when they ate a diet containing three daily meals containing fat and protein, and again not less than 4 months later during the 4th week of a diet during which they ate only one meal containing fat and protein every other day. tthe pool size of cholic and chenodeoxycholic acid rose significantly during the diet as did the total bile acid pool size. The daily fractional turnover rate of both primary bile acids fell significantly during the diet, but their synthesis rate was not significantly changed. It is concluded that (1) significant enterohepatic circulation of bile acids occurs even in the absence of dietary stimuli for gallbladder contraction; and (2) diet may significantly affect bile acid pool size and fractional turnover, while bile acid synthesis remains essentially unchanged.


Persistent hypotension and intestinal infarction in a patient with primary amyloidosis. A patient with primary amyloidosis and the nephrotic syndrome had diarrhea and gastrointestinal bleeding probably due to intestinal ischemia. He died with extensive intestinal infarction. The infarction was most likely caused by decreased splanchnic perfusion secondary to the chronic hypotension of the nephrotic syndrome and to amyloid deposition within the walls of the small blood vessels supplying the gut. Although amyloidosis was suspected prior to death, a fixation artifact probably prevented the correct antemortem biopsy diagnosis.


Gallbladder and liver infarction occurring as a complication of acute bacterial endocarditis. A case of acute bacterial endocarditis is presented in which gallbladder infarction and areas of hepatic infarction were documented. Selective angiography showed findings consistent with emboli to the gallbladder and hepatic circulations.


[Perinatal mortality in foreign workers (author's transl)]. From 1970 to 1972, there were 216 perinatal deaths among 5595 newborns at the I. Frauenklinik der Universität München. 54 of these deaths were children of foreign workers (so-called "Gastarbeiter"). The data have been processed on punch cards and analysed by a computer. The differences noted underwent significance testing by the CHI-Quadrat test. Only statistical significant results are published. The perinatal mortality in the above period shows no difference between foreign and German ward patients. There is, however, a significant lower perinatal mortality in private patients. We feel that this difference is due to a significant lower rate of prematures in the private patient group. The cocial status as well as higher interest and motivation in health resulting in better prenatal care are discussed as causal reasons for this fact.


[The attitude of women to prophylactic hysterectomy (author's transl)]. The attitude of women to prophylactic hysterectomy (pH) after age 40 was investigated in 324 women in our out-patient clinic by a questionnaire taking into account psychological and sociological data. More than 50% of the women were against a prophylactic hysterectomy. This negative attitude cannot be explained by a desire for child bearing since only prophylactic hysterectomy after 40 was discussed. Other factors are important. The knowledge of the women about their reproductive organs was limited. One third of the patients thought the uterus is responsible for the production of sexual hormones and 3/4 of the women expected a hormonal imbalance following hysterectomy. The greater the ignorance the more frequent was the negative attitude to prophylactic hysterectomy (S 5%). 2/3 of the women ascribed a life long importance to the uterus and were against prophylactic hysterectomy (S 5%). 1/4 of the patients described the uterus as an organ important for sexual intercourse and therefore were against prophylactic hysterectomy (S 5%). It is understandable that 2/3 of the women thought of hysterectomy as a procedure which would have a negative or very negative influence on their lives (S 5%) when women ascribed to the uterus frequently a significance in hormone production or in sexuality in addition to the child bearing function of the uterus. Only approximately 1/3 of the women would feel of themselves as full women after a hysterectomy. Not quite 1/2 of the patients thought of the sterility following hysterectomy as a positive feeling and were more often accepting of the thought of a prophylactic hysterectomy (S 1%). Women who felt that they could talk about problems of their female genital organs with their partners had more often a negative attitude to prophylactic hysterectomy (S 1%). About 2/3 of the patients stated they would wish to have their partner present during a pre-operatitive discussion of a necessary hysterectomy. Only 1/4 of the patients were sure that a hysterectomy would not have a negative effect on their marital lives. Among the psychological factors, intelligence was of importance in the attitude to prophylactic hysterectomy. The more intelligent the woman, the more frequently she had a negative attitude to prophylactic hysterectomy (S 0.1%). There was no statistically significant correlation between personality factors according to Eysenck and the attitude to prophylactic hysterectomy. The older women more frequently accepted the thought of prophylactic hysterectomy (S 10%). The results were all tested statistically by the X2 method. A prophylactic hysterectomy should not be done without a thorough discussion of the attitudes and the expectational anxieties to such an operation.


[Deliveries in foreign women (author's transl)]. Within four and a half years (between January 1, 1969 and June 30, 1973) there were 6329 deliveries, among them 1217 confinements occurred in foreign women, i.e. proportional 19, 2%. The chi square method was used for the statistical analysis. The incidence of Caesarean Section in foreign women (5, 3%) is significantly higher than in German women (3, 4%). Just so, the incidence of Caesarean Section in wives of foreign workers from Spain and Portugal was significantly higher than in German women; it looks like as if the indication "Pelvic contraction" appears significantly more frequent in parturients of the western part of the mediterranean area than in German women. On the contrary, the indication "fetal distress" is significantly higher in the deliveries of the wives from Greece and Turkey (the eastern part of the mediterranean area). There was no statistical difference in the rate of forceps deliveries and deliveries by vacuum between the German collective (6, 1%) and the foreign collective (7, 5%). Statistically proved, the incidence of the incidence of the indication "fetal distress" in vaginal-operative deliveries of women from Turkey was higher compared to the German collective. Vice versa it turned out that the incidence of the indication "standstill on floor of the pelvis" occurred more often in German parturients than of the collective of Turkey. There was a second statistical method (randomization) to check up if the collectives are comparable; there exists a significant difference between German parturients and women from Turkey: in the German collective are more young and old I.-Parae, in the collective from Turkey you find more Multiparae and more wives in the optimal obstetrical age between 18 and 30 years. The subsequent obstetrical aspects and consequences are discussed. There was no significant difference between foreign and German parturients in further perinatal examinations and parameters.


[Influence of age on risk-factors during pregnancy, delivery and puerperium of primiparae (author's transl)]. The course of pregnancy and delivery of 600 primiparae is being reported. These were divided into four age groups: very young primiparae (14-16 years of age, Group I), older primiparae (35-39 years of age, Group III) and old primiparae (40 years and more, Group IV). These age groups are being compared to a collective of primiparae, by whom the delivery took place at an age between 17 and 34 years (Group II). In these age groups the difference in complication rate during pregnancy, delivery and puerperium is demonstrated. The differences were statistically secured by means of X-2-test. The very young primipara shows the least tendency to delivery complications, still her pregnancy should be considered more risky as compared to Group II, owing to the higher rate of gestosis and the tendency to premature delivery. Groups III and IV show a rising risk rate with increasing age in regard to gestosis (10, 8-30, 8%) and premature delivery (15, 4-28, 6%); also the higher rate of operational delivery was significant (38, 9-44, 6%). The highest risk rate is to be expected in women, who deliver the first time at an age above 40 years. Also the perinatal mortality of newborn is at its highest in this group.


Sex determination in bees. II. Additivity of maleness genes in Apis mellifera. Twenty-two randomly taken morphological characters were used in order to estimate the Mahalanobis generalized distance between diploid males, diploid workers, haploid males and triploid workers. It was found that adult diploid males are metamales and triploid females are slightly masculinized. These facts indicate that the maleness genesare slightly additive.


An analysis of the mode of gene action affecting pupa weight in Tribolium castaneum. Triple-testcross experiments (Kearsey and Jinks 1968) were employed to investigate the mode of gene action affecting pupa weight in Tribolium castaneum. Their experimental design involves two inbred lines, the F1 progeny and a segregating population derived from the cross of the inbred lines. In the present experiments, four segregating populations were used. These populations included the F2 generation, a select line (SEL) and two relaxed select lines (RSI and RSII). In addition, all possible reciprocal crosses were made among the RSI, RSII, and SEL populations. It was observed that: (1) additive, dominant and epistatic gene effects all made significant contributions to the pupa weight of the progeny from all four segregating populations: (2) there was no evidence of either accumulation of epistasis as a result of selection in the SEL population or decline in epistasis as a result of removing selection pressure from the RSI and RSII populations; and (3) significant negative heterosis and maternal effects contributed to the pupa weight of the crossbred progeny of the RSI, RSII and SEL populations.


Geographical distribution of twelve transferrin alleles in black rats of Asia and Oceania. About 450 black rats (Rattus rattus) were collected from 25 localities in Asia and Oceania. Their serum transferrins were analyzed by a newly developed thin layer acrylamide gel electrophoresis accompanied with acrinol pretreatment, exhibiting 12 transferrin bands. Generally, Asian type rats (2N=42) had fast-moving transferrins (R-series), Ceylon type (2N=40) moderately moving ones and Oceanian type (2N=38) slowly moving ones (C-series). Exceptionally, in northern India and Pakistan all Asian-type rats had C-series Tf. The possibility that divergence of R-series Tf and C-series Tf  had proceeded the karyotypic differentiation from 42 to 38 is proposed. In combination with the previous molecular data, the time of the divergence is roughly estimated between the order of a million years and ten thousand years.


Population size and selection intensity effects on long-term selection response in mice. Long-term response to within full-sib family selection for increased postweaning gain was evaluated in lines having different effective population sized (Ne) and selection intensities (i). Line designations were I4(4), I8(2), I16(2), M4(4), M8(2) and M16(2), where I and M indicate selection of the top 50% and 25%, respectively; 4, 8 and 16 represent the number of parental pairs per replicate and number of replicates is given in parentheses. Realized within full-sib family heritabilities (hR-2) in the first phase of selection (0-14 generations) were larger in 16-pair lines than in 4- and 8-pair lines. In the second phase of selection (greater than 14 generations), hR-2 declined significantly (P smaller than .01) in all lines, and only the I16 and M16 lines had hR-2 values significantly (P smaller than .01) greater than zero. Realized genetic correlations involving number born, 12-day litter weight, weaning weight and six-week weight tended to decline in the second phase of selection. The I16, M16 and control (C16) replicates were crossed in all combinations at generation 14. Crosses were then selected within litters for high postweaning gain. The hR-2 values in the crossbred lines were all larger than those in the second selection phase for M16-1. M16-2 and I16-1, but not for I16-2. Within each Ne level, total response was significantly (P smaller than .01) less for I lines compared with M lines. Total response increased as Ne increased, within each level of i. Relatively small differences in realized i values among Ne lines could not account for this result. The difference in total response among the Ne lines at a given selection intensity may be due to inbreeding depression and a combination of interactions involving "drift" and selection. By crossing replicates of the M lines with the C16 control, the effects of inbreeding depression were removed. Inbreeding depression and genetic drift, as defined herein, were equally important in accounting for differences among Ne lines in total response.


Enzyme polymorphisms: gene frequency distributions with mutation and selection for optimal activity. Gene frequency distributions observed in large-scale surveys of species of Drosophila are shown to be incompatible with a genetic model involving neutral mutations and genetic drift alone. The data are, however, qualitatively similar to predictions based on an alternative model of natural selection for an optimal level of enzyme activity in addition to drift and mutation. The intensity of selection detected reduces the mean rate ofgene substitution to less than one-quarter that expected on the neutral-allele hypothesis.


Selection in complex genetic systems III. An effect of allele multiplicity with two loci. A two-locus model with three alleles at one locus and two at the other is studied. The viability system is such that all double heterozygotes have fitness unity, all single heterozygotes have fitness w smaller than 1 and all double homozygotes have fitness w-2. The following are the major findings: 1. There are more stable equilibria for tight linkage than in the corresponding three-locus model, even though the number of chromosomes is lower. 2. The equilibria stable for tight linkage do not belong to a unique high complementarity class, as is the case for two alleles at each locus. Instead the strength of selection determines the structure of the equilibrium. 3. The increase in number of alleles seems to reduce the possible extent of association between the loci. 4. The measure of this association is not well defined, although we have suggested a statistically standard way of getting over this. 5. A mutation introduced while a population is in linkage disequilibrium may, per medium only of the change in number of alleles, destroy the linkage disequilibrium.


Mutator genes and selection for the mutation rate in bacteria. Gene frequencies in populations of haploid, asexual organisms are described by linear recurrence equations. Several models in which the mutation rate is controlled by one locus and the fitness is controlled at one or more other loci are developed. It is shown that good approximations can be introduced to give explicit solutions for the course of selection in these models. It is shown that a strong non-equilibrium selection for mutator genes is possible even when the presence of such a gene decreases the fitness of an individual. Experiments that corroborate these conclusions are discussed along with the effects of population size that determine the applicability of these results to natural populations.


How many genes are selected in populations of Dacus oleae. Three natural populations of Dacus oleae have been sampled for six electrophoretically detected polymorphic genes. The distribution of the allele frequencies in the different populations were analyzed by the method suggested by Lewontin and Krakauer (1973) (the various in space one) in order to test for selective neutrality. This method, however, which in our case showed that one or more genes are or have been subjected to selection, does not permit estimation of the number of selected loci. An improvement of this method is proposed that perimts a minimum estimation of the selected genes. About a third of them seem to be selected in our material. In our case however, where a cytological analysis is not possible, genes are not differentiated from possible inversions including these genes.


Polyallelic mutational equilibria.

Polyallelic mutational equilibria. A new deterministic formulation is derived of the equilibrium between mutation and natural selection, which takes into account(a) the possibility of many allelic mutation states, (b) selection coefficients of the order of magnitude of the mutation rate and (c) the possibility of further mutation of already mutant alleles. The frequencies of classes of alleles 0, 1, 2, n mutant steps removed from the type allele are shown to form a Poisson distribution, with a mean and variance of the mutation rate divided by the coefficient of selection against each incremental mutational step.--This formulation is interpreted in terms of the expected frequencies of electromorphs, defined as classes of alleles characterized by common electrophoretic mobilities of their protein products. Electromorph frequencies are predicted to form stable unimodal distributions of relatively few phenotypic classes. Common electromorph frequencies found throughout the ranges of species with large population sizes are interpreted as being a uniquely electrophoretic phenomenon; band patterns on starch and acrylamide gels are phenotypes, not genotypes. It is predicted that individual electromorphs are highly heterogenous with regard to amino acid sequence.


Chemotaxis-defective mutants of the nematode Caenorhabditis elegans. The technique of countercurrent separation has been used to isolate 17 independent chemotaxis-defective mutants of the nematode Caenorhabditis elegans. The mutants, selected to be relatively insensitive to the normally attractive salt NaCl, show varying degrees of residual sensitivity; some are actually weakly repelled by NaCl. The mutants are due to single gene defects, are autosomal and recessive, and identify at least five complementation groups.


The genetics of Drosophila subobscura populations. V. A study of linkage disequilibrium in natural populations between genes and inversions of the E chromosome. The genetics of Hk and Est-9 complex gene have been studied in Drosophila subobscura. While Hk alleles mendelize normally, Est-9 is a complex locus consisting of several very closely linked genes with active and silent alleles. Both genes are located on chromosome E; a detailed genetic map was constructed with the help of visible markers and inversions. Both Hk and Est-9 are included in or are very near to inversions of the E chromosome. While Hk does not show linkage disequilibrium either with Est-9 or inversions, Est-9 does show disequilibrium in two ways: both with inversions and between different Est-9 genes. All natural populations studied show the same kind of association between Est-9 gene combinations and inversions. It is argued that these results are better explained by selection than by neutrality.


The evolution of selectively similar electrophoretically detectable alleles in finite natural populations. Most of the models of population genetics are not realistic when applied to data on electrophoretic variants of proteins because the same net charge may result from any of several amino acid combinations. In the absence of realistic models they have, however, been widely used to test competing hypotheses about the origin and maintenance of genetic variation in populations. In this paper I present a general method for determining probability generating functions for electrophoretic state differences. Then I use the method to find allelic state difference distributions for selectively similar electrophoretically detectable alleles in finite natural populations. Predicted patterns of genetic variation, both within and among species, are in reasonable accord with those found in the Drosophila willistoni group by Ayala et al. (1972) and by Ayala and Tracey (1974).


Influence of diet and age on ribonucleic acid, protein and free amino acid levels of rat skeletal muscle. The relationship of dietary protein to RNA, protein and free amino acids in the growth of rat gastrocnemii (GN) muscles over 4, 8, and 12 week periods, was investigated in male weanling rats. The N content of casein diets, C-1, C-2, and C-3 was 0.76, 1.41 and 2.88% while that of the supplemented wheat (SW) diet was 2.5%, respectively. The decrease in concentration of RNA with age was significantly influenced by diet. Accumulation of RNA over a period of time was also influenced by diet, for the C-1 diet permitted only limited accumulation and the C-2 and SW diets restricted accumulation to within 80% of that of the C-3 diet. While protein concentration was affected more by age than by diet, accumulation was influenced by diet, greatest quantities being found in C-3 and SW rats throughout the experimental period. Changes in free amino acid concentration of GN muscles also occurred with age and reflected quantitatively the C-2 and C-3 dietary amino acid patterns. The high levels of certain amino acids in C-1 rats, however, were typical of those found during periods of restrictive protein intake. All criteria of measurement indicated growth and development were greatly restricted by the C-1 diet, less restricted by the C-2 diet while the C-3 diet permitted normal growth.


Growth and lipid metabolism in genetically different types of calves in a tropical environment. Growth rates were compared in suckling Britves of cows grazing in a tropical environment. The plasma lipid composition of calves and their dams was examined at intervals from 14 weeks post-partum to 3 weeks post-weaning. Growth rates from birth to weaning were significantly higher (P less than 0.01) in zubru than in British calves. Plasma concentrations of cholesterol and phospholipid were always higher in zebu than in British calves and in Brahman cross calves increased from 14 to 19 weeks of age followed by a decline prior to weaning at 30 weeks old. There were only small changes in the concentrations of these constituents in Africander cross and British calves during this period. At 3 weeks post-weaning the plasma concentrations of cholesterol were lower (P less than 0.01) than the pre-weaning levels in all calves. The concentrations of cholesterol, phospholipid and total ketones were higher (P less than 0.01) in zebu than in British cows. There weer significant relationships between plasma concentrations of cholesterol and growth rates in zebu calves and between growth rates of calves and the plasma cholesterol concentration of their dams in all breeds. The results suggest the possibility of using plasma cholesterol concentrations as indices of lactational status and growth rates of calves.


Model for the growth of a solid in vitro tumor. A model for the growth of a tumor by diffusion is considered for spheroids which are grown in a normal medium in suspension culture. The experimental evidence indicates that, upon the onset of necrosis in the centre of the spheroid, the viable rim thickness decreases relatively slowly. This evidence contradicts the results of the usual model in which the oxygen consumption per unit volume is assumed to be constant. The proposed model assumes that the oxygen concentration is constant above a critical value, and proportional to the concentration below this critical value. The viable rim thickness of the spheroid, as a function of the necrotic radium, varies markedly over the range of the parameters in this model. By suitably choosing these parameters, the results of this model agree with the experimental evidence.


Changes in water, protein, sodium, potassium, and chloride in tissues with growth of the beagle. Changes in total body and tissue composition of 43 beagles were analyzed from 0 day (birth) to 1 year. The tissues studied were skeletal muscle, viscera (heart, lungs, gut, liver, kidneys), skeleton, skin, and brain, and the data were expressed as follows: fat-free tissue weight (FFTW) as a per cent of total fat-free wet weight (FFWW); water and protein in grams per kilogram FFTW; and Na, Cl, K in milliequivalents FFTW. The mass of skeletal muscle increased from 21% of FFWW at birth to 36% at 1 year while the contribution of the remainder of the tissues decreased: skeleton from 30 to 25%, viscera 23 to 15%, skin 18 to 13%, and brain 4 to 0.9%. Over the same period, total body water decreased from 780 g/kg to 665, water of skeletal muscle from 771 to 665, of viscera from 782 to 621, of skeleton from 644 to 424, of skin from 765 to 669, of brain from 853 to 692; Total protein increased from 113 g/kg to 196, in skeletal muscle from 122 to 253, in viscera from 114 to 195, in skeleton from 71 to 112, in skin from 170 to 227, and in brain from 63 to 164. Total Na was 84 mEq/kg throughout the first year of growth, 101 for skeleton, and 89 for skin, while Na increased in viscera from 66 to 75 and in brain from 63 to 77, but decreased in skeletal muscle from 75 to 59. Total K increased from 31 mEq/kg at birth to 62 at 1 year, and from 38 to 107 in skeletal muscle, from 49 to 78 in viscera, and decreased from 27 to 11 in skin, and 42 to 122 in brain. Total Cl decreased from 58 to 49, in skeletal muscle from 52 to 34, in skeleton from 43 to 33, while that in viscera increased from 56 to 78. The contribution of skeletal muscle and viscera (the major metabolic cell mass) to total FFWW increased from 44 to 52%, and it contributed over 50% of total water, protein, Cl, and 89% of K. Skeletal muscle accounted for the increases. Skin and skeleton contributed 38% of FFWW, 17% of water, 29% of Na, 19% of Cl, 16% of protein, and 10% of K. The rates of change in these parameters fell into three patterns: (1) the content of the chemical component did not change significanly in the first year of growth; (2) it increased or decreased at a constant rate; or (3) there were two rates at which the concentration changed; the break between them occurred between the third and fourth months and coincided with evidence of increasing sexual maturation. A specific pattern of change was characteristic of a particular tissue and appeared independent of that of the total dog and other tissues. These data support the conclusion that there are mechanisms intrinsic to each tissue which exert a degree of control during growth over its chemical composition; therefore, growth itself can be considered an intrinsic regulatory mechanism.


Increase in rat liver ribonuclease inhibitor levels during the neonatal period. Alkaline ribonuclease (RNase) activity in nuclear, mitochondrial, and cytoplasmic fractions of rat liver is higher in newborn animals than in young adults. The level of cytoplasmic RNase inhibitor is low in newborn rat liver and increases more than two fold by 10 days of age.


Skeletal growth and development of achondroplastic mice. Skeletal development of achondroplastic (cn/cn) mice, aged 2 to 7 weeks, was investigated and compared with that of equally old non-achondroplastic sibs. Differences in body weight and dry weight of femora, tibiae, humeri, and unlae, and in the length of tibiae, unlae, and humeri became more marked with advancing age. Of the biochemical assays carried out, only those for sialic acid and hydroxyproline disclosed significant differences between dwarfs and non-dwarfs, all dwarfs having higher levels of hydroxyproline, and most of them having higher sialic acid levels than the non-dwarfs. Histologically, no distinction could be made between growth zones of non-dwarfs, of cn/+, or +/+ genotype. Among the dwarfs, two groups differing as to the severity of the skeletal abnormality could be distinguished. The differences between dwarfs were most marked in the growth zones of tibiae and femora, less conspicuous in those of vertebrae and least pronounced at the chondro-osseous junction of the ribs. The cause or causes of the histologic heterogeneity remain unknown.


Effects of light environment on the weight of bursa of Fabricius in White Rock chicks. The weight of the bursa of Fabricius of White Rock chicks reared under two photoperiods was studied in relation to body weight, weight of the endocrine organs, and spleen using a multiple correlation method. At the 95% level of confidence the coefficient of determination suggested that the weight of the bursa could be predicted with 77% plus or minus 7.8% accuracy from the organs weighed for a period from 2-24 weeks, the weight of the pituitary being the most stable contributor to this prediction. The weight of the spleen, similarly, could be predicted with a 92% plus or minus 3.8% accuracy. Correlations of testes and thyroid weight with bursa weight suggested possible influence of testosterone and thyroxin on bursa-spleen relationships during the period of bursal growth and involution.


Growth and development of the fetal Rhesus monkey. VI. Morphometric analysis of the developing lung. Groups of fetal monkeys were studied at 50, 75, 100, 125 and 150 days gestational age, and postnatal monkeys were studied at 175 days gestational age and in adult life (full term gestation is 168 plus or minus 4 days). The ratios between the various tissues of which lung is composed were determined by light and electronmicroscopy. Characteristic changes in ratios were noted at each developmental age. Primitive bronchioles increased from 50 to 75 days, decreased as permanent bronchioles, alveolar ducts and alveoli developed, and were absent after 150 days. Mesenchymal tissue decreased progressively from 50 to 150 days. Alveoli were present at 100 days gestational age; alveolar lumens accounted for approximately 1/2 the volume of peripheral lung by 150 days, and 2/3 the volume of lung in adult animals. By 150 days alveolar epithelial cells could be identified as Type I (membranous) or Type II (granular) on the basis of the characteristic cytoplasmic lamellar inclusion bodies of the latter. The ratios of the Type II/Type I cells were .21-.23 at 150 and 175 days, and fell to approximately half that value in adult lungs.


Compensatory adaptations of skeletal muscle composition to a long-term functional overload. Compensatory hypertrophy of rat plantaris muscle was induced by ablating the synergistic gastrocnemius muscle. The sham-operated contralateral muscle served as a control. Within 5, 30 and 60 days postoperatively, the wet weight of the hypertrophied plantaris was 40, 64, and 109% greater, respectively, than the contralateral control. Two patterns of changing muscle composition emerged with compensatory hypertrophy: (1) an early (less than or equal to 5 days) increase in DNA content (+190%) which resulted in a sharp decline in the wet weight per nucleus ratio (-50%). This coincided with an increase in sarcoplasmic and stromal proteins and a fall in myofibrillar protein concentration. These changes were followed by (2) a secondary increase (30-60 days postoperatively) in the proportions of myofibrillar proteins with a corresponding decline in sarcoplasmic proteins.


Cellular characteristics of skeletal muscle in selected strains of pigs and mice and the unselected controls. Skeletal muscle growth of swine differing in rate of growth and muscularity was studied by analysis of DNA, RNA, and protein in the semitendinosus muscle of fast growing domestic lean pigs (Yorkshire) and the slow-growing feral obese pigs (Ossabaw). Both lean and obese strains were fed ad libitum corn and soybean mean diet containing 14% protein. The pigs were slaughtered at 6 months of age. The Yorkshire pig had significantly greater body and muscle weights (P less than 0.005) Total DNA, RNA, and protein in semitendinosus muscles were significantly greater in the Yorkshire pigs (P less than 0.005). RNA/DNA and protein/DNA ratios were significantly different between the Yorkshire and Ossabaw pigs. These data suggest that the greater muscle growth in the Yorkshire pigs is achieved by greater cell numbers and size. The response of skeletal muscle cells and fiber characteristics to selection was studied in two strains of mice by analysis of DNA, RNA, and histological measurement of muscle fibers. Both strains were fed ad libitum on laboratory rat chow diet. They were sacrificed at 12 months of age. Leg muscle DNA and RNA were significantly greater in the mice selected for rapid growth rate as compared to the control (P less than 0.005 and P less than .10, respectively). Measurements of the semimembranosus muscle reveal that the growth strain had significantly greater muscle weight (P less than .01) and muscle length (P less than 0.005). Histological measurements of the same muscle showed that the growth strain had significantly greater fiber number (P less than 0.005) and larger fiber size (P less than 0.005) than the controls. It would appear that the greater muscle cellularity (DNA) in growth strain mice is accompanied by greater muscle length, fiber number, and fiber diameter.


Oral manifestations of Crohn's disease.

Oral manifestations of Crohn's disease. In a systematic study of 100 patients with Crohn's disease, 100 with ulcerative colitis, and of 100 normal subjects matched for age, sex, and denture status, nine patients with Crohn's disease, two with ulcerative colitis, and one normal control were found to have oral lesions. In Crohn's disease, the macroscopic and histological appearances resembled those encountered elsewhere in the gastrointestinal tract and their incidence was related to the activity of the disorder. The lesions in the other two groups were different macroscopically and histologically. Production of salivary IgA was found to be reduced in Crohn's patients with active bowel disease. It is suggested that the occurrence of oral lesions in patients with Crohn's disease might represent a local immunological reaction to oral antigens.


Estimation of carcinoembryonic antigen in ulcerative colitis with special reference to malignant change. The levels of plasma carcinoembryonic antigen (CEA) were estimated in 59 control subjects attending St Mark's Hospital and in 139 patients with uncomplicated ulcerative colitis. There was little difference in the CEA levels in the two groups. In the colitic patients, the actual CEA values could not be correlated with the age of the patient, the activity of the disease, the extent of bowel involvement, or the length of history. In addition, seven colitic patients with severe dysplastic changes in the rectal mucosa and seven patients with established carcinoma in colitis were studied. With one exception in each group, the CEA levels in these patients were within the range shown by the St Mark's Hospital control population.


Ileal function in patients with untreated adult coeliac disease. A double-lumen perfusion technique has been used to investigate jejunal and ileal absorption of glucose, water, and electrolytes in a group of patients with untreated adult coeliac disease. Correct positioning of the tube was confirmed by measuring the differential jejunal and ileal handling of bicarbonate. Eight control subjects and eight patients with coeliac disease were perfused with an isotonic electrolyte solution containing 50 mM glucose and 25 mM bicarbonate. The group of coeliac patients had impaired jejunal absorption of glucose (P less than 0.001), water (P less than 0.01), sodium (P less than 0.02), and chloride (P greater than 0.05) compared with the control group. In contrast the group of coeliac patients had normal ileal glucose and water absorption and increased ileal sodium (P greater than 0.01) and chloride (P greater than 0.05) absorption compared with the controls. Evidence for ileal adaptation was found in three individual patients who had absorptive values outside 2SD of the normal mean. The results indicate that the distal small intestine in coeliac disease has the ability to adopt to the damage and loss of absorptive capacity in the proximal small intestine.


The effect of intravenous infusions of prostaglandins E-2 and F-2alpha on human gastric function. The effect of intravenous infusions of prostaglandins E-2 and F(-2alpha) at various dose levels on basal, or on maximally or submaximally pentagastrin-stimulated acid secretion, was studied in 40 male subjects. Intraluminal antral pressures were also measured. Prostaglandin F (0.08 mug kg-minus 1 min-minus 1) transiently, but significantly, inhibited submaximal acid output and increased the frequency of antral contractions. Prostaglandin E(2)(0.08 mug kg-minus 1 min-minus 1) inhibited basal acid secretion.


Electrical potential difference, sodium absorption and potassium secretion by the human rectum during carbenoxolone therapy. The transmucosal electrical potential difference (pd) and the sodium and potassium net fluxes were measured in the rectum of subjects taking carbenoxolone. There was a rise in transmucosal pd persisting throughout treatment in all subjects which was accompanied by an increase in sodium absorption and potassium secretion. Comparison of the pd changes produced by carbenoxolone with those due to the mineralocorticoid 9-alpha-fluorocortisol showed that carbenoxolone had about 1/1000th the potency on a weight basis and the two drugs appeared to be additive in their effects. Topical instillation of carbenoxolone into the rectum produced an elevation of pd which persisted for three days. Amiloride and bendrofluazide did not interfere with these actions of carbenoxolone but spironolactone abolished them. One patient who developed fluid retention and hypokalaemia had a rectal pd similar to that of the other patients who had no side effects.


A study of lymph nodes draining colorectal cancer using a two-stage inhibition of leucocyte migration technique. A two-stage technique for leucocyte migration inhibition has been developed which demonstrates the sensitization of lymph node lymphocytes to colorectal tumour extract. The studies have confirmed that some lymph nodes draining colorectal carcinomata contain sensitized lymphocytes. However, the degree of lymphocyte sensitization to tumour extract does not seem greater than that seen in lymph nodes of the small bowel mesentery or of the peripheral blood.


Unexpected natural death of cerebral origin in medicolegal practice. Due to the rapid evolution of vascular lesions it is not surprising that most causes of sudden death of cerebral origin are due to vascular pathology. Of the traumatic causes extradural haemorrhage is a fairly common clinical entity but as a cause of death declining in its frequency. Sources of diagnostic error can be attributed to the fact that not all patients with extradural haematomas have marked external evidence of trauma and a significant number, particularly children and adolescents, show no radiological, clinical or for that matter, post-mortem evidence of a fracture. Subdural haematomas of a chronic variety are usually produced by minor trauma and occur predominantly in the older person. Acute subdural haematomas are most frequently the result of trauma and may be rapidly fatal due to the associated massive cerebral damage. That intracranial aneurysm or angioma may rupture into the subdural space and cause an acute or chronic subdural haematoma, is less widely appreciated. The acute spontaneous arterial subdural haematoma due to the rupture of a cortical vessel, usually one affected by atheroma, into the subdural space is an uncommon entity. It should be looked for specifically in patients with minimal trauma and the clinical picture of an acute subdural haematoma. Subarachnoid haemorrhage due to aneurysmal rupture is still the common cause of unexpected rapid demise in young adults. There is very little evidence that antecedent trauma or exertion play a part as precipitating factors. Centrally placed aneurysms situated at the anterior communicating artery origin or terminal carotid seem to be particularly malignant in their effects. Cause of death is usually massive extrusion of blood into the intracranial cavity with increasing intracranial pressure, compressive haematoma formation and widespread arterial spasm with ischaemic consequences. Whether aneurysmal rupture can be caused by trauma cannot really be satisfactorily resolved. Intracerebral haemorrhage is most commonly due to hypertension but, as in the case of other haematomas, bleeding disorders may also be a cause. Intracerebral haematoma may, however, also result from rupture of micro-angiomata and the brain should be carefully examined for them in the young patient without evidence of hypertension. Hypertensive crises occurring in people on monoamine oxidase inhibitors should also be remembered as a cause of intracerebral haemorrhage.


Unexpected natural death of iatrogenic origin. The paper deals solely with iatrogenic disaster due to the misuse of therapeutic drugs prescribed or unprescribed, and its main purpose is to encourage a high index of suspicion that an unexpected apparently natural death may be iatrogenic due to the medicines administered before death. Toxic effect, side effect and adverse reaction are defined and particular attention is given to adverse effects induced by drug interaction and to the impact of disease and of the extremes of age on the potency of drugs. The deaths under discussion are "biochemical deaths" and as such are difficult to prove at post mortem examination especially if the forensic pathologist has not been made aware of the identity of drugs administered before death. Examples which are apt to create difficulties, particularly those due to drug interaction, are discussed, including oral hypoglycaemics, anticoagulants, anticonvulsants, antidepressants, hypotensives and cardiac glycosides. The solution to the problem is not to refrain from using necessary drugs, but to use them wisely with full awareness of the mechanisms whereby they can become lethal.


Unexpected death of endocrine origin.

Unexpected death of endocrine origin. Diseases of the endocrine glands may be silent or of little apparent consequence for long periods of time, but may nevertheless have an unexpected and acutely fatal termination. Some of these facets are explored in this paper. A full clinical history (including therapy) and thorough autopsy is necessary to exclude the endocrine causes of unexpected deaths.


The evaluation of fat deposits around brain vessels in infants. Perivascular deposits of lipid material around small encephalic vessels in infants had by some authors been regarded as an indication of damage to the vessel walls. It had been presumed that an acute cerebral oedema could be favoured by such a process. Studying the problem in 100 cases of forensic and non-forensic autopsies were found deposits in cells of the adventitial space in the brain of all infants older than 4-5 weeks as well as in those of older infants and adults. Almost exclusively the vessels of the subcortical medulla were concerned. Further histochemical investigations of lipid material in cells of the CNS suggest that the deposited materials is not a preliminary stage of myelination. The deposits seem to be caused by a slight physiological parenchymal degeneration.


Suicide in thailand.

Suicide in thailand. The 581 suicidal cases which occurred in the period 1960-1969, are reviewed from the autopsy reports in the Department of Forensic Medicine, Siriraj Hospital. The following conclusions are drawn: The male: female suicide ratio is 6 : 4; The highest age-group incidence is 20--39 years; Girls predominate among adolescents (0-19 years); By occupation farmers show the highest suicide rate; There is a high incidence among single as well as among married persons; Poisoning is the commonest method of suicide, Parathion being the poison of choice; A suspected predominate cause is emotional instability but among males socioeconomic factors play an important role; There were 11 pregnant cases and 17 attempters in the series studied.


Determination of fluorocarbon 11 and fluorocarbon 12 in post-mortem tissues: a case report. This report describes the death of a teenager due to inhalation of fluorocarbon aerosol propellants and presents a method for the determination of trichlorofluoromethane (fluorocarbon 11) and dichlorodifluoromethane (fluorocarbon 12) in post-mortem samples. The post-mortem blood and tissue levels of these fluorocarbons are also presented. The distribution of fluorocarbon 11 and fluorocarbon 12 is similar to that observed in chloroform deaths.


Detection of firearm discharge residues in blood-stained articles by fluorescence. A quick and sensitive method has been developed for the chemical detection of nitrous derivatives discharged from a firearm. Detection by fluorescence is especially suitable for blood-stained articles such as clothing, which often give confusing results when the conventional methods are used.


Comparative study on the underlying cause and mode of death established prior to and after medicolegal autopsy. A comparative study was made on the underlying cause and mode of death determined in 600 consecutive cases by forensic physicians before and after medicolegal autopsy. All available information including police records, medical documents of decedents and the results of the external medicolegal examination of the corpse were utilized to determine the cause and mode of death before autopsy. The mode of death would have been defined erroneously in 10% of cases and the underlying cause of death in 29.5% of cases if medicolegal autopsy had not been performed. The present results are consistent with previous studies which indicate that the determination of the underlying cause of death is significantly more accurate when an autopsy is performed. They also suggest that in a large number of routine medicolegal cases a similar trend, but at a lower rate, is associated with the determination of the mode of death.


Adaptation and failure of adaptation to extreme natural environments. Although the environmental stresses to which man is subjected on the ground are less than those commonly encountered in aviation or under water, they may still exceed an individual's powers of adaptation. Extremes of temperature, commonly encountered in the Arctic or the tropics, may occur in regions of normally temperate climate and lead to failure of temperature regulation, resulting in hypothermia, frostbite, heat exhaustion, or heat stroke. High mountains impose additional hazards due to high winds and lack of oxygen, and deep mines are dangerous work-places because of high temperature and humidity. Some physiological acclimatization occurs in extreme natural environments and the dangers may be reduced by appropriate clothing, diet and behaviour.


Fatal arrhythmia following deodorant inhalation: case report. With the removal from the general marketplace of volatile hydrocarbons which have been previously abused by "thrill-seekers", new and often unlikely products are now being exploited by those who whish to escape reality. Many of these products have proven harmful. An example of such an unusual product is reported in this case of a sixteen-year-old male who inhaled Arrid Extra-Dry aerosol deodorant and subsequently died following ventricular fibrillation. The only findings at autopsy were cerebral edema, pulmonary edema and generalized visceral congestion.


Papillary clear cell carcinoma of the thyroid gland. A case of an unusual papillary clear cell carcinoma of the thyroid gland is described. The patient expired 17 days after operative biopsy and thyroxine suppression. Special stains were helpful in differentiating renal cortical carcinoma and parathyroid malignant disease from primary papillary clear cell carcinoma of the thyroid. Ultrastructural features of this tumor may relate to the effects of thyroid stimulating hormone as well as the malignant nature of the tumor.


Irregular phenotypic expression of ring chromosomes. 2 patients with 13- and C9-rings are reported. On reviewing the phenotypical features of the published ring carriers and comparing them with our results we do not find any characteristic similarities. This can be explained by cytogenetical and biological findings. We are therefore inclined to reject the existence of clear-cut ring chromosome syndromes.


[Influence of several weeks' treatment of male and female mice with saccharin, cyclamate or cyclohexylamine sulfate on fertility and dominant lethal effects (author's transl)]. The purpose of this investigation was to find out whether long-term treatment of male and female mice with saccharin sodium, sodium cyclamate or cyclohexylamine sulfate, would reduce fertility or induce dominant lethal mutations. Before mating, saccharin sodium or sodium cyclamate were added to the food in a concentration of 1%, while cyclohexylamine sulfate was added in a concentration of 0.11% for at least 10 weeks. This treatment corresponded, in the case of saccharin sodium and sodium cyclamate, to an active substance intake of approx. 2000 mg/kg per day and for cyclohexylamine sulfate to an intake of approx. 200 mg/kg per day (corresponding to approx. 136 mg cyclohexylamine per kilogram per day). These doses affected neither the females nor the males in respect of appearance, behaviour, and weight gain. The doses were also compatible with the normal fertility of the animals. Furthermore, in all cases the treatment did not cause a biologically important increase of pre-implantative and post-implantative losses. The dominant lethal tests did not indicate a mutagenic action of saccharin sodium or sodium cyclamate (1% in the food) and of cyclohexylamine sulfate (0.11% in the food) after 10 weeks' treatment of male and female mice. These results, obtained after long-term treatment, corresponded generally to the findin


In vitro lymphocytic transformation chromosome breakage and cellular damage in Ataxia-Telangiectasia. The lymphocytic transformation in vitro has been studied in 2 cases of ataxia-telangiectasia and compared to that of 2 controls. Significant difference was found between the two groups in the behavior of lymphocytes for two different times of culture. After 48 hrs culturing, important individual variability in RNA synthesis and lower per cent of cells in mitosis was found in the first group. After 120 hrs culturing less important DNA synthesis was found in the first group and about the same per cent of cells in mitosis. After 48 hrs cultures, cellular damage was found in the first group and after 120 hrs cultures, chromosome anomalies were found in the first group.


A homozygote for a serum albumin variant of the slow type. A woman from the Trento district of Northern Italy was found to have albumin of a variant type only. Her parents were first cousins and she had two daughters who were both alloalbuminemic. This is probably the first case of a homozygote for a slow albumin variant and it indicates that individuals with only electrophoretically unusual albumin are physiologically normal.


A contribution to the phenotype distribution of phosphoglucomutase in Czechoslovakia (the district of Ceské Budĕjovice). A population sample of 416 unrelated donors from Ceske Budejovice (southern Bohemia) was investigated for the phenotypes of phosphoglucomutase (PGM).  The calculated frequencies of the alleles PGM1-1 and PGM2-1 0.770 and 0.230, respectively, correspond to the expected frequencies of the phenotypes PGM 1 equals 0.593, PGM 2--1 equals 0.354, and PGM 2 equals 0.0529. No rare phenotype was detected.


Congenital sensori-neural deafness associated with onycho-osteo dystrophy and mental retardation (D.O.O.R. syndrome). A characteristic syndrome is described in which congenital sensori-neural deafness is associated not only with onychodystrophy but also with congenital bony anomalies the most characteristic of which are tri-phalangeal thumbs, bi-phalangeal digits of hands and feet, and dystrophic terminal phalanges of some of the fingers and toes. In addition, there is mental retardation and the dermatoglyphics are characterized by the presence of 10 arches and elevation of the atd angles. The syndrome is inherited as an autosomal recessive. It is suggested that this entity be named the D.O.O.R. Syndrome because of the deafness, onychodystrophy, osteodystrophy and retardation. A similar syndrome without retardation as described by Goodman et al. (1969) appears to be inherited as an autosomal dominant.


Reversal by cyclophosphamide of tolerance in contact sensitization. Tolerance induced by prior feeding with DNCB. Tolerance to DNCB induced by feeding guinea-pigs with the same hapten has been reversed by a single treatment with cyclophosphamide. This is paralleled by a return of the ability of T cells to proliferate in the draining lymph node following sensitization. Certain quantitative differences between this system and that previously described using intravenous DNBSO3 have been revealed. These may indicate some difference between these two mechanisms of tolerance induction.


Interactions between the immunological responses of a thymus-independent antigen (Salmonella adelaide O antigen) with a thymus-dependent antigen (sheep erythrocytes) in the adult bird. The bird's antibody response to a thymus-dependent antigen (sheep erythrocytes) (SRBC) and a thymus-independent antigen (SALMONELLA ADELAIDE O antigen) were characterized: whereas the former proceeded through a brief 19S response to a declining 7S response, the latter failed to switch from 19S TO 7S for several weeks and consisted in repeated excursions of 19S antibodies. When injected intravenously and simultaneously an injection of S. adelaide-killed organisms and SRBC interact, so that the response to the latter fails to switch from 19S TO 7S and consists of repeated excursions of 19S antibodies. The changed character of the SRBC response is interpreted to be due to the relative lack of 7S antibody: passive 7S antibody to S. adelaide O antigen or 7S anti-SRBC produces a negative feedback inhibition of their respective responses, so that only one excursion of 19S antibody is observed. The effect is not, however, symmetrical; the thymus-independent antigen is dominant. Thus, whereas 7S antibody to S. adelaide produces the same negative feedback inhibition on the response to S. adelaide and the response to SRBC (when injected with adlaide), 7S antibody to SRBC inhibits only the response to SRBC and not the response to S. adelaide. These results are discussed relation to current hypotheses of antibody biosynthesis and mechanisms of adjuvant action. They are also discussed in relation to the function of the germinal centres of the spleen which may function to mediate the negative feedback of 7S antibody on the antibody response.


Ultrastructural lesions induced in vitro in guinea-pig spermatozoa by a specific autoantibody (anti-T) and complement. A quantitative ultrastructural study has been carried out on the lesions that are induced in vitro in guinea-pig spermatozoa by the action of auto-antispermatozoa antibodies and complement. The responsibility of three-independent autoantigen-autoantibody systems (S, P and T) has been explored. The only anti-T antibody known to fix complement and to be spermotoxic (T is a membrane-linked autoantigen), caused significant and important lesions, the immunologically specific origin of which was demonstrated. These lesions began a few seconds after complement had been added. The cytoplasmic membrane is first involved, then the acrosomal membranes, and then the acrosomal contents are lysed. The remarkable rapidity of action of complement on the antibody-sensitized target is emphasized. A typical dose-effect curve is obtained with dilutions of anti-T immune sera. Non-C1-fixing anti-S as well as C1-fixing anti-P antibodies (P has been shown to be intra-acrosomal) do not provoke any significant lesions, even in the presence fo complement, as compared to normal and various controls. However, anti-P serum, when added to non-damaging dilutions of anti-T in the presence of complement, was able to provoke significant lesions in the acrosomes. The bearing of these findings on the mechanisms of in vivo lesions is discussed.


Serum factors capable of opsonizing Shigella for phagocytosis by polymorphonuclear neutrophils. Twenty-five Shigella strains were tested for their susceptibility to phagocytosis and killing by polymorphonuclear neutrophils (PMN). The studies identified several serum factors that could participate in opsonization. The strains varied remarkably in their susceptibility to killing when heat-stable opsonins were employed, but all strains were killed when exposed to heat-labile opsonins and PMN. The heat-stable opsonin was shown to be IgG, whereas IgM was ineffective in the absence of complement, and 11S IgA was never effective. Heat labile opsonization required immunoglobulin as well as complement, but IgM was the only immunoglobulin demonstrated to participate in this reaction. The alternative C3 activating pathway is required for efficient heat-labile opsonization of Shigella, but some opsonization also appeared to occur through the C1-C4-C2 pathway of C3 activation.


A comparison of the isoelectrofocusing porperties of antibodies to DNP, DNP-glycylglycylglycine and DNP-p-aminobenzoylglutamate. The charge of heterogeneity of antibodies to DNP-glycylglycylglycine (DNP-Gly-3) and DNP-p-aminobenzoylglutamate (DNP-pABG) has been investigated using preparative liquid isoelectric focusing techniques. The focusing profiles of the two antibody preparations are qualitatively similar, each containing four or five major peaks. The results are also similar to the profiles obtained earlier for DNP antibodies. The binding properties of refocused fractions from the electro-focusing separation of the two DNP-specific antibodies were investigated. Both the unfocused and refocused DNP-pABG antibody fractions were found to be functionally less heterogeneous than the corresponding DNP-Gly-3 fractions, suggesting that the site-filling capacity of the haptens contributed to the observed functional heterogeneity. A marked increase in K0 with increasing pI of the focused antibody fraction was observed for the DNP-pABG antibody preparation. A much smaller increase of K0 with pI was observed for DNP-Gly-3 antibodies and no observed change was found for DNP antibodies. These differences probably reflect the difference in the net charge on the three DNP hapten groups. The isoelectric focusing properties of the separated light and heavy chains from a DNP-antibody preparation and a DNP-pABG antibody preparation were also determined. The light chains in both instances focused as one or two major bands, while the profile of the heavy chain in both cases exhibited five to six major bands. These results are discussed in terms of the model proposed by Haselkorn, Friedman, Givol and Pecht (1974).


Immune complexes in the spleen. The difference between competitive inhibition of immune complex trapping in spleen follicles and inhibition by paratyphoid vaccine. Paratyphoid vaccine injected between 4 days and 3 hours before injection of labelled immune complexes (125-I-labelled BGG-anti-BGG), inhibits follicular trapping of these complexes in the mouse spleen. Inhibition is maximal when paratyphoid vaccine is given 1 day before, almost no label being found in the spleen follicles. No inhibition of follicular trapping of the complexes occurred when paratyphoid vaccine was injected simultaneously with the labelled immune complexes. Competitive inhibition was found when unlabelled immune complexes were given together with labelled immune complexes. Simultaneous injection of mice with paratyphoid vaccine and labelled immune complexes resulted in an additonal form of localization of the labelled immune complexes in the white pulp, heavily labelled clumps also appearing in the periarteriolar lymphocyte sheaths and follicles. The results are discussed in relation to the mechanism of immune complex trapping in spleen follicles.