Variations of neurohypophysial function in normally cycling women.

Using a neurophysin radioimmunoassay, we have studied basal neurohypophysial function in seven normal women. An increase in neurophysin blood levels has been demonstrated during the ovulatory and/or luteal phase as compared to the follicular phase; these variations are related to the changes in the circulating levels of 17beta-estradiol. The data provide additional evidence for a relationship between estrogens and neurohyprophysial function, as previously shown following exogenous administration of estriol and ethinyl estradiol in man.


Further studies on the existence of a sensitizing factor to pressor agents in hypertension.

Further studies are reported on the existence of a sensitizing factor in plasma of hypertensive subjects, which increases the vascular sensitivity to pressor agents when injected iv into nephrectomized rats. Plasma samples from normotensive subjects, patients with malignant hypertension, normotensive dogs, and dogs with experimental renovascular hypertension were fractionated on Bio-Gel P-10 columns after cold acetone precipitation, and on DEAE-cellulose columns eluted with sodium chloride and pH gradients. The effect of the various fractions on the vascular sensitivity to angiotensin was tested utilizing nephrectomized rats. The sensitizing activity was found only in fractions obtained from plasma of hypertensive patients and dogs and it was concentrated primarily in three fractions. Th results suggest that the sensitizing factor is negatively charged at neutral pH and it could be a polypeptide or a small protein.


Effect of insulin-induced hypoglycemia upon plasma renin activity in man.

The effect of insulin-induced hypoglycemia upon plasma renin activity (PRA) was assessed in 4 normal volunteers, 4 adrenalectomized patients and 10 patients with various pituitary hormone deficiences. Significant increases in PRA were observed in all three groups. The PRA responses to hypoglcemia could be blocked by propranolol, and appeared to be potentiated by theophyline. It is concluded that sympathetic reflex stimulation, not adrenal-dependent and not pituitary-dependent, is the major mechanism for this phenomenon in man and that this adrenergic effect may be mediated by cyclic AMP.


A natriuretic principle derived from kidney tissue of volume-expanded rats;.

Homogenates of kidneys from hydropenic and volume-expanded rats were subjected to gel filtration with Sephadex G-25. A fraction of the eluate coincident with the fourth UV peak was injected into the aorta of rats with one kidney excluded. A fraction eluting before the albumin peak was utilized as a control. Significant natriuresis and diuresis were observed after infusion of the fraction obtained from volume-expanded kidneys but not after infusion of the fraction from hydropenic kidneys or the control fraction. The natriuresis occurred in in the absence of changes in mean blood pressure, hematocrit, plasma sodium and potassium, glomerular filtration rate, and potassium excretion. The response was apparent immediately after infusion and persisted for up to 150 min. These results verify the existence of a low molecular weight natriuretic substance which may be preferentially bound to the  kidney after its volume-stimulated release into the circulation.


Elevated serum thyroglobulin. A marker of metastases in differentiated thyroid carcinomas.

The presence of human thyroglobulin (HTg) in serum of patients was identical by immunological criteria to the serum standard used in the radioimmunoassay. The serum thyroglobulin levels in untreated patients with differentiated thyroid carcinoma ranged from 22.0 to 445.0 ng/ml with a mean of 144.3 +/- 46.5 ng/ml (SEM) (n = 10). The mean serum thyroglobulin measured postoperatively in seven of these patients was 6.4 +/- 1.5 ng/ml, not statistacally different from the mean level of 5.1 +/- 0.49 ng/ml (range 0-20.7 ng/ml) observed in 71 out of 95 control subjects with detectable HTg levels. By contrast serum HTg levels were normal or undetectable in subjects with medullary carcinoma of the thyroid. HTg levels were within normal limits in sera of patients who had previously undergone successful therapy for a differentiated thyroid carcinoma and in whom no metastases could be documented. The mean level for this group was 4.9 +/- 0.51 ng/ml (n = 43). In contrast, patients with documented metastases had a mean serum thyroglobulin level of 464.9 +/- 155.6 ng/ml (n = 6). The data support the thesis that in differentiated thyroid carcinoma serum thyroglobulin levels are elevated when metastases develop after initial treatment. It is proposed that the measurement of thyroglobulin in the serum represents a simple and valuable adjunct in the posttreatment follow-up of patients with differentiated thyroid cancer.


Influence of acute myocardial depression on left ventricular stiffness and its elastic and viscous components.

The influence of acute myocardial depression on ventricular stiffness and on its elastic and viscous components was studied in 19 dogs. After the animals were placed on cardiopulmonary bypass, stiffness was measured by sinusoidally injecting volume changes of 0.5 ml (deltaV) at 22 Hz into paced, isovolumically (deltaP) of the sinusoidal pressure response. Stiffness was linearly related to pressure (P) throughout the cardiac cycle, so that deltaP/delta V = alpha P + beta, where alpha and beta are constants. Myocardial depression was induced in one of three different ways: by coronary artery ligation, by administration of propranolol (Inderal), or by administration of pentobarbital. All three interventions caused significant increases in the slope, alpha, of the stiffness-pressure relationship, while the intercept, beta, remained unchanged. Release of the coronary occlusion or administration of acetylstrophantidin partially reversed depression and the change in alpha; Approximation of the mechanical nature of the left ventricle in terms of a linear second-order mechanical system permitted the division of stiffness into its elastic and viscous components. Like total stiffness, both the elastic and the viscous components were linearly related to ventricular pressure. Elastic stiffness was not changed, but the slope of the line relating viscous stiffness to pressure was significantly increased during ischemic depression, indicating that a change in viscosity was primarily responsible for the increase in total ventricular stiffness.


The influence of salt intake on the metabolic acidosis of chronic renal failure;.

The influence of dietary salt on the levels of plasma bicarbonate and on the characteristics of bicarbonate reabsorption was studied in experimental chronic renal failure. Chronic renal failure was produced in rats by sequential partial nephrectomies. The control group received a diet constant in salt content throughout the progression of renal failure; the other group (PRNa), at each stage of renal failure, received salt intake reduced in direct proportion to the fall in glomerular filtration rate (GFR). In the steady state, the quantities of urinary sodium closely approximated intake in obth groups of animals. The adaptive increased natriuresis per nephron exhibited by the control animals was prevented in the PRNa animals. The PRNa group had (a) higher plasma bicarbonate levels, (b) increased bicarbonate thresholds, and (c) increased maximal tubular reabsorptive capacity for bicarbonate. As renal failure progresses, dietary salt can become a determining factor of the levels at which plasma bicarbonate is maintained. Proportional reduction of dietary salt results in bicarbonate conservation in rats with experimental progressive renal failure.


Colonic electrolyte transport in health and in congenital chloride diarrhea.

Congenital chloride diarrhea (CCD) is a rare autosomal recessive disorder, characterized by watery stools with C1- concentration around 150 meq/liter. We have perfused the colon of three patients and their three healthy siblings with different salt solutions containing 36C1- to determine the nature of the colonic defect in CCD. In the controls, net absorption of Na+ and C1- occurred against steep concentration gradients. The influx (lumen-to-plasms flux) of C1- was twice the effux. Omission of HCO3- from the perfusate caused a clear decrease in C1- efflux which suggests a coupling of C1- effux to HCO3- influx. In CCD, net Na+ absorption occurred normally when HCO3- was present in the lumen. However, Na+ absorption was always impaired when the luminal contents were acid, a situation that prevails in CCD. Net K+ secretion was clearly increased. Both influx and efflux of C1- were practically absent. Only slight net secretion occurred along a steep gradient. Net appearance of HCO3- was not observed, in contrast to controls. These findings and earlier studies of ileal function in CCD are best explained by a defect in the C1-/HCO3- exchange mechanism, which operates in both directions in the normal ileum and colon.


The loss of bone mineral with aging and its relationship to risk of fracture.

Longitudinal studies have shown that individuals lose bone mineral at unequal rates with aging. It has been postulated that individuals with the more rapid rates of loss constitute a separate population having an increased risk for developing fractures, i.e., osteoporosis. To examine this postulate, we made a search for a separate population of elderly women using a precise and objective measurement technique of bone mineral, photon absorptiometry. Bone mineral content (BMC) was measured in the radius of 571 Caucasian females who were age 50 or older. It was found that BMC values adjusted for width had a normal distribution in all decades and the variation in BMC values did not increase with age. Subjects with vertebral fractures (n = 108) were estimated to be losing bone mineral at the same rate as those without vertebral fractures (n= 161). Thus evidence for a separate population of rapid losers of bone mineral was not found. Reconciliation of longitudinal studies which show unequal rates of loss with the present population survey, in which evidence for unequal rates was not found, would require that (a) the rate of loss of bone mineral for an individual is not constant and/or (b) the rate of mineral loss is proportional to the amount of mineral present at maturity. The incidence of vertebral fractures was inversely proportional to BMC values. In a group of 278 women followed for 470 subject-yr, the incidence of all fractures during the study (n = 31) was also inversely proportional to BMC. These data suggest that the BMC values of osteoporotics would be at the lower end of normally distributed values for the population.


Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

The ability of antibiotics to prevent Streptococcus sanguis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.


The effect of potassium loading on sodium excretion and plasma renin activity in Addisonian man.

Potassium has been shown to suppress plasma renin activity (PRA). This study was designed to study the role of increased aldosterone production in the mediation of such a response. Five patients with adrenal insufficiency were placed on a diet of 60 meq potassium and 100-150 meq of sodium while receiving a constant amount of cortisone acetate and Florinef. Upright PRA was determined each day for 2-3 days in the control period and then for 3-4 days after potassium intake had been increased to 200-300 meq/day. Potassium loading induced a natriuresis. Hence, patients were either sodium replaced (six studies in four patients) or allowed to become sodium depleted (three patients). Potassium loading without replacement was associated with a decrease in weight, negative sodium balance, hyperkalemia, and a positive potassium balance. PRA rose during the experimental period. Potassium loading with sodium replacement was associated with little change in weight or sodium balance. Hyperkalemia and positive potassium balance were present to the same degree as found in the studies without sodium replacement. When all PRA values are considered (both morning and evening values) there was no significant change with potassium loading (+ 1.31 ng/ml per h; range + 6.9 to -2.0). We conclude that hyperkalemia or a positive potassium balance did not suppress PRA in Addisonian man in these studies when sodium balance was maintained, nor did it prevent a rise in PRA when sodium balance was negative.


Influence of sympathetic stimulation and vasoactive substances on the canine pulmonary veins.

The contribution of the intrapulmonary lobar veins to the increase in pulmonary vascular resistance in response to sympathetic stimulation was studied under conditions of controlled blood flow in the anesthetized dog in which vascular pressures were measured simultaneously in the perfused lobar artery, an intrapulmonary lobar vein 2-3 mm in diameter and in the left atrium. Stimulation of the stellate ganglia at 3, 10, and 30 cycles/s increased pressure in the lobar artery and small vein in a stimulus-related manner but decreased pressure in the left atrium. Injection of norepinephrine into the perfused lobar artery also increased pressure in the lobar artery and small vein but decreased pressure in the left atrium. The increase in lobar arterial and venous pressure in response to either injected norepinephrine or to nerve stimulation was antagonized by an alpha receptor blocking agent. The rise in pressure in both labor artery and small vein with nerve stimulation but not administered norepinephrine was inhibited by an adrenergic nerve terminal blocking agent. The results suggest that under conditions of steady flow, sympathetic nerve stimulation increases the resistance to flow in the lung by constricting pulmonary veins and vessels upstream to the small veins, and that at each stimulus-frequency studied approximately 50% of the total increase in resistance may be due to venoconstriction. It is concluded that the increase in resistance to flow in the lung in response to nerve stimulation is thre result of activation of alpha adrenergic receptors by norephinephrine liberated from adrenergic nerve terminals in venous segments and in vessels upstream to samll veins, presumed to be small arteries.


Action of cholecystokinin and cholinergic agents on calcium transport in isolated pancreatic acinar cells.

COOH-terminal octapeptide of cholecystokinin (CCK-octapeptide) and the cholinergic agent carbamylcholine each produced a fourfold stimulation of calcium outflux in guinea pig isolated pancreatic acinar cells. Neither agent altered calcium influx. Stimulation of calcium outflux was rapid and specific, was abolished by reducing the incubation temperature to 4 degrees C, and was a saturable function of the secretagogue concentration. The concentrations of CCK-octapeptide and carbamylcholine that produced half-maximal stimulation of calcium outflux were 3.1 x 10(-10) M and 4.9 x 10(-5) M, respectively. The cholinergic antagonist antropine competitively inhibited carbamylcholine stimulation of calcium outflux but did not alter stimulation produced by CCK-octapeptide. Stimulation of calcium outflux by maximal concentrations of carbamycholine plus CCK-octapeptide was the same as that produced by a maximal concentration of either agent alone.Calcium outflux became refractory to stimulation by secretagogues, and incubation with either CCK-ostapeptide or carbamylcholine produced a refractoriness to both agents. The relative potencies with CCK and its related fragments stimulated calcium outflux were CCK-octapeptide greater than heptapeptide greater than CCK greater than hexapeptide = gastrin. Secretin, glucagon, and vasoactive intestinal peptide, at concentrations as high as 10(-5) M, failed to alter calcium outflux and did not affect stimulation by CCK-octapeptide or  by carbamycholine.


Clarification of the site of action of chlorothiazide in the rat nephron.

The saluretic effect of the thiazide diuretics has been attributed to inhibition of sodium reabsorption in the distal nephron of the kidney. Recent micropuncture studies have shown, however, that chlorothiazide administration can also inhibit sodium reabsorption in the proximal convolution. To clarify the site of the saluretic effect of chlorothiazide, these micropuncture studies examined the effect of chlorothiazide on chloride transport in the nephron. The effect of chlorothiazide on chloride transport was studied because chlorothiazide's effectiveness as a saluretic is largely due to its ability to enhance sodium chloride excretion; if only changes in sodium transport are examined, it would be then difficult to determine if sodium as bicarbonate or as chloride is affected, since chlorothiazide can inhibit carbonic anhydrase. One group of rats was studied before and after 15 mg/kg per h chlorothiazide. For comparison, another group of rats was studied before and after 2 mg/kg per h benzolamide, a carbonic anhydrase inhibitor. Fractional chloride delivery from the proximal tubule was similarly increased in both groups from 59.4 to 71.0% by chlorothiazide administration, Pless than 0.0001, and from 54.3 to 68.2% by benzolamide administration, P less than 0.001. The increased delivery very of chloride from the proximal tubule was largely reabsorbed before the early distal tubule as fractional chloride delivery to this site increased only from 5.08 to 7.40% after chlorothiazide administration, P less than 0.001, and from 4.50 to 6.29% after benzolamide administration, P less than 0.01. Benzolamide had no effect on chloride reabsorption in the distal convoluted tubule. However, chlorothiazide administration resulted in a marked decrease in distal tubular chloride reabsorption, the fraction of filtered chloride present at the late distal tubule incresing from 1.24 to 6.25%, P less than 0.001. Fractional chloride excretion in the urine increased from 0.29 to 3.44%, P less than 0.001, after chlorothiazide, but did not change after benzolamide. The influence of chlorothiazide on proximal chloride transport presumably is related to its ability to inhibit renal carbonic anhydrase. However, it is not the effect of chlorothiazide in the proximal convolution but rather its effect in the distal convoluted tubule which is primarily responsible for its ability to be an effective saliuretic.


NaHCO3 and NaC1 tolerance in chronic renal failure.

In patients with chronic renal failure, NaHCO3 therapy may correct or prevent acidemia. It has been proposed that the NaHCO3 required will not result in clinically significant Na retention comparable to that from similar increases in NaC1 intake. In each of ten patients with chronic renal failure, creatinine clearance (Ccr) range 2.5-16.8 ml/min, on an estimated 10-meq Na and C1 diet, electrolyte excretion was compared on NaHCO3 vs NaC1 supplements of 200 meq/day. Periods of NaHCO3 and NaC1 (in alternate order for successive patients) lasted 4 days, separated by reequilibration to base-line weight. Mean +/- SEM excretion (ex) of Na, C1, and HCO3 and deltaCcr and deltaweight (day  4-1) are compared below for the 4th day of NaC1 vs. NaHCO3 intake. Mean Ccr +/-SEM on day 4 of NaC1 and NaHCO3 were 10.8 +/-1.6 and 9.0 +/-1.4 ml/min, respectively (P less than 0.02). Mean systolic blood pressure (but not diastolic) increased significantly on NaC1 (P less than 0.05). No significant blood pressure changes were seen on NaHCO3. Net positive HCO3 balance occurred on NaHCO3 as indicated above and reflected a rise in mean serum HCO3 from 19 to 30 meq/liter (day 1 vs. 4) (P less than 0.01). Mechanisms for the greater excretion of Na on NaHCO3 may relate to C1 wasting as noted above on low C1 intake and limited HCO3 reabsorptive capacity. Thus, Na excretion by day 4 was greater on NaHCO3 than on NaHCO3 did Na excretion near intake (210 meq/day).


Evidence for an in vivo antagonism between vasopressin and prostaglandin in the mammalian kidney.

These studies were undertaken to examine whether an antagonism between vasopressin and prostaglandin occurs in vivo in the mammalian kidney. All experiments were performed in steroid-replaced hypophysectonized dogs undergoing a water diuresis. In the first group of studied the effect of two consecutive intravenous doses (100 mU) of vasopressin was examined. The second dose of vasopressin was preceded by an injection of the carrier solution for solubilizing indomethacin or neclofenamate. No enhancement of the antidiuretic effect of the second dose of vasopressin was observed as urinary osmolality (Uosm) increased from 92 +/- 5 to 252 +/- 18 mosmol/kg H2O (P less than 0.0001) after the first dose and from 109 +/- 8 to 209 +/- 10 mosmol/kg H2O (P less than 0.001) after the second dose of vasopressin. In another group of studies the second dose of vasopressin was preceded by the administration of a potent inhibitor of prostaglandin synthesis, indomethacin (2 mg/kg). The Uosm increased from 93 +/- 9 to 244 +/- 33 mosmol/kg H2O (P less than 0.001) after the first dose of vasopressin, but after the second dose of vasopressin the Uosm increased to a significantly greater degree from 106 +/- 14 to 702 +/- 69 mosmol/kg H2O (P less than 0.001). In a third group of studies the antidiuretic effect of the same 100-mU dose of vasopressin was examined before and after the administration of meclofenamate (2 mg/kg), an inhibitor of prostaglandin synthesis which is chemically dissimilar from indomethacin. Uosm increased from 83+/-7 to 216+/-16 mosmol/kg H2O (P less than 0.001) after the first dose and from 101 +/- 8 to 734 +/- 86 mosomol/kg H2O (P less than 0.001) after the second dose of vasopressin. As in the indomethacin studies this enhancement in the antidiuretic effects of vasopressin after inhibition of prostaglanding synthesis was highly significant (P less than 0.001). These results therefore implicate a physiological role of prostaglandin in modulating the hydroosmotic effect of vasopressin in the mammalian kidney.


Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs.

A comparison study of several vasoconstrictor and vasodilator agents was conducted measuring changes in intestinal blood flow and oxygen consumption during 10-min periods of intra-arterial infusion. Blood flow was measured in a branch of the superior mesenteric artery of anesthetized dogs with an electromagnetic blood flow meter, and the arteriovenous oxygen content difference across the gut segment was determined photometrically. Vasopressin (4 x 10(-3) and 7x 10(-4) U/kg-min) diminished blood flow 60 and 28% and reduced oxygen consumption 54 and 22%, respectively (all P less than 0.001). In a dose which did not lower blood flow, vasopressin still caused a decline in oxygen consumption (P less than 0.01). Epinephrine (5 x 10(-2) mug/kg-min) decreased blood flow 19% (P less than 0.001) but did not reduce oxygen consumption. After beta-adrenergic blockade, however, the same dose of epinephrine decreased blood flow 41% and oxygen consumption 33% (both P less than 0.001). Responses to angiotension II, calcium chloride, and prostaglandin F2alpha resembled effects of vasopressin rather than those of epinephrine, namely decreased blood flow and decreased oxygen consumption. The vasodilator agents, prostaglandin E1, is isoproterenol, and histamine, increased (P less than 0.001) both blood flow (130, 80, and 98%, respectively) and oxygen consumption (98, 64, and 70%, respectively). Vasopressin, angiotensin II, calcium chloride, and prostaglandin F2alpha appear to contract arteriolar and precapillary sphincteric smooth muscle indiscriminately to evoke both intestinal ischemia and hypoxia. Epinephrine is the exceptional constrictor in this case, producing diminished blood flow without a reduction in oxygen uptake.


Free DNA in serum and plasma from normal adults.

Circulating DNA has been associated with several human disorders, including the nephritis of systemic lupus erythematosus (SLE), in which it is thought to play an etiological role. However, it remains unclear whether its appearance in the circulation is truly pathological. Several reports, each generally based on a single assay method, have disagreed as to whether DNA may circulate in normals. Some, but not all, of this disagreement may be explained by the recently described appearance of DNA in serum, but not plasma, apparently as the result of release from leukocytes in vitro. In the present report an attempt is made to clarify this problem. Normal plasma and serum samples were examined by four assays for DNA that were newly modified to enhance their specificity and/or sensitivity. Plasma DNA was undetectable by all four methods, the most sensitive of which could detect 0.05 mug/ml of native DNA (nDNA) or 0.1 mug/ml of single-stranded DNA (ssDNA). Serum DNA was present in 14 of 16 samples tested in variable concentrations with an estimated mean of 1.9 mug/ml. It is concluded that the appearance of DNA in adult human plasma is a pathological event. Presumably, previous reports describing detection of DNA in normal plasma were based on the measurement of non-DNAase-sensitive interfering substance. Furthermore, it is emphasized that the use of serum in studies dependent on sensitive assays for DNA (or anti-DNA antibody) introduces an ambiguity that may be avoided by substitution of carefully collected plasma for serum.


Anaemic crisis in sickle cell disease.

Sixteen episodes of acute anaemia necessitating urgent blood transfusion have been investigated in 13 children with sickle cell anaemia. In five out of seven episodes there was evidence of increased haemolysis while in 10 out of 16 episodes a profound fall in reticulocyte count indicated marrow erythroid cell failure. Cold agglutinins active at room temperature were detected in 13 episodes, and anti-I specificity was demonstrated in 11. Warmed blood of homologous ABO and Rhesus groups was administered without complication despite difficulty with cross-matching. The exacerbation of anaemia was not due to folate lack, glucose-6-phosphate dehydrogenase deficiency or splenic sequestration, and an infectious agent appeared responsible. The degree of anaemia in homozygous sickle cell disease is usually constant during asymptomatic periods. An episode of sudden profound anaemia (anaemic crisis) may, however, result from marrow hypoplasia, an exacerbation of haemolysis, splenic sequestration, or folate deficiency.


Two cases of sodium azide poisoning by accidental ingestion of Isoton.

Accidental ingestion of sodium azide in 0-1% solution by a patient and a laboratory technician in a haematological laboratory has demonstrated that very small quantities of sodium azide can give rise to toxic symptoms and that Isoton should be handled with care.


Thrombolytic therapy and myocardial infarction.

Examination of 27 hearts from patients treated by streptokinase following myocardial infarction showed one major histopathological difference from controls, the presence of massive interstitial haemorrhage into the necrotic tissue in some cases. This change is presumably related to the re-establishment of the circulation to infarcted areas.


Pulmonary oedema at necropsy: a combined pathological and radiological method of study.

Fixation of lungs at necropsy by inflation with formaldehyde vapour was used in a combined radiological and pathological study of pulmonary oedema. Pulmonary oedema was found in 79% of lungs examined. The earliest phases affect the interstitial tissue with oedematous connective tissue planes and distension of pulmonary lymphatics. These changes may be associated with reduction in the compliance of the lung. Alveolar filling is a late stage in the accumulation of oedema fluid in the lungs.


Intestinal polyps in the Nigerian African.

Intestinal polyps appear to be relatively rare in the African including Nigerians, South African Bantus, and Ugandans. Only 40 histologically confirmed cases were encountered over a period of ten years. Analysis of these cases reveals a preponderance (60%) of the non-neoplastic juvenile type of polyp. Neoplastic polyps were not encountered in any female patient. The mean ages of the patients are much lower than what has been observed in Caucasians inhabiting developed and industrialized countries. It is felt that there is probably a common or related aetiological agent for neoplastic intestinal polyps and carcinoma because the frequency of intestinal carcinoma appears to be relatively low in areas with a low frequency of neoplastic polyps.


Reduced lymphocyte transformation in early cancer of the breast.

The cell mediated immune response has been measured in vitro by lymphocyte transformation in 53 patients with malignant tumours of the breast and an equal number of patients in the same age group operated upon for benign tumours. The response to phytohaemagglutinin (PHA) was reduced in the patients with malignant tumours when the lymphocytes were grown either in the patient's plasma or in autologous plasma. This was observed when the response was measured both by the uptake of radioactive DNA precursor and by autoradiography. Reduced lymphocyte transformation was present even very early in the disease and certainly preoperatively. The reduction appeared to be even more marked in the advanced cases. An interesting finding was that the plasma from cancer patients contained a factor which reduced the PHA transformation of lymphocytes from a healthy donor.


The detection of specific IgM antibodies following infection with rubella virus.

A gel filtration technique using Sephadex G-200 has been used for the detection of specific IgM in sera from (a) 45 cases of clinical rubella in which diagnostic rises of rubella haemagglutination-inhibiting (HAI) antibody could be demonstrated; (b) 70 cases with clinical evidence of rubella in which a rising titre could not be demonstrated because the first serum sample already had high titre HAI antibodies; and (c) 100 patients in whom rubella was not suspected. The results indicate that the high specificity and sensitivity of the method described make it an appropriate technique for use in the routine diagnosis of acquired rubella.


Antibiotic-disc tests for rapid identification of non-sporing anaerobes.

The sensitivity patterns to a number of antibiotic-impregnated discs of 126 strains of Gram-negative anaerobes and 36 strains of Gram-positive non-sporing anaerobes from various sources have been examined. The sensitivity patterns shown by Bacteroids fragilis and Bacteroides melaninogenicus were useful for the rapid identification of these organisms. Consistent and useful sensitivity patterns were not shown by the Gram-positive anaerobes.


A clinico-pathological study of vulval dermatoses.

A long-term review of 108 women suffering from various forms of vulval dermatosis is described and a detailed analysis of those with chronic hypertrophic vulvitis, lichen sclerosus et atrophicus, and neurodermatitis is made. One case of neurodermatitis and two cases of lichen sclerosus progressed to carcinoma but no case of chronic hypertrophic vulvitis became malignant. It is possible that vulval dermatoses occur more commonly in the nulliparous than in the parous women and there is a slight preponderance of women who are blood group A. It is suggested that the term "leukoplakia" should be abandoned and that vulval lesions should be described in precise and meaningful histological terms.


An experimental comparison of Thiol broth with Brewer's thioglycollate for anaerobic blood cultures.

In a series of simulated blood culture experiments, small inocula of eight different strains of Bacteroides and five strains of anaerobic cocci were added to Difco Thiol broth and Southern Group Brewer's thioglycollate. Both methods enabled all of the strains to be isolated after one to three days' incubation, with the exception of Bacteroides melaninogenicus, and most strains to survive after one week. B. melaninogenicus grew more quickly in Difco Thiol broth than in Southern Group Brewer's whereas three strains of anaerobic cocci were isolated first from Southern Group Brewer's. Difco Thiol broth appears to be a satisfactory alternative to Southern Group Brewer's for the isolation of non-sporing anaerobes likely to be found in the blood.


Extraction of serum vitamin B12 for radio-isotopic and Lactobacillus leichmannii assay.

The protein precipitates discarded during the extraction process of the Lactobacillus leichmannii vitamin B12 assay have been shown to contain significant amounts of vitamin B12. This loss of vitamin B12 provide a satisfactory explanation for many of the descrepancies between the serum vitamin B12 values obtained by the L. leichmannii method and the radio-isotopic method of Raven et al (1969). It is possible to produce lower results by the method of Raven et al (1969)by incorporating into that method the L. leichmannii extraction process; it is also possible to produce higher results by the L. leichmannii method using a papain extraction process.


An automated immunoradiometric assay for ferritin.

A semi-automated method for the immunoradiometric assay of ferritin has been developed. Results obtained with serum samples show excellent correlation between this method and the previously described assay. A further useful reduction in the assay time may be achieved by incubating for 3 hours at 37 degrees C instead of 24 hours at 4 degrees C.


Injury and repair of tracheobronchial cartilage following accidental exposure to ehtyleneimine.

A fatal case following ehtyleneimine inhalation is described. Profound destructive effects on tracheobronchial cartilage were found at necropsy after an interval of apparent recovery from early phases of poisoning. The pathogenesis of these cartilaginous changes is discussed. It is proposed that they may have been due to proteases liberated from liberated from mucosal granulation tissue.


Myocardial lysis in acute rheumatic fever followed by regeneration of cardiac muscle and origin of Aschoff bodies.

In acute rheumatic heart disease, lysis of cardiac muscle fibres with or without retention of sarcolemma is found to be the most damaging feature in many cases. In deeper myocardium the cellular lysis often forms anastomosing clefts or sinus-like spaces between surviving muscle bundles and in the outer portion of myocardium cellular lysis may leave the sarcolemma more or less intact. From lysing cardiac muscle fibres there arise dedifferentiated cells with remarkable potentiality for regeneration. For the origin of these dedifferentiated cells, which are often indistinguishable from lymphocytes, no mitosis is seen in cardiac muscle cells. The successive stages of development of muscle cell from these dedifferentiated cells within the remaining or newly formed sarcolemma have been observed in this study. This study infers that the increased number of fibrous septa, when seen, denotes the tracks of previous muscle degeneration and subsequent replacement of it with incomplete muscle regeneration and fibrous tissue formation. In an area of muscle lysis the origin of Aschoff bodies from these dedifferentiated cells has been followed. Ashoff bodies arising in this was behave as an abortive and atypical growth of muscle fibres in a nodular fashion specific to rheumatic fever.


Bilateral fibrosarcoma of the epididymis.

The tenth case of primary fibrosarcoma of the epididymis is reported. Contrary to most previous cases, excision biopsy was followed by a lengthy tumour-free period, and a unique feature was bilateral epididymal recurrence.


Evaluation and utilization of a kinetic enzyme direct measuring photometer.

We have recently utilized a prototype model of the Beckman Enzyme Activity Analyzer System-TR in our laboratory measuring various serum enzyme activities which include: alkaline phosphatase (ALP), E.C.3.1.3.1; creatine kinase (CK), E.C.2.7.3.2; hydroxybutyrate dehydrogenase (HBD), E.C.1.1.1.30; lactate dehydrogenase (LD), E.C.1.1.1.27; aspartate transaminase (AST), E.C.2.6.1.1; and alanine transaminase (ALT), E.C.2.6.1.2. Precision was found to be good. Sample activities could be measured as high as 1000 IU/1. The carryover studies fell within 2 SD of the means of the enzyme control studies. Coefficients of variation for ALP and CK were in the ranges of 0-40-2-14% and 0-52-4-30%, respectively. Correlation studies were done with GemSAEC and Gilford 300 N Spectrophotometer and the results were accurate, precise, and reproducible.


Failure of indomethacin and warfarin to interact in normal human volunteers.

In young, normal, male Caucasian volunteers, two different double-blind, placebo-controlled, randomized studies were performed to determine whether indomethacin interacts in a clinically significant fashion with warfarin. In the first study, stabilized hypoprothrombinemia was achieved by daily oral warfarin administration for at least 11 days; then indomethacin was administered concurrently with warfarin for five more days. During this five-day period failure of indomethacin to alter the degree of hypoprothhrombinemia induced by warfarin indicated that indomethacin does not interact with warfarin in vivo in a clinically significant fashion. A similar conclusion was drawn from results of the second experiment, in which plasma warfarin concentrations and prothrombin times were measured after a single oral dose of warfarin administered both before and after ten consecutive days of oral indomethacin administration. Thus, these studies suggest that warfarin may be given to patients receiving indomethacin and indomethacin may be administered to patients on warfarin without intensification or diminution of the normally expected hypoprothrombinemie effects of the dose of warfarin in that individual.


A methodological study of some factors influencing the reporting of symptoms.

The spontaneous occurrence of symptoms that are often regarded as adverse drug reactions was studied by means of open questionnaires or by a 38-item checklist of symptoms. Of the 416 respondents who returned an analyzable questionnaire, only 233 (56 per cent) were healthy (defined as having had no illness and/or having taken no medication in the previous three days). Using the open questionnaires, one or more symptoms were reported by 15 per cent of healthy persons (N equals 155) and by 69 per cent of a group of 118 persons who had been ill and/or who had taken medication in the previous three days. In contrast, using the checklist questionnaires 82 per cent of healthy persons (N equals 78) and 97 percent of persons who had been ill and/or who had taken medication in the previous three days (N equals 65) reported one or more symptoms. The total number of symptoms reported by any one person was three with the open questionnaire and 22 with the checklist. In addition, a greater severity of symptoms was associated with the open questionnaire. Sex, educational level, or presence or absence of previous exposure to clinical trials did not influence the nature and incidence of symptoms reported. However, the severity of symptoms reported was significantly different for the latter two factors. Differences in the frequency with which certain symptoms were reported and the relevance of these and other observations to the design of clinical trial record forms are discussed.


The effect of lidocaine on peripheral hemodynamics.

Lidocaine was given in increasing step-wise dose concentrations of 1, 2, 3, 4, and 5 mg/minute and the resulting serum concentrations correlated with the effect of this agent on the peripheral vasculature of seven patients. Lidocaine infusion causes an immediate sustained increase in mean calf venous capacitance but little effect on mean diastolic blood pressure. In high concentration levels this agent causes an increase in mean calf blood flow and systolic blood pressure. Its effect on calf vascular resistance is variable, but there is a tendency to reduce resistance, particularly at a high concentration level. The effect of lidocaine infusion rate on serum lidocaine levels was such that the greater the infusion rate, the higher the resultant serum lidocaine levels.


Assessment of aspirin absorption rate from urinary excretion rate measurements.

It is shown on the basis of pharmacokinetic simulations and experimental data that adequate evaluation of aspirin dosage forms with different absorption rates by urinary excretion measurements in man requires that such measurements be made during the first hour after drug administration. Measurements made only after 3 hours are totally inadequate for that purpose. An assessment of the completeness of absorption obviously does not require serial measurements but needs only a determination of the total amount excreted.


A controlled comparison of doxepin h.s. and doxepin q.i.d.

A controlled double-blind study of 40 depressed psychiatric outpatients who received doxepin either q.i.d. or h.s. showed that doxepin may be administered h.s. without loss of efficacy or increase in side effects. The patients who received doxepin h.s. felt significantly better rested in the morning than the patients who received doxepin in divided doses.


Some aspects of synaptogenesis in the spinal cord of the chick embryo: a quantitative electron microscopic study.

We have quantitatively examined the development of synapses in the ventral part of the lumbar spinal cord of the chick from embryonic day 4 until adulthood. The first synapses occur on day 4 and are of the axo-dendritic type; they are invariably located adjacent to the border between the intermediate and marginal zones. Initially there are more synapses in the presumptive white matter than in the motoneuron neuropil, but this trend is later reversed; however, we found numerous axo-dendritic synapses throughout much of the ventrolateral white matter even in the adult stage. The first axo-dendritic synapses always contain spherical synaptic vesicles and have symmetric membrane specilizations. By day 7 a few of these synapses were found to have mixed populations of spherical and flattened vesicles and asymmetric membrane specilizations. After hatching there are still considerably more axo-dendritic synapses with symmetric membrane specializations. Axo-somatic synapses were first found on embryonic day 6 and were typically located on motoneurons lying adjacent to the marginal zone. These axo-somatic synapses contain a few spherical synaptic vesicles and have symmetric membrane densities. Flattened synaptic vesicles were first found on day 10 and increased throughout development. Although a few axo-somatic synapses with asymmetric membrane specializations were found at practically all stages, the symmetric type was always in the majority. An attempt was made to relate these observations with physiological, behavioral and neuroembryological findings from birds and other forms. For example, the fact that axo-dendritic synapses always appear prior to axo-somatic contacts would seem to rule out the role of somatic synapsesin the initial induction of dendritic growth in the spinal cord.


An estimate of the number of cells arising by division in mouse cerebral hemispheres from age one to 12 months: an autoradiographic study of DNA synthesis.

Male CBA strain mice aged 1, 2, 4, 6, 8 and 12 months were injected with 5 muCi of 6-H3-thymidine per gm body weight and killed two hours after the injection. Incorporation of the isotope, as a measure of DNA synthesis and cell division, was studied in the cerebral cortex and corpus callosum by light-microscope autoradiography. DNA synthesis was found in a small number of nuclei of non-neuronal cells, both of ecto- and mesodermal origin. The percentage of labeled cells (Labeling Index, or LI) decreased in both regions exponentially with age. On the base of measured LI values, the total number of cells arising from age one to 12 months was calculated. As the reference value the number of cells in one month-old animals was taken. The calculated cell increment in the ectodermal population in the cortex amounted to 19.7-20.6% (average 20.2%) and to 196.0-425.0% (average 247.0%) in the corpus callosum (pairs of figures correspond to values calcualted from LI values measured in sagittal and frontal sections). When all labeled cells (LC) were taken into consideration (of both ecto- and mesodermal origin) the corresponding cell increment ranged from 25.0-30.5% (average 26.8%) in the cortex and from 205.0-454.8% (average 263.0%) in the corpus callosum. The number of all newly arising cells in the whole hemisphere (including both cerebral cortex and corpus calosum) calculated from mean LI values of all LC in sagittal and frontal sections amounted to 52.0%. It is suggested that the observed DNA synthesis and cell division, particularly in the corpus callosum and mesodermal cell groups of both regions studied, correspond mainly to renewal of cell populations. In the cerebral cortex accumulation of some newly arising cells in situ cannot be excluded.


Synaptic relationships of Golgi type II cells in the medial geniculate body of the cat.

A combined analysis with the Golgi and silver-degeneration methods and electron microscopy in the ventral nucleus of the medial geniculate body has confirmed that the Golgi type II neuron forms dendro-dendritic synapses with the principal neuron in terminal aggregates called synaptic nests. Both types of neurons receive synaptic contacts from the afferent axons that ascend from the posterior colliculus and from those that descend from the auditory cortex. Only the principal neuron projects to the auditory cortex. The Golgi type II cells that receive endings from afferent axons send presynaptic processes to principal cells that are also contacted by the very same afferent axons. The axons of Golgi type II cells project to synaptic nests other than those supplied by the dendrites of the parent cell and link the Golgi type II cells with each other. On the surface of the Golgi type II cell there is a segregation of the different types of synaptic endings and a consistent sequence in their synaptic relationships. The endings of colliculogeniculate and Golgi type II axons predominate on the distal dendrites in the synaptic nests. Corticogeniculate endings congregate more on the soma and proximal dendrites. In the synaptic nests the Golgi type II dendrites are presynaptic to the principal cell dendrites, whereas both kinds of dendrites are postsynaptic to the very same axons, which project either from the posterior colliculus or from Golgi II cells...


Caliber spectra of fibers in the fasciculus gracilis of the cat cervical spinal cord: a quantitative electron microscopic study.

In order to obtain a better understanding of the microscopic structure of the cat fasciculus gracilis, entire cross-sections of the fasciculus were examined with the electron microscope. Twenty-five thousand, two hundred and eighty-four fibers were encountered in one fasciculus. The fiber caliber spectra obtained from the study show that the fasciculus gracilis at cervical level has a unique fiber distribution pattern. The fiber diameters range from less than 1 mu to 15 mu, however, 97 percent of fibers have diameters less than 8 mu; and the majority of the fibers are in the 2-5 mu range.


Area specific reflexes from normal and supernumerary hindlimbs of Xenopus laevis.

Two area specific reflexes elicited by natural stimulation of different regions of the hindlimbs of Xenopus laevis have been identified. Light or intense mechanical stimulation of the foot evokes reflex activity in the ipsilateral knee flexor nerve; moderate pressure applied to the calf evokes reflex activity predominantly in the ipsilateral knee extensor nerve. The reflex responses have been recorded electrophysiologically to overcome the limitations of behavioral observations for determining the presence of activity in particular muscles. Normal area specific reflexes are elicited in the normal ipsilateral hindlimb by stimulation of grafted supernumerary hindlimbs innervated either by hindlimb (lumbar) or by non-limb (thoracic) spinal cord segments. The area specific reflexes can be elicited only if the limb is grafted to a host younger than stage 54-55 of Nieuwkoop and Faber ('56), the stage at which reflex movements are first observed behaviorally. Abnormal reflex responses are evoked by stimulation of supernumerary limbs innervated by either thoracic or lumbar segments when the limb buds are grafted to older larvae. Supernumerary forelimbs grafted at early stages and innervated by either thoracic or lumbar spinal cord segments generally fail to elicit area specific reflex responses in the normal hindlimb. Single-unit recordings of afferent fibers supplying the normal and supernumerary hindlimbs show that each limb receives a separate nerve supply. No evidence for branched afferent fibers has been found. The implications of these results for theories of neuronal specification are discussed, particularly the hypothesis that peripheral tissues are able to specify the central actions of afferent fibers that innervate them.


A block model of the cat cochlear nucleus.

A three-dimensional block model of the cochlear nucleus of the cat was constructed from histologic sections. Boundaries of various subdivisions, based on cytoarchitectonic criteria, were included in the model. Usage of the block model in correlating physiological and anatomical data is illustrated by localizing characteristic waveforms of gross evoked responses and characteristic frequencies of single units.


Ethical considerations in human experimentation.

An accepted practice in medical research has been the subordination of individual rights to the benefit of mankind. The Nazi experiments, and other recent abuses, have focused increased attention on the dignity and rights of human research subjects and have led to new regulations to control human experimentation. Central to establishing what constitutes permissible human experimentation are the issues of risk-benefit ratio and informed consent. Evaluating the risk-benefit ratio requires consideration of the nature of the experiment, the likelihood of its success, and the type of subjects to be utilized. Participation in a study requires voluntary "educated" informed consent. Certain categories of subjects, such as children and the mentally handicapped, require special protection in this regard. Finally, formal education in medical ethics and prohibiting publication of unethical studies are likely to prove more effective in curbing unethical experimentation than increasing government regulation.


Single unit activity in the posteroventral cochlear nucleus of the cat.

Single unit activity in the posteroventral cochlear nucleus (PVCN) was recorded for a variety of stimulus conditions. The units were classified according to their response characteristics. The locations of units were plotted onto a three-dimensional block model of the cochlear nucleus. Certain types of units that responded best to the onsets of stimuli were located predominantly in the octopus cell region of the PVCN. The remainder of the PVCN, which contains a rather heterogeneous collection of small and multipolar cells, was found to contain several types of units with the dominant type being "chopper" units.


Propoxyphene bioavailability: an evaluation of ten products.

Ten commercial products containing 65 mg propoxyphene hydrochloride have been evaluated for their relative bioavailability in human subjects in a complete crossover study. No statistically significant (P greater than 0.05) differences were observed between the products in terms of plasma levels 1, 2, 3, 4, 6, 8, and 12 hours after administration; peak plasma levels; time to achieve peak plasma level; and area under the plasma level-time curve. Individual subjects exhibited considerable differences in the propoxyphene plasma levels, which were similar to the variability observed by others. The average estimated half-life of 3.61 hours was consistent with previously reported values, although it may have underestimated the true value because the low plasma levels remaining after 12 hours were not quantitated.


Single unit activity in the dorsal cochlear nucleus of the cat.

Single unit activity was examined in three component layers of the dorsal cochlear nucleus (DCN): the molecular layer, the fusiform cell layer, and the polymorphic layer (deep DCN). Electrophysiological units were classified into types on the basis of their activity under a variety of stimulus conditions. In the molecular layer spike activity was small and difficult to isolate. Almost all units in the fusiform cell layer could be classified as either "pauser" or "buildup" units. Classification of units in the deep DCN was sometimes difficult, but "pauser," "chopper," and some "on" units were found. The "on" types of units tended to be located in the more superficial part of the deep DCN. Unit locations were referred to a three-dimensional block model of the cochlear nucleus.


Some aspects of the organization of the thalamic reticular complex.

Anatomical methods which depend upon the anterograde axonal transport of isotopically labeled neuronal proteins or the retrograde axonal transport of the enzyme, horseradish peroxidase, have been used to elucidate the relationships between the reticular complex and the dorsal thalamus and cerebral cortex. Injections of tritiated amino acids in the dorsal thalamus or cerebral cortex in rats, cats and monkeys, show that as the bundles of thalamo-cortical and cortico-thalamic fibers joining a particular dorsal thalamic nucleus to its associated area of the cerebral cortex traverse the reticular complex, they each give rise to a dense zone of terminals occupying a sector of the reticular complex which is relatively constant for that dorsal thalamic nucleus and cortical area. However, because of the wide extent of the dendritic fields of the reticular cells and the degree of overlap between the sectors of the complex subtended by adjacent dorsal thalamic nuclei and adjacent cortical areas, it is likely that the reticular complex samples thalamo-cortical and cortico-thalamic activity in a somewhat unspecific manner. Fibers passing to the reticular complex from the intralaminar nuclei of the thalamus appear to be associated with the projection from the intralaminar nuclei to the striatum. Injections of tritiated amino acids in the reticular complex itself and injections of horseradish peroxidase in various other parts of the brain show that the only efferent pathway from the reticular complex terminates in the nuclei of the dorsal thalamus. The reticular complex does not appear to send fibers to other components of the ventral thalamus nor to the cerebral cortex.


The visual connections of the adult flatfish, Achirus lineatus.

Metamorphosis in the flatfish is characterized by the migration of one eye around the dorsal surface of the head to a position adjacent to the other eye on the new top side of the animal. The visual connections of the adult flatfish, Achirus lineatus, were examined. Either the migrating or non-migrating eye was removed and the animal allowed to survive for one to three weeks. Alternate sections of the brain were stained by a modification of the Fink-Heimer technique, or with cresyl violet. The diencephalic visual connections of the flatfish were similar to those of other teleosts with contralateral projections to the nuclei corticalis, dorsomedialis thalami, pretectalis, and the corpus geniculatum laterale. The distribution of the retinal efferents to the optic tectum is unique in the flatfish. In the medial one-third of the tectum, terminal degeneration was found in three bands in the stratum opticum (SO) and the stratum griseum et fibrosum superficiale (sgfs). In the middle part of the tectum, two bands of degeneration remained over the sgfs. The lateral part of the tectum has only a very small amount of degeneration distributed radomly in scattered clusters over the deep SO and superficial sgfs. The Nissl preparations also reflected the differences between the medial and lateral parts of the tectum. Distinct layer was lacking in the medial tectum with a conspicuously absent large cell layer in the stratum griseum centrale (sgc). In contrast, the lateral tectum had a typical tectal stratification. Most notable were the large neurons of the sgc.


Observations on the lateral olfactory tract of the rat.

The number and size of the axons in the later olfactory tract of the rat have been measured at several rostro-caudal levels, from material prepared for electron microscopy. Immediately caudal to the olfactory peduncle, an average of 42,000 +/- 3,000 axons were counted in the tract, while near the caudal limit of the tract an average of 32,000 +/- 2,800 axons were counted. The average internal cross-sectional area of axons measured at two levels of the tract was 1.6 +/- 1.3 mum2 and 1.1 +/- 0,9 mum2, corresponding to average internal diameters 1.4 +/- 1.3 mum and 1.2 +/- 1.1 mum, respectively. The axons in the lateral part of the tract were found to be significantly larger than those in the medial part of the tract; for one level the average cross-sectional area of axons in the lateral part of the tract was 1.6 +/- 1.0 mum2 (equivalent diameter 1.4 +/- 1,1 mum) while only 0.7 +/- 0.6 mum2 (equivalent diameter 0.9 +/- 0.9 mum) in the medial part of the tract. The thickness of the myelin sheath of the axons is generally related to axon diameter, increasing from 0.1-0.2 mum for axons 0.4 to 0.8 mum in diameter to 0.3-0.4 mum for axons greater than 2.0 mum in diameter. The ratio of the inside diameter to the outside diameter  of the fiber (ratio "g") is between 0.7 and 0.8 for most axons in the lateral olfactory tract. The axons which leave the tract laterally and medially are substantially smaller than the axons within the tract (average cross-sectional area 0.55 +/- 0.35 mum2 on the lateral side) and probably are collaterals of the axons within the tract. Unmyelinated nerve processes, probably axons, were also found in the tract. Qualitative observations from light and electron microscopical material agree well with the quantitative data, and further suggest that mixing of axons from different parts of the olfactory bulb occurs in the rostral part of the tract. This is supported by experiments with injections of 3H-amino acids into localized portions of the olfactory bulb. These indicate that there is some degree of point-to-point organization in the most rostral part of the tract, but that this is lost in the caudal part of the olfactory peduncle.


An ultrastructural study of the red nucleus in the rat.

The red nuclei of 14 adult male rats of the Wistar strain were prepared for electron microscopic study following perfusion with a mixture of aldehydes, Neurons of four size categories were identified in 1 mu Epon sections and their ultrastructural characteristics were studied in adjacent thin sections. Giant (greater than 40 mu) and large (26-40 mu) neurons are distinguished primarily by size and possess similar ultrastructural features: extensive areas of rough endoplasmic reticulum (RER), a prominent perinuclear Golgi complex, numerous mitochondria and pigment granules and a large, ovoid nucleus which occasionally contains intranuclear rodlets. Medium size neurons (20-25 mu) have less extensive, poorly organized RER and randomly distributed Golgi complexes. The nuclear envelopes of these cells frequently show multiple invaginations and continuity with the RER cisternae. In small neurons (less than 20 mu) the RER occurs as single or anastomosing strands whi le golgi complexes and pigment granules are few. In both medium size and small neurons, aggregates of condensed chromatin are adherent to the inner nuclear membrane. Three main types of synaptic terminals may be distinguished in the red nucleus: (1) small terminals with flattened vesicles and symmetrical densities (F terminals), (2) small terminals with rounded vesicles and asymmetrical densities (RS terminals), and (3) large (10-15 mu) asymmetrical, rounded vesicle terminals which form multiple contacts along their length (RL terminals). The small neurons receive both F and RS terminals on their dendrites and infrequently on their cell somas. The large and giant neurons receive F, RS and RL terminals on their somas and proximal dendrites and F and RS terminals on their distal dendrites. The somas and dendrites of medium size neurons receive both F and RS terminals but RL terminals do not lie in relation to them. Spine contacts are common throughout the nucleus and occur on both somas and dendrites.


Axonal numbers and sizes in the connectives and peripheral nerves of the leech.

The present study is an electron microscopic analysis of the numbers and sizes of axons in the connectives and nerves of the medicinal leech. In either the right or left connectives for ganglia 14-18, there are approximately 2860 (+/- 294 S.D.) axons. Ninety-seven percent of these axons are less than one micron in diameter. The median connective, Faivre's nerve, contains 97 (+/- 3 S.D.) axons, and 94% of these fibers are smaller than one micron. In the peripheral nerve roots for ganglia 14-18, there are approximately 2351 (+/- 311 S.D.) axons. Ninety-eight percent of the axons in the nerves are less than one micron in diameter. Thus, there are approximately 20,000 axons associated with each of the segmental ganglia 14-18 in the leech, and the vast majority of these fibers are less than one micron in diameter.


The projection of the retina upon the optic tectum of the pigeon.

The projection of the retina onto the optic tectum of the pigeon has been investigated using silver impregnation methods for degenerating axons and terminals, autoradiographic tracing, and the Golgi methods. Degenerating optic afferents distribute to sublaminae a-d and f of the stratum griseum et fibrosum superficiale over the whole tectum, but two major fields are observed. One occupies the caudal and ventral tectum (in which region laminar cytoarchitecture is marked), and the other rostral and dorsal tectum (where demarcation of cell laminae is relatively poor). Degeneration in the latter field is coarse and clearly distributes in a distinctly laminated fashion within the stratum griseum et fibrosum superficiale. In contrast, degeneration in the caudo-ventral region is fine, and laminated distribution less clear. The evolution of the degeneration pattern over survival periods from 3 to 56 days suggests that these laminar distributions reflect the existence of several different types of optic terminal ramification present in all parts of the tecum. A selective laminar distribution of such optic afferent types correlates well with our own and other Golgi studies. The results of the autoradiography experiments are broadly compatible with these findings.


An electron microscope study of the retino-receptive layers of the pigeon optic tectum.

The fine structure of the superficial layer of the optic tectum of the pigeon, Columba livia, has been examined both in normal animals and after unilateral eye removal. Optic afferent terminals distributed throughout sublaminae IIa-f, are principally concentrated at three depths in the retinoreceptive zone. At first, degeneration of optic afferent terminals occurs as swelling of synaptic vesicles and accumulation of neurofilaments and later as dense degeneration. There appear to be several classes of optic afferent terminals in the retino-receptive zone, as would be expected from most previous studies of the avian tectum. The non-optic components of the neuropil, which include glomerular and pleomorphic vesicle terminals, and the synaptic interrelationships between optic and non-optic components are described. Optic afferent terminals mainly make synaptic contact with the branches of radial dendrites but also, in sublaminae IIb and IIc, with the dendrites of non-radial cells. In sublamina IIc afferent terminals synapse onto the horizontal presynaptic dendrites of spindle cells and triplet synaptic arrays including optic afferent terminals, horizontal dendrites and radial dendrite profiles and radial dendrite profiles are found. This optic projection to non-radial elements in IIb c, is discussed in relation to light microscope and electrophysiological studies.


Developmental changes in olfactory bulb projections revealed by degeneration argyrophilia.

The maturation of the main and accessory olfactory bulb projections to the ventral forebrain of the golden hamster has been traced by using the Fink-Heimer silver technique to stain degenerating axons and terminal arborizations after bulbectomy at different ages between birth and 33 days. In the youngest pups, long-lasting degeneration argyrophilia (LLDA) is found in two regions of prepiriform cortex: at the level of the rostral tubercle and rostral amygdala. By five days of age the caudal region exhibiting a long-lasting degeneration reaction extends from the middle of the olfactory tubercle to the middle of the amygdala. The olfactory tubercle, medial and cortical amygdala and entorhinal cortex subsequently develop substantial LLDA at ages varying between 9 and 13 days. In a previous study (Leonard, '74b) the onset of LLDA in optic tract terminals in the superior colliculus was found to coincide with the age of eye opening and the onset of a stage of rapid snyapse formation. Since different olfactory responses appear at different times during the golden hamster pup's first two weeks of postnatal life, it seems possible that the onset of LLDA in different regions of the olfactory projection at different ages may be related to the onset of different specific olfactory functions.


The dorsal column nuclear projections to the nucleus ventralis posterior lateralis thalami and the inferior olive in the cat: an autoradiographic study.

This autoradiographic study demonstrates a topical projection of the dorsal column nuclei to the contralateral nucleus ventralis posterior lateralis thalami and the accessory part of the inferior olive. In contrast to earlier anatomical studies the projections of the gracile nucleus and the internal cuneate nucleus proved to be independent and entirely contralateral. Fibers from the gracile nucleus terminate only in the lateral part of the nucleus ventralis posterior lateralis (VPL1) and from the internal cuneate nucleus only in the medial part of this nucleus (VPLm). Projections of the gracile nucleus to the contralateral inferior olive are restricted to the caudal one-third of the medial accessory olive and the ventrolateral part of the dorsal accessory olive. The internal cuneate nucleus is only connected with the dorsomedial part of the rostral two-thrids of the dorsal accessory olive. Our material does not allow conclusions about projections from the dorsal column nuclei to other thalamic nuclei and about rostrocaudal point to point relationships between the dorsal column nuclei and the thalamus or the inferior olive.


Recovery of structure and function following transection of the primary olfactory nerves in pigeons.

Preliminary experimentation on ring doves to ascertain whether they might regulate any aspects of their reproductive behavior in terms of olfactory cues was vitiated by the discovery that their sectioned olfactory nerves had apparently regenerated. Concurrent work on frogs has shown that the olfactory receptors degenerate after axotomy and are replaced by new ones. This phenomenon was studied in pigeons. All transected nerves were found to be healed. Electrical recording from the regenerated nerves revealed apparently normal receptor function and, indirectly, autonomic reflex responsiveness. Previously untrained pigeons learned an olfactory discrimination after reconstitution of the peripheral olfactory system using a conditioned suppression procedure. The olfactory nerves of trained pigeons were sectioned and the behavioral response recovered within 16-82 days. The gross sizes of primary olfactory nerves and olfactory bulbs were frequently much less than those of controls, but on the ultrastructural level there was no recognizable morphological deficiency in the receptor cellular organelles or terminal synaptic contacts in bulbar glomeruli. Recent results by other workers indicate that pigeons utilize olfactory cues in homing performance.


Water drinking induced in sheep by angiotensin--a physiological or pharmacological effect?

The effect of val5-angiotensin II amide on water drinking in sheep was studied against a background of comprehensive data on arterial blood and cerebrospinal fluid angiotensin II levels in sheep under a variety of physiological conditions. Physiological range of blood angiotensin II concentration is 1-100 ng/100 ml. Intravenous infusion of angiotensin II within the physiological range did not increase water drinking. Intracarotid infusion of angiotensin II, or injection into third ventricle or hypothalamus, consistently caused immediate drinking of large amounts of water. Dosages necessary for effect were in the supraphysiological range. Quantitative examination of data in sheep and other species suggests that a physiological role for angiotensin II in thirst is not proved.


Hypothalamic self-stimulation in rats following immunosympathectomy or central nerve growth factor antiserum injection.

In Experiment 1, immunosympathectomized rats self-stimulated at a much lower rate on high variable ratio schedules of reinforcement than injected controls. No differences were found for responding on continuous reinforcement or low variable ratio reinforcement schedules. In Experiment 2, a similar reduction in varialbe ratio response rate was found for subjects centrally injected with nerve growth factor-antiserum relative to controls. The results suggest a reduction in central catecholamine levels as a result of antiserum treatment.


Learned helplessness in the rat.

Four experiments attempted to produce behavior in the rat parallel to the behavior characteristic of learned helplessness in the dog. When rats received escapable, inescapable, or no shock and were later tested in jump-up escape, both inescapable and no-shock controls failed to escape. When bar pressing, rather than jumping up, was used as the tested escape response, fixed ratio (FR) 3 was interfered with by inescapable shock, but not lesser ratios. With FR-3, the no-shock control escaped well. Interference with escape was shown to be a function of the inescapability of shock and not shock per se: Rats that were "put through" and learned a prior jump-up escape did not become passive, but their yoked, inescapable partners did. Rats, as well as dogs, fail to escape shock as a function of prior inescapability, exhibiting learned helplessness.


Learned helplessness in the rat: time course, immunization, and reversibility.

Rats, like dogs, fail to escape following exposure to inescapable shock. This failure to escape does not dissipate in time; rats fail to escape 5 min, 1 hr., 4 hr., 24 hr., and 1 wk. after receiving inescapable shock. Rats that first learned to jump up to escape were not retarded later at bar pressing to escape following inescapable shock. Failure to escape can be broken up by forcibly exposing the rat to an escape contingency. Therefore, the effects of inescapable shock in the rat parallel learned helplessness effects in the dog.


Stimulus generalization of suppression in rats following aversively motivated instrumental or Pavlovian training.

Following 100 or 300 avoidance training trials, instrumental subjects and their yoked Pavlovian counterparts were tested for generalization of lick suppression along the frequency dimension of the avoidance conditioned stimulus. Gradients of stimulus control were evident after 300 instrumental avoidance training trials, and additional intradimensional Pavlovian discrimination training further sharpened the gradients. After 100 trials, the yoked Pavlovian subjects suppressed more than their instrumental counterparts. However, with increased Pavlovian training, flatter gradients with decreased suppression were obtained. Results from a second experiment revealed that, whereas Pavlovian experience decreased suppression to the tone, subjects suppressed drinking in the presence of static, environmental cues. Data from both experiments supported interpretations that stress the role of response control over environmental events.


Backward conditioning in the rabbit (Oryctolagus cuniculus).

Backward conditioning of the nictitating membrane response of rabbits was studied. The prior exposure to unconditional stimulus-conditional stimulus (US-CS) pairings retarded subsequent forward conditioning. Control procedures eliminated latent inhibition and forward safety-signal effects as accounting for the data. The relevance of this report to other recent studies of backward conditioning is discussed.


Consequences of response-contingent change in unconditioned stimulus intensity upon the rabbit (Oryctolagus cuniculus) nictitating membrane response.

In a between-groups design, an instrumental contingency was superimposed on classical conditioning of the rabbit nictitating membrane response. Subjects were exposed to a tonal conditioned stimulus (CS) and, if no conditioned response (CR) occurred, a 5.0-ma. paraorbital electric shock unconditioned stimulus (US). USs of 5.0, 3.3, 1.7, and 0.0 ma., respectively, were contingent on occurrence of a CR in the CS-US interval for subjects in the 4 groups of the experiment. The group exposed to contingent US omission differed from the other 3 groups in percentage CR, onset latency, amplitude, and 2 indices of CR form, and those 3 groups generally did not differ significantly among themselves on these dependent variables. Results were interpreted to be contrary to "law of effect" formulations of classical conditioning.


Partial reinforcement effects in classical aversive conditioning in rabbits and human beings.

The partial reinforcement extinction effect (the PREE) in classical aversive conditioning was investigated in 2 experiments. In the first, the nictitating membrane responses of 120 rabbits were conditioned at a 250-msec. interstimulus interval (ISI) under continuous reinforcement, partial reinforcement with the unconditioned stimulus (US) omitted (Group PO), or partial reinforcement with the US delayed to 1,500 msec. (Group PD). These 3 groups were factorially extinguished under US-Omitted, US-Unpaired, or US-Delayed extinction regimens. A significant PREE was obtained, but only for PO training and US-Omitted extinction. The second experiment, employing human subjects in a masked eye blink conditioning task, produced parallel results. A general discrimination view of the classical PREE seems applicable, but one in which neither cognitive factors nor intertrial conditioning of reinforcement aftereffects play a significant role.


Determinants of human operant heart rate conditioning: a systematic investigation of several methodological issues.

Three methodological issues of concern within the literature on human operant heart rate conditioning were assessed utilizing a number of techniques for data reduction. The type of statistical approach largely determined the conclusions to be drawn about 2 issues: (a) differences and similarities between heart rate acceleration and deceleration learning and (b) changes in conditioning over a number of sessions. Three techniques yielded data that confounded between- and within-session shifts in tonic heart rate. A fourth method of data reduction (contrasts between pretrial and trial responding) involved no such difficulty. This method of analysis most accurately represented changes in operant heart rate that occurred within and between conditioning sessions.


Food-reinforced inhibition of conditioned salivation in dogs.

Twelve dogs salivated to a tone that was followed by food, but not to a noise for which there was an added response dependency. The noise was followed by food if and only if they did not salivate. The addition of this response dependency vitiated the classically conditioned response to the noise. A yoked-control group of 6 dogs receiving the same sequences of stimuli and food salivated to both the tone and noise stimuli.


Within-subjects positive and negative contrast effects in rats.

Rats were given alternating 1-min. access periods to 2 tubes containing either 32% or 4% sucrose solutions for daily 6-min. test sessions. Lick rate for 32% was higher under comparison (32 vs. 4) than noncomparison (32 vs. 32) conditions; and lick rate for 4% was lower under comparison conditions (4 vs. 32) than under noncomparison conditions (4 vs. 4). All sucrose conditions were varied within subjects and both positive and negative contrast were obtained with a small n. In addition to lick rate, intake and latency measures also revealed contrast effects. Deprivation conditions altered latency but not lick rate measures of contrast. Reducing the test session to 3 min. (alternating 30-sec. access periods) did not greatly affect contrast. Additional experiments provided evidence for distinct within-days and between-days contrast effects, as well as a between-groups contrast effect.


Responses of virgin mice, and of maternal females, to normal and caesarian-section delivered pups.

Pups were presented to adult mice of the Porton strain. Significantly more mothers and virgin females retrieved pups to the nest than did virgin males. More virgin females than males licked pups, built nests and assumed lactation posture. Differences were significant even if males that attacked pups were excluded from consideration. Latencies to first appearance of maternal activities were higher than reported by most other workers. Possible genetic strain differences in the response of virgin mice to pups are discussed. In Experiment 2 pups delivered by caesarian section with placentas attached were used. More mothers than either virgin males or females cleaned and accepted pups, indicating that pup cleaning may be controlled by factors different from those influencing other maternal activities.


Suppression of precocial copulation by progesterone implants in the male chick forebrain.

Precocial copulation in 2-wk.-old male chicks, described behaviorally as free mount, tread, posterior contact, waggle, peek, and seize, was developed through hand-training experience and androgen treatment. Crystalline progesterone was then implanted in various forebrain or midbrain regions. Results indicated that progesterone inhibited copulatory behavior when placed in the periventricular areas of the preoptic-hypothalamic continuum. Progesterone implants in the preoptic lateral forebrain bundle regions also suppressed precocial copulation. Forebrain implants of cholesterol did not result in copulatory inhibition. The suppression of copulatory behavior was not accompanied by loss of weight or deficits in general activity or comb growth. These data indicate that brain regions responsible for progesterone-induced copulatory inhibition are similar in neuroanatomical distribution to those involved in testosterone-induced copulatory activation.


Age and sex differences in behaviors mediated by the ventromedial hypothalamus.

Age and sex differences in behaviors mediated by the ventromedial hypothalamus (VMH) were examined in the rat. Circadian rhythm, emotionality, and taste responsiveness (except for responsiveness to quinine adulteration) were found to shift, in one or both sexes, toward a pattern suggesting decreased VMH functioning with increasing age. A post hoc analysis of the configuration of positive and negative results suggests that, for those behaviors known to show both immediate and sustained effects of VMH lesion, male rats show a marked trend toward the lesioned pattern of behavior with increasing age, whereas females show weaker or nonexistent age trends in the same behaviors. For those behaviors that have been shown to change only during the static, obese phase, or for which data re controversial as to whether changes take place as a result of the VMH lesion at all, this age and sex pattern does not emerge.


Effects of gastric loads and food deprivation on subsequent food intake in suckling rats.

Suckling rats were subjected to deprivation periods of 6-8 hr. Intake following deprivation was greater in deprived than in nondeprived sucklings, but did not increase with increasing deprivation. Gastric loads of NaCl solutions depressed subsequent intake; 3% NaCl was more effective than .9% NaCl. Other gastric loads of varying osmotic and caloric value also depressed subsequent intake. In order of increasing effectiveness in depressing intake, the gastric loads were protein hydrolystate, heavy cream, water, milk, lactose, glucose, and corn oil. Effectiveness was unrelated to osmotic or caloric value of the load. Gastric fill and, possibly, some property of carbohydrate appear to be important determinants of satiety in the suckling rat.


Voluntary selection of and tolerance to 1,2 propanediol (propylene glycol) by high and low ethanol-selecting mouse strains.

Fifteen male mice from each of 4 inbred strains (C57BL/6J, BALB/cJ, CBA/J, and DBA/2J) were tested to determine their voluntary self-selection of a 10% solution of 1,2 propanediol (1,2 PD), A 3-carbon alcohol of low toxicity. As with ethanol, the C57BL/6J strain consumed significantly greater amounts that the 3 other low ethanol-selecting strains. A second experiment determined that the 3 low selecting strains suffered significantly greater depression of the central nervous system from 1,2 PD than the high selecting C57BL strain. It was also found that ethanol is  a much more potent depressant that 1,2 PD. These results are discussed in terms of the possible role of neural sensitivity in regulating consumption levels of the 2 alcohols.


Some observations on the preference deficits produced by lateral preoptic lesions in the rat.

Following water drprivation, rats with lateral preoptic (LPO) damage lose the normal preference for glucose solutions. Food deprivation reinstates the preference. This dependency is specific to sweet-tasting fluids, and the deficit persists even if thirst is alleviated prior to the preference test. Such rats will drink sweet solutions in response to intravascular fluid depletion, but they are deficient in response to sweet solutions under nondeprived conditions. This last finding in particular suggests that hunger and palatability, as determinants of the response to sweet solutions, may be dissociated by LPO damage.


Effects of gastric loading on the sucking response and voluntary milk intake in neonatal piglets.

The effects of loading the stomach of piglets with 100 ml of milk after 6 hr of fasting and immediately before allowing them access to the dam were studied. Piglets gained less weight and rested more often on preloaded days. This suggests that gastric receptors exist and signal distension of the stomach. Monitoring sucking responses to a rubber teat revealed that although preloading the stomach substantially reduced voluntary milk intake during the initial 10-min. period of the test, the vigorous oral activity continued largely unabated. Isotonic saline suppressed the voluntary milk intake of the piglets for a shorter period than milk or isotonic glucose solution.


Functional organization of the rat amygdala with respect to avoidance behavior.

Bilateral electrolytic lesions in the periamygdaloid piriform cortex of female albino rats produced marked disruptive effects on the acquisition of active avoidance responses in a 1-way as well as a 2-way test situation, significantly impaired passive avoidance behavior, and inhibited feeding in a novel environment. Lesions in each of the 6 major subdivisions of the amygdala (cortical, medial, central, intercalated, lateral, and basolateral nuclei) consistently produced facilitatory effects on active avoidance behavior in 1-way as 2-way situations. Passive avoidance behavior was impaired in animals with lesions in the central, intercalated, and basolateral nuclei. Damage to the anterior amygdaloid area or the the nuclei of the lateral olfactory tract did not reliably affect active or passive avoidance behavior.


Suppressive and enhancing effects of footshock on food-reinforced operant responding following septal lesions in rats.

Effect of septal lesions on suppression of an intermittently food-reinforced lever press by contingent and noncontingent footshock was measured. Rats with septal damage maintained higher response rates than did intact animals under both contingent and noncontingent shock. Furthermore, the difference in suppression produced by the contingent and noncontingent conditions was approximately the same for the experimental and control groups. In a second experiment, performance was measured during counter-conditioning in which the correlation between contingent shock and positive reinforcement was varied. Rats with septal lesions responded at higher rates than did controls. When only reinforced responses were punished, this lesion-induced elevation represented an increase above baseline performance without punishment. This finding suggests that the effect of septal damage on appetitive instrumental performance cannot be due solely to a deficit in response inhibition.


Free operant avoidance in rats under increased nitrogen pressures.

Rats performed on a free operant avoidance schedule with a response-shock interval of 20 sec. and a shock-shock interval of 2 sec. Avoidance response rates increased and shock frequency decreased when the rats were exposed to elevated pressures of both air and a nitrogen-oxygen mixture in a hyperbaric chamber. Increases in response rates were related to raised partial pressures of nitrogen at 89.0 psi and 111.3 psi. Conditional probabilities of interresponse times indicated that increases in response rates were not due to disruption of temporal discrimination. Increased avoidance rates under pressure suggested direct excitatory effects of high pressures of nitrogen.


Neuromuscular blocking drugs and heart rate changes after direct nerve stimulation and during classical conditioning in cats.

Two experiments investigated cardiovascular responses to several common neuromuscular blocking compounds. Experiment 1, employing 16 cats, assessed ganglionic transmission in sympathetic and parasympathetic systems controlling heart rate and blood pressure after d-tubocurarine chloride (d-T.C.), dimethyl d-tubocurarine iodide (D. d-T.I.), succinylcholine chloride (SC), or saline. Cardiovascular responses to sympathetic stimulation were essentially unaffected at drug levels that blocked evoked electromyograms; however, vagally evoked bradycardia and corresponding blood pressure decrease were blocked by d-T.C. and redduced by D. d-T.I. and SC. Experiment 2 compared heart responses of 12 cats under the same blocking compounds during differential classical aversive conditioning. Differential conditioned responses and unconditioned responses occurred under D. d-T.I., less under SC, but not under d-T.C. However, animals trained under d-T.C. and tested under D. D-T.I. showed differential conditioned responses.


Biometrics of reversal learning in mice: III. complete reciprocated Mendelian analysis.

A total of 118 subjects, divided into high scoring 129/J and low scoring DBA/1J parents, F2, and reciprocated F1, B1, and B2 generations, were given reversal training for 50 sessions. Results showed that the parent strain providing genes that were more favorable to reversal learning provided a maternal environment that was significantly less favorable than that provided by the other parent strain. There was also found to be significant nonalletic interaction, a genetic factor the presence of which had not been suggested by the results of earlier work using the diallel cross method.


Vulnerability of skeletal and autonomic manifestations of memory in the rat to electroconvulsive shock.

A series of experiments was performed to probe the phenomenon of sparing of memory by electroconvulsive shock (ECS) when amnesia is assessed by autonomic indices. Differential vulnerability of memory as indexed by skeletal and autonomic responses was determined to be a function of a higher threshold to disruption for autonomically indexed memories. Autonomic responses spared by ECS were found to reflect underlying memory rather than artifact produced by nonassociative factors arising from the interaction of conditioned stimulus (CS), unconditioned stimulus (US), and ECS. Furthermore, retrograde amnesia gradients of different slopes were observed with skeletal and autonomic measures. Two interpretations of these phenomena are discussed. One hypothesis suggests that individual components of a memory are consolidated at different rates, whereas the other concerns the differentail sensitivity of various measures in assessing memory.


Effects of stimulus similarity in discrimination training upon wavelength generalization in pigeons.

Thirty pigeons were given variable interval training to peck a 555-nm. light and then were tested for wavelength generalization. The subjects were later assigned to 1 of 3 groups, matched for both relative generalization slope and response rate. One group then received successive discrimination training between the 555-nm. stimulus (S+) and a vertical white line on a 555-nm. background (S minus); another group experienced the same S+ but a vertical white line on a black background as S minus. A third group received a comparable amount of single stimulus training with the 555-nm. value. On a second wavelength generalization test, the first group yielded greater sharpening of generalization than the second group, whereas the third group showed no change from Test 1. These results indicate that the sharpening of generalization gradients by discrimination training is directly related to the similarity  of the discrimination training stimuli.


Food-deprivation-induced behavioral arousal: mediation by hypothalamus and amygdala.

Electrolytic lesions of the basomedial hypothalamus eliminated food-deprivation-induced stabilimeter activity in rats that were prevented from becoming obese. Knife cuts lateral to the basomedial area (separating the medial and lateral hypothalamus) potentiated this activity, as did transections posterior to the basomedial region. Anterior transections (between anterior and medial hypothalamus), however, eliminated the effect. Lesions of the stria terminalis and amygdala likewise abolished deprivation-induced locomotor activity, but elevated ab-lib activity to a level comparable with that after deprivation in intact animals. Animals with combined basomedial-stria terminalis lesions behaved like animals with basomedial lesions. These results suggest that food-deprivation-induced locomotor activity in stabilimeter cages is due to a disinhibition of the basomedial hypothalamus by the amygdala via the stria terminalis.


Acoustic startle reflexes in the rat during consummatory behavior.

Auditory startle reflexes were elicited in thirsty rats when they were drinking water or were between drinking boutsmthe reaction was greater during drinking, this enhancement developing over the first few seconds after drinking onset. The startle reaction was lowest immediately after the termination of drinking. Reflex enhancement was reduced when thirsty rats drank milk rather than the more preferred water. The reflex was smaller with increased water deprivation, but enhancement produced by drinking was apparent at all levels of deprivation studied, satiety to 4-days deprivation. The inhibitory effect of a preliminary stimulus was not affected by consummatory behavior. Attention is drawn to suggestive parallels between these behavioral effects and other consequences of consummatory activity, primarily having to do with electrophysiological events and arousal processes


Some behavioral effects of transecting ventral or dorsal fiber connections of the septum in the rat.

The behavioral effects of large electrolytic lesions in the septal area were compared with those of knife cuts that severed the ventral or dorsal connections of this structure. Rats with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All three operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle box avoidance response, The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a one-way avoidance response.


Intrahemispheric response competition between vocal and unimanual performances in normam adult human males.

Subjects balanced a dowel rod vertically on the left and right index finger singly and while simultaneously repeating phrases. With right-handed subjects who had no left-handed relatives, concurrent verbalization shortened right- but not left-handed balancing. Increased phonetic difficulty of the phrases produced an increased decrement on right-handed balancing, but left-handed balancing was unchanged; it also produced more verbalization errors on trials with the right hand, but not with the left. Concurrent verbalization shortened balancing duration with both hands of left-handers. Right-handers with left-handed relatives produced variable results. Concurrent humming also selectively interfered with right-handed balancing. It was concluded that the results conform to an interpretation based on intrahemispheric interference between incompatible, simultaneously produced sets of responses.


Electroretinographically determined spectral sensitivity in the tawny owl (Strix aluco).

The electroretinographic (ERG) responses to single light flashes and to flickering lights were obtained in the tawny owl (Strix aluco). The waveform of the single-flash responses indicated that the owl possesses a duplex retina. Spectral sensitivity was determined with light flickering at a 6 and 25 Hz. The sensitivity curve obtained from the 6-Hz responses has a broad maximum between 500 and 525 nm. The 25-Hz sensitivity curve is narrow with a peak at about 600 nm. The sensitivity curves are compared with behaviorally measured sensitivity curves of the pigeon. A close agreement is found between 25-Hz curve and the pigeon red modulator.


Auditory similarities associated with genetic and experimental acoustic deprivation.

Susceptibility to audiogenic seizures has been produced in otherwise non-susceptible mice by acoustic stress and by conductive hearing loss. Both procedures temporarily elevate the absolute threshold of the auditory evoked potential (AEP) and are maximally effective during a circumscribed period of early development. In the genetically SUSCEPTIBLE DBA/2J mouse, AEP thresholds indicated that its auditory system is functionally less mature during this early period than that of the nonsusceptible C57BL/6Jmouse. It was proposed that innate susceptibility found in the DBA/2J mouse results from auditory disuse supersensitivity during a critical developmental period, in support of Saunders' hypothesis for acoustically primed mice. The increased peak-to-peak AEP amplitudes, however, were not believed to be causally related to the audiogenic seizures.


Auditory masking-level differences in the cat.

Four cats were trained to avoid shock by responding to the intermittent occurrence of 1-kHz tone pulses at one ear, while a continual train of noise pulses was simultaneously presented either to the signal ear alone or to both ears. Using the masked threshold levels determined with monaural noise as a reference, the amount of unmasking produced by the addition of noise to the nonsignal ear was measured. Significantly lower tonal detection thresholds were observed when noise equal in intensity to that at the signal ear was added to the nonsignal ear. Additional unmasking occurred when the intensity of the noise at the latter ear was raised to a level 10 db. higher than that at the signal ear.


Habenular lesions and feminine sexual behavior of ovariectomized rats: diminished responsiveness to the synergistic effects of estrogen and progesterone.

Bilateral electrolytic lesions in the habenula resulted in disruption of estrogen-progesterone-evoked feminine sexual behaviors of ovariectomized female rats. There were no difference between lesioned and sham-operated animals in tests conducted after the administration of estrogen alone. Animals with lesions were characterized by an increased proportion of mounts not followed by lordosis, a decreased proportion of mounts followed by pronounced lordosis, and a decreased proportion of mounts preceded by soliciting behaviors. Lesions had a negligible effect upon the tendency to hold lordotic postures after the male dismounted. The results suggested that the habenula is involved in modulating responsiveness to the synergistic effects of estrogen and progesterone.


Ontogeny of spontaneous locomotor activity in rabbit, rat, and guinea pig.

Postnatal locomotor activity was investigated in rabbit, rat, and guinea pig. A peak was found in this behavior at 5 days of age in the rabbit and, in confirmation of earlier studies, at 15-20 days in the rat. Neonatal guinea pigs showed no variation in activity levels due to age. The guinea pig is born at an advanced stage of neural maturation in comparison with the rat, and the rabbit is born at an intermediate stage. This difference accounts for the observed variations in postnatal activity profiles if it is assumed that the behavioral peak coincides with the transition from a stage of primarily mesencephalic arousal system maturation to a stage of primarily diencephalic and telencephalic inhibitory system maturation.