Developmental and behavioural functions in young children with elevated blood lead levels. Blood lead levels in some pre-schoolchildren living near a lead works and particularly in some children with fathers employed at the lead works showed evidence of increased exposure. Forty-seven of them took part three years later in a follow-up study of their developmental and behavioural functions. The children were aged between 4 and 5 1/2 years and were closely matched for age, sex, social class, parental education, area, and length of residence. Only three children had moved house since their blood lead levels had been examined at two years of age; these levels ranged between 18 and 64 microgram/100 ml. None of the children had clinical symptoms of plumbism. No statistically significant (P less than or equal to 0.05) differences were found on developmental and behavioural scores when the children were divided into two groups of less than or equal to 35 microgram/100 ml (n = 23) and greater than 35 microgram/100 ml (n = 24). The differences in scores were of the same order as those between boys and girls, which were themselves generally not significant. Behaviour ratings did not differ. The variations in developmental skills were generally found to be more related to age and schooling; neither these factors nor the difference in sex was related to blood lead levels.


The hazard of old lead mines in Wales.

The hazard of old lead mines in Wales. Two population surveys were conducted near old lead workings in Wales. The first, at Y Fan in the middle of Wales, gave evidence suggestive of a gradient in blood lead level, highest in subjects resident close to the contaminated spoil heaps, and lowest in those who lived in farms some distance away. However, the gradient was significant (P less than 0.05) only in males, and all but one of the blood lead levels were below 2.0 mumol/l. In the second survey, at Halkyn in North Wales, levels in subjects living in the area contaminated by spoil were compared with those in subjects living in a nearby industrial area, and with subjects in a market town some distance away. Mean blood lead in people living in the three areas were homogeneous. These studies give no evidence that old lead workings in Wales are a serious hazard to health.


Cleft lip and palate in the Oxford area. An examination of the evidence for clustering in space and time. Children with cleft lip and/or palate born during the period 1965-74 inclusive in the Oxford area were examined for evidence of any tendency for clustering. The methods suggested by Knox (1963), David and Barton (1966), and Smith and Pike (1974) were used. No clustering was evident in space or in time. There was some indication of clustering in space-time for isolated cleft palate during the period 1965-71, but this was not repeated during 1972-74.


Renin and aldosterone relationships in manic depressive psychosis. The paper describes a two-month period of study in four bipolar manic-depressive patients in a metabolic ward. Plasma renin activity, packed cell volume, plasma sodium and potassium were determined at intervals. Twenty-four-hour urinary sodium, potassium and creatinine were also estimated daily. Aldosterone production rate was measured on two occasions for each patient. Three of the patients showed at least one episode each of mania and depression during the study, while the fourth patient, who was receiving prophylactic lithium throughout, had one ten-day depressive episode but was otherwise normal. No obvious relationship between mood and plasma renin activity was observed, but the group showed a high resting renin activity, a blunted renin response to posture, and inappropriate aldosterone production rates for the renin activity found. It is postulated that a primary defect in the aldosterone-renin system may be present in bipolar manic-depressive psychosis.


Hormone responses to methylamphetamine in depression: a new approach to the noradrenaline depletion hypothesis. The corticosteroid response to methylamphetamine was lower in ten patients when they were depressed than when they were recovered (P less than .026). The growth hormone responses to the same injection in the depressed and recovered states were not significantly different. This pattern of responses is seen in normal subjects after blockade of alpha adrenergic receptors. These findings may indicate a functional deficiency of noradrenaline at alpha adrenergic receptors in these patients during the time they are depressed.


A study of predictive factors in depressive disorders of poor outcome. A retrospective comparison was made between two groups, each consisting of 30 depressed patients, one in which the outcome following discharge had been good, the other where it had been poor. A previous psychiatric history, earlier admission for psychiatric illness, particularly for affective disorders and a poorer performance on routine intelligence tests were found in the poor prognosis group. In this group the duration of the index admission was longer and the condition of the patient was less improved at the time of discharge. Several symptom variables also discriminated between the groups. These findings are discussed.


Diagnosis 'uncertain': a follow-up study. During a ten year study, 10% of patients at a general hospital in-patient unit had unsolved diagnostic problems at the time of discharge from hospital. These 132 cases were designated 'uncertain' and were followed up. Eighty-three patients were ultimately diagnosed, and 300 consecutive in-patients discharged from the same unit with a definite diagnosis were also studied. The clinical features and diagnoses of the two groups were compared. Special features associated with uncertainty were: a presenting complaint of pain; apathy without apparent mental or physical cause; hallucinosis or major paranoid symptoms without other good evidence of psychosis. Age was found to be relevant; compared with patients receiving confident diagnoses, those with uncertain diagnosis due to depressive psychosis were more often younger, while those due to neurosis or personality disorder tended to be older. Atypical psychotic depression was the condition most commonly associated with diagnostic doubt.


Social skills training of out-patient groups. A controlled study of rehearsal and homework. Fifty-one out-patients with social skills deficits (two-thirds men) completed ten weekly sessions of 75-minute group treatment; 44 were followed up for a mean of 16 months. Random assignment was to one of three conditions: (I) Cohesive group discussion; (2) Modelling and role-rehearsal; or (3) Modelling and role-rehearsal + daily social homework. All three treatment conditions produced significant but incomplete improvement at the end of treatment and follow-up. The two role-rehearsal conditions were significantly superior to group discussion on several measures. Patients who completed daily social homework assignments did significantly better than patients who completed control homework. Alcohol and drug abuse patients usually dropped out. Schizophrenic patients in remission had lost their improvement at follow-up. Patients with other diagnoses retained their gains to 16-month follow-up.


A typology of parasuicide.

A typology of parasuicide. Parasuicide is not a single syndrome. Subtypes at present recognized are based largely on clinically derived stereotypes. When considering a series of patients, the clinician is unable to handle more than a few attributes at a time. This paper describes the application of three very different clustering algorithms to a material of 350 treated parasuicide patients. Mathematically, three types emerge. Clinically, two of these are interpretable and make sense. The types established are: I (n = 107) a group not characterized by any of the variables we examined; this group is a puzzle, mainly because the reasons for the parasuicidal act are not clear. II (n = 132) a depressed, alienated group with high life-endangerment. III (n = III) a group whose act was highly operant: they felt alienated and were angry with others. These groups did not differ significantly on demographic variables. The usefulness of this typology, particularly for management, after-care and prevention, has now to be assessed.


Dynamic scintigraphy in clinical urology. The technique of isotope renal scintigraphy using Technetium-99m labelled agents and a gamma camera system on-line to a digital computer is described. Its value in diagnosing renal space-occupying disease and renovascular abnormalities is emphasised. A method of measuring individual renal haemodynamics and the possible potential of such techniques are discussed. Radio-isotope studies are rapid, simple, non-invasive and non-toxic. They give information complementary to that from urography.


Computed tomography of the kidney.

Computed tomography of the kidney. The application of computed tomography to the diagnosis of kidney disease and the features of renal neoplasms, cysts, hydronephrosis, inflammatory parenchymal lesions and other pathological processes are described. The diagnostic accuracy of computed tomography is excellent when compared with ultrasound and selective renal arteriography. This new non-invasive technique can obviate the need for arteriography in a significant number of morphological diseases of the kidney and is especially useful in defining the extent of malignant tumours.


The prevalence of calcified upper urinary tract stone disease in a random population--Cumbernauld Health Survey. It is difficult to obtain the true prevalence of stone disease in community. A proper random sample of a population has been studied and a figure of 3.83% of calcified stones have been found in 2,000 subjects. The significance of biochemical, bacteriological, skeletal and other surgical abnormalities is discussed. It is now possible to study individual groups within the population with respect to stone disease.


Long-term follow-up 100 cases of renal calculi. Phosphatic calculi form in infected urine. Complete clearance is associated with sterile urine. This disease is distinct from metabolic stone disease and should be curable if all stones are removed and postoperative infection is prevented.


Partial nephrectomy for stone disease.

Partial nephrectomy for stone disease. The results of 227 partial nephrectomies for stone were reviewed. Radiologically visible calcification remaining in the kidney at the end of the operation increased the risk of further stone formation. Ipsilateral and contralateral true recurrence rates after partial nephrectomy were the same, and increased with time up to 34% at 20 years. Ipsilateral recurrence rates after partial nephrectomy were half those found in a similar study of nephrolithotomy, pyelolithotomy and ureterolithotomy. Anatomical factors are important in stone formation, and partial nephrectomy is of value in the management of renal stones.


Can angiography stage renal carcinoma?

Can angiography stage renal carcinoma? We have compared the staging of renal carcinomas in 36 patients as judged preoperatively by angiography (T stage) and postoperatively by histopathology (P stage). Using the standard abdominal aortogram and selective renal arteriogram we found a considerable error rate in T staging (40%). The commonest error was preoperative overstaging, and this is probably determined by the behaviour of renal carcinoma, rather than by inadequate angiography. We conclude that whilst renal arteriography remains a useful diagnostic aid, it cannot answer questions on tumour extent with any accuracy. Staging by histopathology is essential for proper assessment and management of these patients.


The obstructed kidney: correlation between renal function and urodynamic assessment. In 20 patients with pelvi-ureteric junction obstruction the results of quantification of the change in renal pelvis size during high-dose intravenous urography with a diuretic, pressure/flow studies, standard renography and deconvolution analysis of the gamma camera renogram have been compared. The results of high-dose intravenous urography and pressure/flow studies correlated well. Renography was unreliable in diagnosing obstruction unless deconvolution analysis of the gamma camera renogram was used to differentiate those showing an obstructive uropathy from those with an obstructing nephropathy.


Radionuclide cystography in the management of vesico-ureteric reflux. Direct radionuclide cystography in 100 patients has been shown to be a useful investigation in the diagnosis and management of reflux and a valuable complement to radiographic methods; it may well have a place in the detection of reflux in the infected patient. The advantages include low radiation exposure, an accurate measurement of residual urine volumes, simplicity of technique and the use of materials and equipment that have in recent years become increasingly available for routing investigation.


Ureteric advancement in the treatment of reflux. Among 91 children requiring surgical correction of major ureteric reflux, 58 had 1 or 2 ureters treated by an advancement operation. This proved to be highly effective in preventing further reflux and in no case did any ureteric obstruction develop. The indications for choosing this operation, and a suitable operative technique, are described.


The unstable bladder--fact or artefact?

The unstable bladder--fact or artefact? 100 patients, referred for urodynamic study, have had several cystometrograms performed at each examination, and the effect of filling at different rates and in different positions has been assessed. This has included pressure measurements carried out during "physiological" bladder filling. Bladder instability was found to be a highly consistent phenomenon, its detection being independent of filling rate or position of filling.


Interstitial cystitis, treated by prolonged bladder distension. 25 patients with interstitial cystitis were treated by prolonged bladder distension. 16 patients are symptom-free, but 5 of these have had 1 or more previous prolonged bladder distensions. 6 patients are improved, whilst 3 remain symptomatically unchanged. Prolonged bladder distension can be repeated successfully when symptoms return. These results suggest that prolonged bladder distension has a place in the treatment of interstitial cystitis.


Abacterial cystitis.

Abacterial cystitis. 5 young male patients with all the symptoms and signs of genito-urinary tuberculosis but in whom no organism could be cultured from the urine are described. 4 of them rapidly responded to a course of tetracycline. Various organisms are suggested as a cause of this condition, and careful bacteriological investigation in the future might discover the cause.


Psychiatric aspects of recurrent cystitis in women. Using both psychometric questionnaires and psychiatric interview it has been shown that women with recurrent cystitis have significantly more psychiatric symptoms (particularly those of anxiety) than the population as a whole. By comparison with the expected prevalence, the study group shows a 3-fold increase in psychiatric symptoms antedating micturition symptoms, and a 10-fold increase in psychiatric symptoms overall. Significant differences in psychometric profiles have been demonstrated between different clinical subgroups of patients (e.g. bladder instability, outlet obstruction and dyspareunia). A multifactorial approach (including an awareness of psychiatric factors) to patients complaining of recurrent cystitis can produce a treatment failure rate as low as 4.4%.


The effect of N-acetyl cysteine on cyclophosphamide cystitis. Further studies on the effect of various compounds of the rat bladder after treatment with cyclophosphamide are reported. The results show that N-acetyl cysteine is a highly effective drug for the prevention of cyclophosphamide cystitis. N-acetyl cysteine does not significantly impair the anti-tumour effect of cyclophosphamide.


T1 bladder tumours.

T1 bladder tumours. 167 patients with T1 bladder transitional cell tumours treated by transurethral resection or cystodiathermy are reviewed. The overall crude survival was 83.2% in 3 years and 71.8% in 5 years. 7.8% of the patients developed an invasive tumour and these patients had an unfavourable initial tumour with moderate or poor differentiation and high or moderate mitotic rate. High or moderate pleomorphism was particularly unfavourable. Multiple tumours did as well as single ones but more of them had invasion of the lamina propria and a larger number were treated by either radiotherapy or cystectomy.


A toxicity study of the treatment of T3 bladder tumours with a combination of radiotherapy and chemotherapy. 18 patients with category T3 bladder cancer were treated with a combination of radical radiotherapy followed after an interval of 1-3 months by pulsed chemotherapy with adriamycin and 5-fluorouracil. Providing the chemotherapy was limited to 4 cycles, there was no serious toxicity and the regime was well tolerated.


The treatment of advanced bladder cancer with methotrexate. 61 patients with advanced bladder cancer were treated with methotrexate. 3 different regimes were used, 2 given on an out-patient and 1 on an in-patient basis. A response rate of 56% was found in patients who received 100 mg of methotrexate intravenously every 2 weeks as an out-patient. Provided that renal function is checked before therapy and is normal, then methotrexate can be used safely; it being well tolerated and having few serious side-effects.


Scottish prostates: a 6-year review.

Scottish prostates: a 6-year review. A review of all prostatectomies performed by urologists in Scotland during 1969-1974 is presented. Factors influencing the mortality rate are discussed and the steady increase in low-mortality (1.4%) transurethral prostatectomy noted.


Potency and prostatectomy.

Potency and prostatectomy. A prospective questionnaire study with a 6-month follow-up was carried out to determine the incidence of post-prostatectomy impotence. 57% of patients were potent at the time of operation. A man with full potency had a 4% chance of becoming totally impotent and a 3% chance of becoming partially impotent. A man with failing preoperative potency had a 10% chance of becoming totally impotent and a 22% chance of becoming worse. No particular method of operation was at fault. One-third of potent men claimed to have some postoperative ejaculation.


Continuous irrigation of the bladder after prostatectomy: its effect on post-prostatectomy infection. The incidence of post-prostatectomy bacteriuria was measured in patients having no continuous bladder irrigation postoperatively, in those irrigated for 24 hours with chlorhexidine 1/5,000, and in those irrigated with normal saline. The infection rate after saline irrigation was greater than after chlorhexidine, but the infection rates after chlorhexidine irrigation and drainage alone were similar. The infection rate was higher in older patients, in those treated with retropubic rather than transurethral prostatectomies, in those who had postoperative catheters for more than 4 days, and in those admitted in acute retention of urine. The increase in infection rate associated with acute retention was seen only in the group treated with drainage alone postoperatively. Chlorhexidine irrigation appears to reduce the infection rate in these cases.


Early diagnosis of prostatic carcinoma: the role of transurethral resection. The exclusion of prostatic carcinoma in TUR specimens represents a considerable problem for the histopathologist. A technique for the separation of tissue on an anatomical basis which has been carried out on 50 patients is presented. It permits more representative histological sampling of TUR specimens and more accurate characterisation of prostatic carcinoma, but further refinement is recommended.


Urine hydroxyproline excretion--a marker of bone metastases in prostatic carcinoma. 24-hour urinary hydroxyproline excretion (THP), a marker of bone collagen metabolism, has been measured in 35 patients with carcinoma of the prostate. 21 patients had bone metastases diagnosed by bone scanning (99mTc MDP). All 9 patients with metastases studied before hormonal treatment and the majority of those on treatment had elevated levels. Patients with negative bone scans invariably had normal THP levels. Furthermore, THP reflected the presence of bone metastases more accurately than plasma alkaline or acid phosphatase. Serial THP levels altered predictably with symptomatic response to treatment. These results suggest that THP is more reliable than other markers of the presence and activity of bone metastases in response to treatment and may have been neglected in favour of more elaborate and costly X-ray and isotope investigations.


Choice of operation to promote micturition after spinal cord injury. 61 male patients who had resection of the bladder neck alone, internal membranous urethrotomy alone or a combination of the 2 procedures to establish micturition after cord injury are reviewed. The combined operation has the greatest chance of initial success and should be performed if no attempt is to be made or preserve sexual function. Internal membranous urethrotomy is appropriate for lesions at all levels of the cord. Cystometry and cystourethrography are not helpful in the choice of operation.


The detection and localisation of abdominal lymph node metastases from testicular teratomas. Review of the results of treatment of 275 patients with testicular teratomas indicates that the size of para-aortic node metastases as defined by lymphography is closely related to prognosis, and that accurate definition of these metastases is essential in planning treatment. Although para-aortic lymphadenectomy does not appear to be necessary therapeutically or as a staging procedure, excision of residual bulk disease may be required after chemotherapy and radiotherapy. In these cases the residual para-aortic tumour mass should be accurately localised by ultrasonography so the best surgical approach can be used.


Prolactin gonadotrophins in 208 men presenting with infertility. Prolactin, FSH and LH were measured in the plasma of 208 male partners of infertile marriages. We found 1 case of marked hyperprolactinaemia in 82 oligozoospermic men (1.2%). There was no difference in the mean prolactin levels of men with normal sperm counts and men with oligozoospermia or azoospermia. One-third of the men with azoospermia and with sperm density of less than 10 million had marked FSH elevation and our experience confirms the work of others that this indicates a poor prognosis.


Reinnervation, myelination and organization of iris tissue implanted into the rat midbrain--an ultrastructural study. The ultrastructure of autologous irides implanted into the midbrain of mature Sprague-Dawley rats was studied over a time period of 4-14 days. Most features of the normal iris still persisted throughout this time, including typical iris blood vessels and amelanotic melanocytes. At 5-4 days after implantation, the normal innervation of the implanted iris had degenerated, except for the presence of intact Schwann cells and some myelin debris. Reinnervation, beginning about the seventh day, proceeded rapidly. By the fourteenth day, extensive reinnervation of the implant was evidenced by the presence of numerous small (0.1-0.6 micrometer) and large (2-4 micrometer) non-myelinated axons ensheathed in Schwann cell cytoplasm. Axonal varicosities, filled either with dense core or clear core vesicles, formed junctions with axons. These junctions were characterized by an accentuation of areas of the axonal membrane and pre- or post-junctional thickenings; however, we did not observe typical synaptic complexes. Some large axons within the myelinated iris developed thick myelin sheaths of the peripheral nervous system (PNS) type; we believe this is the first reported instance in which myelination of central axons by Schwann cells within the brain parenchyma has been produced by the implantation of PNS elements.


Effect of undernutrition on cell generation in the adult rat brain. Cell proliferation and cell death in the lateral ventricular subependymal layer were studied in acutely food-deprived and chronically undernourished 6-week-old rats. The length of the cell cycle was increased by 40-75%, while the DNA synthesis phase of the cycle was prolonged by 70-85%. The rate of cell acquisition was reduced to approximately half the control level, and the proportion of degenerating cells was significantly increased. The response to undernutrition of proliferating cells in the subependymal layer of adult rats differs from that in animals in the first two weeks of life, and resembles that seen in other tissues.


Release of (3H)norepinephrine from a clonal line of pheochromocytoma cells (PC12) by nicotinic cholinergic stimulation. Release experiments were carried out in vitro with a clonal line of rat pheochromocytoma cells (designated PC12) which synthesize and store catecholamines and which, after treatment with nerve growth factor (NGF), cease cell division and extend neuronal-like processes. In the present study, PC12 cells were exposed to [3H]norepinephrine (NE) which they took up and stored in reserpine-sensitive sites. Exposure of such cells to nicotinic cholinergic agonists resulted in release of [3H]NE into the external medium. Release terminated within 1 min and partially returned after 20 min in the absence of agonist. After 1 min of stimulation with nicotine, NGF-treated cells released 5-6% of their contents of [3H]NE while NGF-untreated cells released 1-2%. Release from both NGF-treated and -untreated PC12 cells was inhibited in the absence of Ca2+ or by elevated Mg2+ and was blocked by the nicotinic antagonists D-tubocurarine and mecamylamine (50% inhibition at 0.1 and 0.06 micrometer, respectively). Release was not affected by the presence of tetrodotoxin. Such findings suggest that release of [3H]NE from PC12 cells may be mediated via stimulation of nicotinic acetylcholine receptors and a consequent stimulation-secretion coupling mechanism.


Influence of dietary calcium and phosphorus on metabolism and production in laying hens. 1. The effects of different dietary concentrations of calcium (24 to 56-9 g/kg) and phosphorus (4-5 to 14-2 g/kg) on production and some aspects of metabolism were studied in laying hens. 2. Treatments did not affect egg numbers, food consumption, conversion efficiency of food to egg, bodyweight gain or mortality. 3. Increasing dietary calcium (Ca) significantly increased plasma Ca and inorganic phosphorus (P), breaking strength at the radius and egg specific gravity and significantly decreased plasma alkaline phosphatase and egg weight. 4. Increasing dietary phosphorus increased plasma P and decreased egg specific gravity significantly. 5. Plasma Ca, P and alkaline phosphatase and radius breaking strength were suitable indices of the Ca status of the hens.


The secretion of glucose into the egg of Gallus domesticus and observations on the uterine secretion of cations. 1. The concentrations of glucose, K+, Na+ and Ca2+ were measured in the uterine fluid and albumen of eggs removed from the shell gland at intervals of from 6 to 20 h after the previous oviposition. 2. A steady increase in the concentrations of glucose and K+ occurred in the uterine fluid during the initial 13 h of the egg's sojourn in the gland, resulting in their diffusion into the albumen. Meanwhile Na+ concentrations of the fluid and albumen decreased. 3. After 14 h in the gland and until oviposition there was little change in the concentrations. 4. Uterine fluid drained artificially from the gland using a Perspex egg had lower glucose and K+, but higher Na+ concentrations than the normal fluid. 5. The rates of secretion of glucose and K+ measured with the artificial egg resembled their entry rates into the normal egg, but there was an apparent deficit in Ca2+ secretion.


Effect of extended photoperiod on the spermatogenic activity of chicken-pheasant hybrids. 1. Males of chicken-pheasant hybrids and non-breeding pheasants were exposed to photoperiods of 10 or 20 h/d to test the effect of light on spermatogenic activity. 2. Testicular weights of hybrids and pheasants exposed to 10 h/d were similar and extending the photoperiod did not increase this in hybrids, although it caused a 48-fold increase, and complete recovery of spermatogenic activity, in pheasant. 3. Extending the photoperiod caused an increase in the number of primary spermatocytes and a corresponding decrease in the number of spermatogonia in hybrids, however, stages beyond primary spermatocytes were not present. This suggests that the stimulus of extending the photoperiod, while sufficient to induce meiosis in existing germ cells, is not enough to effect proliferative bursts or to overcome the meiotic arrest in the hybrids.


Effect of transportation on blood metabolites in broilers. 1. Groups of 30 broilers from seven flocks were bled and weighed at the farm and a further sample of 10 broilers from each flock was transported from 8 to 16 km to the laboratory prior to bleeding and weighing. 2. One haematological and 11 biochemical analyses were made on each blood sample. 3. Although transportation did lead to significant differences in certain variables, the trends were consistent and sampling following transit is considered acceptable for clinical pathology studies.


Transfer of 125I to eggs in hens fed on diets containing high-and low-glucosinolate rapeseed meals. 1. An experiment was designed to evaluate the effect of the glucosinolate content of rapeseed meal on the transfer of dietary iodine to eggs. 2. The experimental diets, containing two concentration (50 or 100 g/kg) of high-or low-glucosinolate rapeseed meal and a diet, devoid of rapeseed meal, all supplemented with 0-3 mg I/kg were given to laying hens for 6 weeks before oral administration of 125I daily for 11 d. 3. The percentage of 125I transferred to egg yolk was significantly reduced by the inclusion of high-glucosinolate rapeseed meal but not by low-glucosinolate meal. 4. Determination of the total iodine content of egg yolk indicated that there was some reduction in the transfer of dietary iodine to eggs even with the low glucosinolate rapeseed meal.


Effects of temperature treatments on the heat production of starving chickens. 1. Heat production was measured for about 24 h at six temperatures from 2 to 35 degrees C on individually starved broilers that had been subjected to four treatments; these were acclimated or unacclimated to these temperatures, or to these temperatures for 12 h and to 22 degrees C for 12 h (alternated) during each 24-h period. 2. Response curves relating heart production and environmental temperature for the four different treatments differed significantly. Only the unacclimated birds subjected to the alternated temperatures increased heat production at 35 degrees/22 degrees C. Major effects of acclimation were observed mainly in the cold. 3. The relationship between daily endogenous nitrogen (N) excretion and heart production (mg N/kJ) was constant at the different temperatures, but acclimation and alternating temperature increased N excretion. 4. Evaporative heat loss was reduced by alternating temperature at the high temperatures, and by maintaining temperature constant in the cold.


Clinical signs of fatty liver and kidney syndrome in broilers and their alleviation by the short-term use of biotin or animal tallow. 1. Birds affected by fatty liver and kidney syndrome (FLKS) had elevated concentrations of serum Na+, K+, lactate, pyruvate and uric acid and reduced concentrations of serum HCO-3 and glucose. 2. Short-term treatment with biotin or animal tallow reduced the mortality from FLKS and prevented the clinical signs. 3. Lactic acidosis may be a major factor contributing to the mortality and physical symptoms observed in birds affected by FLKS. The lactic acidosis and the hypoglycaemia observed in FLKS are due primarily to an accumulation of pyruvate as a result of an insufficiency of biotin for normal pyruvate carboxylase activity.


Gonadotrophin concentrations during growth and maturation in domestic turkeys. 1. Circulating immuno-reactive-luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured between hatching and either 17 or 30 weeks of age in turkeys. 2. In one experiment both sexes were reared together. The pattern of changes in gonadotrophin concentration with age consisted of high LH concentrations at 3 to 8 and 16 to 19 weeks old and FSH peaks between weeks 3 and 10 and at weeks 18 and 19. 3. In two separate experiments male and female birds were reared separately for 17 weeks. In these turkeys the LH concentration was high for 3 weeks following hatching and also after 10 weeks, while FSH  was elevated at weeks 10 and 15 in females and at weeks 7 and 13 in males. 4. There were lower plasma LH concentrations in turkeys which had received testosterone implants while the FSH concentration was elevated. 5. Pinealectomy in female turkeys led to increased FSH concentrations at 2 weeks but depressed FSH concentrations thereafter.


The effect of cytochalasin B on the endosteal lining cells of mammalian bone. A scanning electron microscopic study. The lining osteoblasts of the rat tibial endosteum were treated for various times (between 1 and 60 min) and increasing doses (3.87-38.7 microgram/ml) with the macrolide fungal metabolite cytochalasin B (CB). Dimethylsulfoxide (DMSO) served as the vehicle for CB and was administered to control tissues. An in vitro incubation system and scanning electron microscopy (SEM) were used to evaluate the effects of CB. The drug initiated cell rounding (contraction), nuclear protrusion, bleb formation, and the subsequent clustering of blebs and microvilli into aggregates. All CB-induced aberrations of the surface structure were readily reversible when tissues were washed with CB-free media. DMSO had no significant effect on cell surface morphology. The reversible structural changes brought about by CB are explained in terms of alterations of the subplasmalemmal cortical microfilament system of osteoblasts. The potential use of CB in evaluating the bone cell cytoskeleton and its relationship to the physiology of the cellular functional membrane (endosteum) of bone is discussed.


Stages in the dissolution of human enamel crystals in dental caries. Various stages in monocrystal dissolution occurring during human enamel were studied by high resolution transmission electron microscopy. After the development of a central core lesion, two mechanisms by which the dissolution spread laterally to the (100) faces of the crystal could be demonstrated on the basis of the systematic orientation of the crystallographic axes. In the first case, the destruction was developing parallel to (120) planes and the borders were limited by (100) planes. In the second type, the development of the lateral side lesion was observed parallel to (100) planes. The carious destruction of the enamel monocrystal occurred as a result of the development of several lateral side dissolutions of the two types described, proceeding along the entire central core lesion.


Mechanism of induction of hypercalcemia and hyperphosphatemia by lead acetate in the rat. The present study is an investigation of the mechanism of hypercalcemia and hyperphosphatemia induced by the intravenous injection of lead acetate (Pb-Ac). A total of 118 male rats were injected with 30 mg/kg of Pb-Ac, or with 16.5 mg/kg of sodium acetate as the control. The levels of serum calcium, phosphorus and lead were then determined at various time periods after the injections. Serum calcium and phosphorus levels increased with time after Pb-Ac injection and the maximum values of calcium (17 mg%) were found after 1 h and of phosphorus (13.5 mg%) after 30 min. Both calcium and phosphorus levels reverted to the normal range after 12 h. The maximum net rates of increase of calcium and phosphorus were found immediately after Pb-Ac injection. At that time, deposition of lead at the calcifying sites of bone and incisor dentin was demonstrated by a histochemical examination. In other experiments the changes in the calcium and phosphorus contents in the medium after shaking bone powder in serum with Pb-Ac in an in vitro system were studied. It was confirmed that the calcium and phosphorus were displaced from the bone mineral, the extent of the displacement being correlated with the concentration of the Pb-Ac added to the medium, and that these displacements were very rapid reactions. These results suggest that hypercalcemia and hyperphosphatemia following Pb-Ac injection results from a direct action of lead on the bone mineral.


Diffusion of 45Ca in bovine enamel.

Diffusion of 45Ca in bovine enamel. The penetration of 45Ca ions into whole bovine enamel from an aqueous solution was studied as a function of the Ca content in the solution. A sectioning technique was employed to measure the penetration of 45Ca into the enamel. Probably only Ca ions occupying surface positions in the hydroxyapatite crystallites participate in the exchange process at the solution-enamel interface. The fraction of Ca ions participating in the exchange was 2% of the total number of Ca ions. Two different diffusion processes occur; firstly, a process governed by a diffusion coefficient, D1 ranging from about 5 x 10(-14) to 2 x 10(-12) cm2/s and strongly dependent on the calcium concentration in the solutions; and secondly a process with a concentration-independent diffusion coefficient, D2, with a value of 2.8 x 10(-12) cm2/s. It is assumed that the 2 diffusion types correspond to intra- and interprismatic transport, respectively. A model based on the pore structure of dental enamel and on surface charges on hydroxyapatite crystallites is discussed.


Relations between tensile impact properties and microstructure of compact bone. Standardized human and beef femoral compact bone specimens were tested in tensile impact and the dynamic mechanical properties were determined. The microstructure of 45 beef and 47 human bone specimens were examined histologically to determine if there is a structural basis to account for strength differences in the bone samples. Strong negative correlations were obtained between the maximum stress and the percentage area of secondary osteons in each specimen. For human bone samples, the energy absorption capacity and the modulus of elasticity were also found to have strong negative correlations with the percentage area of secondary osteons present in each specimen. Linear regression equations were obtained describing the impact strength properties in terms of the percentage areas of secondary osteons and cavities in the samples. Fracture surfaces of the tested bone specimens were examined in a scanning electron microscope. Most surfaces exhibited a fairly rough texture indicating a quasi-cleavage type of failure. Fractographic analysis of bone fracture surface was helpful in understanding the micromechanics of bone fracture.


Density and composition of trabecular and cortical bone in perinatally irradiated beagles with chronic renal failure. Bone density and composition were studied in trabecular and cortical bone from control 2 and 4 year old beagles and those which had various degrees of renal failure as a result of perinatal irradiation. Changes in the two types of bone were qualitatively similar but consistently greater in trabecular bone. In a group identified as markedly uremic, the decrease (P less than 0.025) from control levels in specific gravity was about 4 times greater in trabecular than in cortical samples. The decrease (P less than 0.025) in grams of ash/ml was 9% in trabecular bone and 2% in cortical bone. These changes were associated with an increase (P less than 0.001) in water content and, on a percent by volume basis, approximately equal decreases in ash (P less than 0.025) and combustible matter (P less than 0.025). In a mildly uremic group there were similar trends in mean values but the only significant difference was an increase (P less than 0.001) in trabecular bone water.


The effects of crystal size distributions on the crystallinity analysis of bone mineral. The mechanisms by which crystal size distributions affect the usual method of quantities X-ray diffraction analysis of bone mineral have been determined on synthetic crystals. It was observed that each component of a crystal-size distribution diffracts independently. This independence causes systematic nonlinear behavior in the plot of integrated intensity vs. broadening parameter curves. The nonlinearity resulted in an overestimation of the amount of nondiffracting material present in bone mineral. Because crystal size distributions may vary for different crystallographic directions, it is strongly suggested that the usual practice of adding the c-axis and a-axis integrated intensities to estimate the crystallinity of the sample be discontinued. Methods of understanding the crystal size distribution function in bone mineral are discussed and evaluated.


The measurement of Ca2+ effluxes from bone. To facilitate the study of membrane function in the control of the flow of ions into and out of bone, it was desirable to develop a system for the direct quantitation of unidirectional effluxes of calcium and phosphate from bones. Based on a mathematical analysis of the problem, a specially designed Ussing chamber was developed which proved successful. Calvaria from 2-day-old rat pups, 3-day chicks and adult mice were evaluated. Calcium influxes which exceeded the corresponding effluxes were observed in the neonatal calvaria but not with those from adult mice. Also, an asymmetry in efflux was observed in rat calvaria, the inner side of the skull showed a higher efflux than did the external side. No such asymmetry was seen with calvaria from chicks or mice. This new technology should permit a further exploration of the role of the bone membrane in electrolyte homeostasis.


Ultrastructural analysis of glycosaminoglycan hydrolysis in the rat periodontal ligament. I. Evidence for macrophage involvement in bone remodelling. We identified the cellular sites of glycosaminoglycan hydrolysis by localizing a key enzyme, N-acetyl-beta-glucosaminidase, in the rat periodonatal ligament. Reaction product was seen in osteoclasts, osteoblasts, fibroblasts, and in macrophages situated perivascularly in areas of bone remodelling. The preferential location of macrophages in areas of both bone formation and bone resorption, and their intense NAGase activity identified the macrophage as a significant participant in the total process of bone remodelling. We considered the presence of reaction product in the Golgi zone and the rough endoplasmic reticulum of osteoblasts and fibroblasts as possible localization of a NAG-transferase.


Ultrahistochemical analysis of glycosaminoglycan hydrolysis in the rat periodontal ligament. II. Aryl sulfatase and bone resorption. The distribution of aryl sulfatase in the rat periodontal ligament was investigated by ultrastructural histochemistry. In the periodontal ligament aryl sulfatase was localized specifically in osteoclasts and in vicinal perivascular macrophages. Macrophages associated with bone formation did not stain. The authors interpret this specificity as a potential marker for osteoclast differentiation from macrophages--or as a further indication of the capacity of macrophages to modulate their enzymatic complement in response to the environment. To explain the absence of aryl sulfatase in areas of bone formation we suggest that different sulfate esters are mobilized from resorbing and mineralizing matrices, and that only the enzyme associated with bone resorption is histochemically detectable with the artificial substrates currently used.


Estrogen-induced sequential changes in avian bone metabolism. Medullary bone was induced in male Japanese quail by administration of estradiol valerate. An increase in the organic weight of the femur was observed by 36 h after estrogen and an increase in ash weight was observed by 96 h. A complex sequence of metabolic changes in the femur occurred after estrogen treatment. A large increase in uptake of 3H-proline associated with enhanced collagen formation began 36 h after estrogen and reached a peak 3.5 times the control rate at 60 h. The onset of mineralization of the newly formed bone matrix, as determined by 45Ca uptake, began about 24 h after onset of collagen synthesis indicating that synthesis of the bone matrix and its mineralization occur sequentially. Large increases in the rates of uptake of 3H-uridine and 3H-thymidine occurred prior to the onset of medullary bone formation and appear to reflect the differentiation of osteogenic precursors to bone-forming cells.


Partition of inorganic ions and phospholipids in isolated cell, membrane and matrix vesicle fractions: evidence for Ca-Pi-acidic phospholipid complexes. Electrolytes and phospholipids of cartilage fractions were partitioned by extraction with organic and aqueous solvents into six solubility groups: Electrolytes I, II and III, and Lipids I, II and III. Of the total Ca, only 4% was water soluble (Electrolytes I); 4-12% was complexed with lipids (Electrolytes II); while the majority (84-92%) was insoluble (Electrolytes III). In contrast, nearly half of the Mg and Pi were water soluble. Of the neutral phospholipid, 95% was not complexed with mineral ions (Lipids I), but 30-45% of the acidic phospholipid was (Lipids II). Ca/Pi ratios were extremely low in the water-soluble phase, but were in the range of amorphous calcium phosphate (ACP) in the insoluble. Molar ratios of the lipid-mineral complex were: Ca:Mg:Pi:acidic phospholipid, 4:3:2:2. Mg/Ca ratios in the soluble fraction were high (5.5-8.9), sufficient to stabilize ACP. Kinetic studies revealed rapid turnover of soluble Ca, insoluble turning over much more slowly. Labeling of lipid-complexed Ca was rapid in cells, but occurred later in matrix vesicles, suggesting transfer. While lipid-Ca-Pi complexes can nucleate apatite in vitro, those present in vivo inside matrix vesicles apparently do not because of the excess Mg. We conclude therefore, that in vesicle-mediated calcification, lysis of the membrane may be essential to allow release of internal Mg.


The temperature dependency of 45Ca diffusion in bovine enamel. The diffusion of 45Ca ions in sound bovine enamel at pH 7.0 was studied as a function of temperature in the range 20 degrees-40 degrees C. The experimental data show that the diffusion is governed by two processes with activation energies of about 0.7 and 1.3 eV respectively. These values are considerably larger than the activation energy of calcium ion diffusion in water (0.2 eV). The diffusion process with the activation energy of 1.3 eV is dependent upon the calcium concentration in solution. A model  based on the complex pore structure of enamel and on interactions of diffusing ions with the enamel constituents is discussed.


Ultrastructural study of amelogenesis imperfecta. An ultrastructural study of teeth with amelogenesis imperfecta revealed various aspects of microcavities in the enamel surface, which ranged from isolated imprints of ameloblasts corresponding to the mildest lesions at the end of amelogenesis, to pits caused by the death of 20 to 30 ameloblasts at the beginning of amelogenesis. Abnormalities in the shape of the prisms can be observed. Further, crystals are distributed randomly within a prism or at the junction of 2 contiguous prisms while intercrystalline spaces are widened, indicating in various places the lack of a preferred orientation of the crystals. In amelogenesis imperfecta, two different crystalline periods are found: 1 of about 250 A, the other of about 500 A and over. The fact that amorphous areas are found among the crystals of enamel may be related to different stages of crystallization. However, it was not possible to find any lattice defect.


Demonstration of enamel matrix proteins on root-analogue surfaces of rabbit permanent incisor teeth. The continuously erupting rabbit incisor tooth is normally thought of as having an enamel covered "crown" on its labial surface and a cementum covered "root" on its lingual surface. We have examined both surfaces of continuously erupting rabbit incisor teeth taken from near term embryos by a variety of means, including transmission and scanning electron microscopy, biochemical fractionation, and immunohistochemistry. In all cases, we could detect no qualitative difference in the early extracellular matrices taken from the labial and lingual surfaces of the teeth. Both matrices were shown to be composed of dentin and enamel, although the thickness and geometry of the enamel matrix on the lingual surface was somewhat different from that on the labial surface.


[Study of the element secretory glands of a tubicolous polychaete (Pectinaria (= Lagis) koreni) with the help of electron microprobe and ion microanalyzer (author's transl)]. Two histophysical methods (electron microprobe and ion microanalyzer) were used on sections of Annelids in order to study the inorganic composition of cement secretory glands. Mg, Ca and P were demonstrated in large amounts in the secretions, associated with organic matter. Traces, or no, Fe, Al and Si were found. Possibilities of artifacts are discussed, and these results are compared with biochemical methods. A hypothesis is proposed in order to explain the differences observed between biochemical and present results, which suggest, for the hardening of cements a different chemical mechanism to that suggested by Vovelle in annelid Sabellaria alveolata.


Further observations on the fine structure of cellular cementum from deciduous teeth of pigs. Examination of microradiographs from the deciduous teeth of pigs revealed large lacunae or radiolucent zones close to the cemento-dentinal junction. Electron microscopic studies of the ground sections showed areas of irregularly shaped zones devoid of mineral and filled with collagen fibers. In the wide unmineralized zones, spherical clusters of crystallites were noted. Several cementum lacunae bordered by a broad rim of unmineralized collagen fibers were noted and some lacunae also contained zones of a moderately electron dense material. This material did not yield a diffraction pattern, while the mineralized part of the cementum gave the diffraction pattern typical of hydroxyapatite.


An x-ray study of the paracrystalline nature of bone apatite. X-ray diffraction from oriented bone sections show that the crystalline apatite content of untreated mature cortical bovine bone has, in fact, a paracrystalline structure (i.e., no long range order). There is anisotropy in both lattice distortions and the sizes of the coherently diffracting domains. The paracrystalline mean distance fluctuations (g) were found to be 1.5 (+/- 0.1)% and 2.9 (+/- 0.2)% for the basal and prism planes respectively, the corresponding paracrystalline sizes being 220 (+/- 20) and 70 (+/- 10) A. The paracrystalline structure became more ordered above 600 degrees C, suggesting the association of hydroxyl and possibly carbonate and other ions with the paracrystalline structure. The paracrystalline model for bone apatite helps explain anomalies between X-ray and electron microscope measurements of crystal size and also more of the biological functions of the crystalline apatite.


Luminescence quantum yields of sound and carious dental enamel. The absorption and emission spectra of slabs of human and bovine dental enamel were determined. The absorption and scattering coefficients and emission quantum yields were computed according to theoretical models. The samples were gradually demineralized. The absorption, scattering, and emission parameters were determined as a function of the demineralization time. Using the theoretical models combined with the experimental values, ratio of the visible and UV luminescence, and the decrease of visible emission intensity upon demineralization are explained.


Evidence for the presence of numerous protein components in immature bovine dental enamel. The proteins and peptides of immature enamel were extracted from freshly slaughtered bovine embryos in solutions containing protease inhibitors. No detectable differences were noted in the number of components, their overall amino acid composition, or molecular weights from the proteins and peptides extracted 12-16 h postmortem in solutions which contained no protease inhibitors. These data indicate that the large number of components found in developing bovine enamel is not due to proteolysis occurring during their isolation. Significant amounts of protein components having molecular weights greater than approximately 15,000 were not detected. Therefore, if the ameloblasts initially synthesize only a few high molecular weight protein species, the present data imply that in vivo degradation of the high molecular weight enamel proteins occurs very rapidly after their synthesis and precedes the massive loss of protein which accompanies the final stages of enamel mineralization and maturation.


The early mineralization of enamel. Fine structural observations on the cellular localization of calcium with the potassium pyroantimonate technique. The potassium pyronatimonate technique was used to study the cellular distribution of calcium during the early mineralization of enamel in rat molar tooth germs at the electron microscope level. Differing patterns of calcium distribution were observed in the ameloblast seemingly associated with the appearance of Tomes' process. In the early secretory ameloblast calcium pyroantimonate deposits were observed within the Golgi apparatus, within coated vesicles, within mitochondria and associated with the inner aspect of the cell membrane. However, with the development of Tomes' process the ameloblast no longer demonstrated these discrete deposits of calcium pyroantimonate. Instead they showed a diffuse cytoplasmic staining pattern with no preference for any particular organelle.


[Histochemical localization of calcium in the colloid of rat thyroid vesicles (author's transl)]. With a Glyoxal bis 2-hydroxyanil alcoholic solution at -25 degrees C, the calcium was localized in frozen thyroid slices. The limited ionic movement permits seeing that the calcium situated principally in the colloid is resorbed at the same time by a low temperature stress.


Histone proteolysis in fish erythrocyte nuclei. The erythrocyte histones of trout, carp, white sucker, and chicken are subject to very different levels of autolytic activity. Carp erythrocyte histones extracted from typical nuclear preparations suffer extensively from degradation; histones 1, 5, and 3 (H1, H5, and H3 respectively) are preferentially cleaved and characteristic peptides designated P1, P2, and P3 appear during the course of proteolysis. Generally, erythrocytes from different fish species yield highly disparate proportions of H1 and H5, but this is not a consequence of the variable levels of proteolytic activity in these species. Phenylmethylsulfonyl fluoride (PMSF) (1.0 mM) was found to be superior to 50 mM sodium bisulfite as a protease inhibitor and was well suited for use in media employed for cell washes and the isolation of nuclei. Nonetheless, in carp erythrocytes residual protease activity (qualitatively the same as the uninhibited activity) persists even in the presence of PMSF. It is activated during cell lysis and remains associated with the nuclear fraction of the lysate during subsequent washes. The isolation of intact nuclei is important for the ultimate extraction of undegraded histone, especially from sources in which the risks of autolysis are high or unknown.


Fructose-induced adenine nucleotide catabolism in isolated rat hepatocytes. The mechanism of fructose-induced nucleotide catabolism was studied using isolated rat hepatocytes in which the adenine nucleotide pool was prelabelled with [14C]adenine. Incubation of these cells with fructose caused a rapid depletion of the adenine nucleotides and a corresponding increase in allantoin. There was no accumulation of radioactivity in adenosine in the presence or absence of the adenosine deaminase inhibitor 9-erythro-(2-hydroxy-3-nonyl)adenine. This confirms the previous hypothesis that fructose-induced adenine nucleotide catabolism occurs by way of AMP deaminase (AMP amino-hydrolase, EC 3.5.4.6).


Increased lipoprotein lipase activity of skeletal muscle in cold-acclimated rats. The activity of lipoprotein lipase (LPL) in the heart, diaphragm, and soleus muscles was markedly increased in cold-acclimated rats and it was even greater in rats treated with oxytetracycline (OTC) while exposed to cold. Other skeletal muscles studied had low and variable activities which were not significantly increased by cold acclimation or by cold plus OTC treatment. It appears therefore that, apart from the heart and the muscles involved in respiratory movements, LPL activity is primarily associated with those muscles which contain a predominance of slow-twitch oxidative fibers, and that the enzyme in muscle, heart, and diaphragm responds to cold acclimation and cold plus OTC treatment in a parallel fashion in these tissues.


Loss of body fat during an arctic winter expedition. Fifty-five soldiers have been observed over a vigorous 10-day sledging patrol in the Canadian arctic and subarctic. Initial observations showed a low level of physical fitness (26% body fat, aerobic power 41.9 +/- 7.8 ml kg-1 min-1, handgrip force 43.7 +/- 7.2 kg). Over 2-week northern sojourn, energy expenditures as measured by a Kofranyi-Michaelis respirometer and diary observation averaged 3248 kcal (13.6 MJ) day-1, with a small (152 kcal (633 kJ)) positive daily energy balance. A weight loss of 1 kg, presumably water, was made good within 1 week of return to the south. A fat loss of some 3.9 kg was probably attributable largely to the demands of lean tissue synthesis. The lean mass was increased by 3.9 kg over the trial, with parallel gains of muscle force and aerobic power. The rapid mobilization of depot fat led to marked ketonuria.


Effect of the linoleic acid concentration of mother's diet on adenyl cyclase activity of fetal and neonatal rat brown adipose tissue. An adenyl cyclase activity was measurable in the brown adipose tissue of fetal rat, and could be stimulated in vitro by noradrenaline during the last 3 days of fetal life. The stimulating effect of noradrenaline was maximal at birth and decreased during the first days of extrauterine life. Ingestion by mother of a high lipid diet modified the developmental pattern of fetal adenyl cyclase. The linoleic acid content of mother's diet had no effect on the noradrenaline- or fluoride-stimulated specific activities except on the day 22 of gestation. Relative noradrenaline-stimulated activity, expressed as a fraction of the maximal activity, was significantly increased in fetuses and 1-day-old newborns from mothers fed a high linoleic acid diet, but no effect was observed in suckling newborns.


CNS control of the PNS-mediated gill withdrawal reflex and its habituation. Removal of the branchial (Br) nerve input to the gill significantly reduced the latency and increased the amplitude of the gill withdrawal reflex evoked by siphon stimulation. Further, after Br removal repeated siphon stimulation which previously resulted in habituation now resulted in facilitation of the flex. However, the synaptic input to gill motor neurons in the abdominal ganglion continued to decrement as before. In preparations without the peripheral nervous system (PNS), removal of Br did not produce similar results. The gill withdrawal reflex and its habituation are mediated by the PNS, but the CNS exerts facilitatory and suppressive control. Thus, changes in synaptic efficacy to gill motor neurons in the abdominal ganglion are not the ultimate cause of gill reflex habituation. Habituation is the result of adaptive neural processes which occur together in the abdominal ganglion, the PNS, and the peripheral terminations of the central motor pathways to the gill. Therefore, in any analysis of the underlying neural mechanisms of habituation all these loci must be included and taken into account.


Presynaptic modulating effects of GABA on depression, facilitation, and posttetanic potentiation of a cholinergic synapse in Aplysia californica. The effects of gamma-aminobutyric acid (GABA) have been studied on the synaptic depression, frequency facilitation, and posttetanic potentiation (PTP) of a unitary, monosynaptic, and presumably cholinergic excitatory postsynaptic potential (EPSP). This EPSP, produced by minimal stimulation of the right visceropleural connective, was recorded in cell R 15 of Aplysia californica. Perfusion with GABA (10(-4)-10(-3) M) reduces the size of all EPSPs produced by a train of 100 stimuli at 1/s. It also reduced the synaptic depression and PTP, and increases the frequency facilitation seen during the train. GABA does not significantly effect the membrane resistance (mean 102%) but it slightly depolarizes (mean 6 mV) the postsynaptic cell. GABA does not reduce an acetylcholine iontophoretic potential produced on R15. The effects of GABA are reduction when chloride is replaced by acetate but they remain significant. Picrotoxin and bicuculline fail to antagonize GABA. Addition of sodium azide or dinitrophenol does not reduce the action of GABA and even prolongs it. The effects of GABA are attributed to two sites of action: a postsynaptic one, responsible for the small change in potential and partially responsible for the reduction of EPSP size; and a presynaptic one, responsible for a further reduction of EPSP size and the changes of depression, facilitation, and PTP.


Glass electrode measurement of net Na+ and K+ fluxes in erythrocytes of the spontaneously hypertensive rat. The exchange of Na+ and K+ in rat red cells at 40% hematocrit incubated in a physiological salt solution containing 1 MM ouabain was monitored with ion-specific glass electrodes. Because this system measures a change in the activity of an ion as a logarithmic function of its preexisting level, delta[K+]o is more accurately measured than delta[Na+]o; within this limitation, the downhill ion movements were close to 1:1 over the temperature span from 37 to 3 degrees C. These transmembrane movements are reasonably well expressed in terms of first-order kinetics and an Arrhenius plot constructed for K+ as the accurate indicator of the exchange yields an activation energy of 12 kcal/mol. A well-defined reversal of the usual direct relation of temperature to exchange rate was observed between 6 and 3 degrees C. The net ion movements were distinctly faster at low temperature in cells from rats with spontaneous hypertension (SHR-Okamoto) than in cells from matched controls (Woodlyn and WKY).


The role of prostaglandins in hypertension. I. The release of prostaglandins by aorta strips of renal, DOCA-salt, and spontaneously hypertensive rats. The release of prostaglandin-like (PG-like) material by aorta strips of normotensive and hypertensive rats has been studied in vitro. When incubated in an oxygenated Krebs solution kept at 37 degrees C, aorta strips removed from 8- and 12-week-old spontaneously hypertensive (SH) rats generate 1.2-2.5 times more PG-like material than aorta strips from age-matched normotensive Wistar (NW) rats. The overproduction of PG-like material by aorta strips of SH rats did not precede the development of hypertension in SH rats. Aorta strips derived from renal and DOCA-salt hypertensive rats produced 1.5-3 times more PG-like material than aorta strips from NW rats. The production of PG-like material by aorta strips of renal and DOCA-salt hypertensive rats was largely reduced when hypertension was interrupted in these animals, thus suggesting that the alteration taking place in the arteries of hypertensive rats (namely increased production of PGs) during the development of hypertension was reversible. The production of PG-like material by aorta strips of hypertensive rats was inhibited by indomethacin. Analysis of the PG-like material by bioassays and thin-layer chromatography suggests the presence of PGE2 and PGE1. The possible involvement of these PGs in the pathogenesis of hypertension in rats is discussed.


The effect of hypertonic infusions on hepatic blood flows and liver volume in the cat. The effects of intravenous and intraportal infusions of hypertonic NaCl and glucose solutions on the resistance and capacitance vessels of the intact feline liver were studied. All doses infused produced vasodilation of the hepatic artery. A rough estimate would suggest that the tonicity changes equal to those seen after hemorrhage might produce an increase of arterial conductance to no less than 110% and no greater than 140% of control conductance. In response to intravenous infusions, portal flow increased to the same extent as did arterial flows. The resistance vessels were equally affected by equal osmolal loads of glucose or NaCl but the hepatic volume changes were quite different depending on the substances infused. In marked contrast with the resistance vessel response to hypertonic NaCl, the hepatic capacitance vessels did not dilate. Liver volume decreased but whether due to mild capacitance stimulation or water egress from hepatocytes is not known. Cessation of the infusion resulted in increases of hepatic volume to above control levels. Glucose produced consistent steady increases in volume that may have been associated with fluid uptake by the hepatocytes in conjunction with glucose uptake.


The interventricular septum: an isolated perfused model for assessing myocardial function. Classical models for assessing myocardial function suffer from either a potentially anoxic central core or an unsophisticated perfusion system. We have improved Langer's perfused interventricular septum model by adapting it for parabiotic resuscitation, thus achieving rapid stability and significantly less edema. The new model, which consists of a triangular piece of rabbit interventricular septum, perfused through its septal artery, first undergoes a stabilization period of 30 min during parabiotic perfusion from another rabbit. An arteriovenous shunt is then opened and the preparation remains stable for 2 h of perfusion in which fresh blood is recirculated nonparabiotically. It is proposed that during this period, experimental interventions could be undertaken using each septum as its own control. The behaviour of 66 preparations was consistent with classical concepts of myocardial function. Simple measurements were identified for beat-to-beat functional assessment. Contractility was measured by maximum active tension and maximum differential of tension. Relaxation was measured by maximum negative differential of tension and, in the presence of ischemic contracture, changes in resting tension. Compliance was measured by septal length at a specified resting tension. Perfusability was measured by the relationship between pressure and flow.


The calcium-magnesium interaction in the process of release of noradrenaline by nicotine. The calcium-magnesium (Ca2+-Mg2+) interaction in the process of nicotine-induced release of [3H]noradrenaline ([3H]NA) from rat isolated vas deferens was studied. Increasing extracellular concentrations of Mg2+ caused a dose-dependent depression of release of [3H]NA by nicotine, and this inhibitory effect of Mg2+ was overcome by raising the concentration of CA2+. It is concluded that Mg2+ antagonizes the nicotine-induced increase in the Ca2+ influx into the adrenergic nerve terminals, and that nicotine acts on adrenergic neuronal membrane rather than intraneuronally to cause release of NA.


Neuronal depressant effects of diethylester derivatives of excitatory amino acids. The effect of iontophoretically applied kainic acid diethylester (KDEE) on the firing rate of feline spinal interneurones was investigated and compared with the action of glutamic acid diethyles (GDEE) and aspartic acid diethylester (ADEE). All these esters reversibly reduced spontaneous neuronal firing and increased spike height, KDEE being the most active of this group. KDEE decreased response to glutamate, acetylcholine, and peripheral field stimulation, showing that its depressant action is not due to a selective antagonism of an excitatory putative transmitter.


Presynaptic depression of synaptic response of Renshaw cells by adenosine 5'-monophosphate. The action of AMP (adenosine 5'-monophosphate) on synaptic transmission of Renshaw cells has been studied in cats under Dial anaesthesia. AMP applied iontophoretically reversibly reduced synaptic responses of Renshaw cells evoked by stimulation of ventral roots, as well as their spontaneous firing; however, there were no marked effects on discharges of these cells caused by iontophoretic application of acetylcholine, asparatate, and glutamate. On the other hand, AMP had no comparable effect on synaptic responses of dorsal horn interneurones evoked by stimulation of dorsal roots or their spontaneous discharges.


The effects of cholecystokinin and cholecystokinin-octapeptide on intestinal lymph flow in the rat. Intravenous cholecystokinin and its synthetic C-terminal octapeptide were found to cause a transient augmentation of intestinal lymph flow in the rat. Concomitant increase in lymph protein transport suggests that this reflects the increase in intestinal blood flow which is known to occur in response to these agents.


The nature of adrenoceptors in the guinea pig cerebral cortex: a microiontophoretic study. 1. Noradrenaline, isoprenaline, and phenylephrine have been applied my microiontophoresis to neurones in the guinea pig cerebral cortex. All three compounds produced depression of neuronal firing, and all could be antagonized to some extent by phentolamine or propranolol. 2. The responses to isoprenaline were substantially reduced in size after a few applications. Noradrenaline and phenylephrine responses were partially reduced at the time of isoprenaline insensitivity, and the responses could now be blocked completely by phentolamine. 3. The results suggest that two kinds of receptors are present in the guinea pig cerebral cortex, with properties similar to alpha and beta receptors in the periphery. A single receptor with intermediate properties would not readily explain the present results. 4. The results are not consistent with the proposal that alpha receptors mediate neuronal excitation, and beta receptors inhibition in the cerebral cortex. 5. It is also suggested that the failure of some previous studies on guinea pig cortex in vitro to demonstrate the presence of beta receptors may be due to the particularly rapid desensitization of these receptors.


Leptospira interrogans serotype pomona in Saskatchewan: isolation from a naturally infected striped skunk. Leptospira interrogans serotype pomona was isolated from the kidneys of a normal striped skunk (Mephitis mephitis hudsonicus) collected near Kindersley, Saskatchewan. Although there were no gross lesions, small foci of chronic interstitial nephritis were observed microscopically. This is the first reported isolation of serotype pomona for the prairie provinces.


Vesicular-arbuscular mycorrhizae of Easter lily in the northwestern United States. The vesicular-arbuscular (VA) mycorrhizal fungi of commercially grown Easter lily (Lilium longiflorum Thunb.) were studied. Soil and root samples were collected monthly from March through September 1975 from five fields in the coastal area of southern Oregon and northern California. Soil seivings were inoculated onto clover, onion, and lily to cause infections resulting in the production of many new mycorrhizal spores facilitating identification. Four VA mycorrhizal species were found: Acaulospora trappei, A. elegans, Glomus monosporus, and G. fasciculatus. All four VA species infected Easter lily, clover, and onion. Acaulospora trappei and G. fasciculatus were the most commonly isolated species from all five fields. Mycorrhizal infections in roots of field-grown lilies were sparse and presumably young in March and gradually increased in size and number until September when bulbs were harvested. Over 75% of each root system became infected with mycorrhizae in fields with all four fungal species, and those levels were reached by July. In fields with only two mycorrhizal species, usually 50% or less of each root system was infected, even by the end of the growing season.


Hyphal interference by Trametes hispida. The antagonistic activity of Trametes hispida Bagl. in dual culture with Hirschioporus species and other non-basidiomycetous fungi is interpreted as hyphal interference. Hyphae of T. hispida grow into and over colonies of sensitive fungi. Contact with hyphae of T. hispida results in cessation of growth and rapid necrosis of affected cells. Ultrastructural studies of the affected hyphae of Hirschioporus pargamenus (Fr.) Bond. & Sing. showed an early formation of extraplasmalemmal wall deposits, disruption of membrane systems, coagulation of cytoplasm, localized dissolution of walls, and loss of cell contents without penetration by the antagonist.


Anaerobic degradation of cellulose by mixed culture. A mixed culture in which cellulose is capable of being converted to methane and carbon dioxide was obtained from an inoculum procured from a sewage-treatment plant and maintained in a synthetic medium containing tissue paper and an inorganic salt and vitamin mixture. The culture was tested for its ability to degrade 12 different paper and cotton products under batch conditions in 3-l anaerobic fermenters. This culture degraded 6-8 mmol/l per week of cellulose, expressed as glucose equivalents, with total gas yields of 0.3 m3/kg of cellulose degraded. The gas produced contained between 56 and 59% of methane. Maximum cellulose degradation occurred at chemical oxygen demand:nitrogen:phosphorus level of 80:5:1 and was adversely affected by high stirring rate. Also the presence of higher proportions of lignin in cellulose products adversely affected the ability of this culture to degrade cellulose.


The ability of some Yersinia enterocolitica strains to invade HeLa cells. Many types of Yersinia enterocolitica have been isolated from animal, environmental, food, and human sources but their public health significance remains uncertain. Seventy two strains of Y. enterocolitica were tested for their abilities to invade HeLa cells. The typical clinical strains invade HeLa cells like the other species of invasive pathogens. This characteristic remains even in old stock cultures and can be temperature-sensitive like the motility characteristic. With the use of electron micrographs it was demonstrated that the bacteria were truly intracellular and not merely adhering to the HeLa cell membrane. The esculin-and salicin-positive typical clinical strains did not invade HeLa cells. None of 34 food and water isolates were invasive by this test. The negative Y. enterocolitica strains did not adhere to the cells and cause ambiguous results. The HeLa cell test is simple, inexpensive, rapid, and should prove useful marker for screening the Y. enterocolitica isolates.


Ultrastructure of Nocardia-like variants of Mycobacterium smegmatis and chemical composition of the basal cell wall layer. Mycobacterium smegmatis, its orange-red--pigmented (OR) variants, and back mutant strains were examined by electron microscopy using ultrathin sectioning, negative or positive staining, and freeze-fracture-etching methods. The parental and back mutant strains showed almost identical ultrastructures. Specifically, thick ramified fibers measuring about 15 nm in diameter were always visible in the positively stained cell wall, although they were not readily visualized with negative staining or freeze-fracture-etching. In contrast, the cell walls of OR variants contained fibrous networks measuring about 11 nm in diameter, which could be observed by positive and negative staining as well as freeze-fracture-etching. Although cytoplasmic structures appeared similar among the four strains examined, mesosomes were significantly more abundant in the OR variants. The basal layer of the cell wall obtained as a phenol residue consisted of a dense membranous matrix containing scattered fibrous structures in the parental and back mutant strains, and fibrous networks in the OR variants. Chemical analyses showed that the basal layers of all four strains contained the same neutral sugars, amino sugars, and amino acids, i.e., arabinose, galactose, muramic acid, glucosamine, alanine, glutamic acid, and diaminopimelic acid. The alpha-branched, beta-hydroxylated fatty acids contained in the basal layers differ among the four strains, however, with nocardomycolic acids being present in the OR variants and mycolic acids in the parental and back mutant strains. Our previous conclusion that OR variants of M. smegmatis have characteristics similar to those of nocardia is supported by the present study.


Vascular amyloid in the aging central nervous system. Clinico-pathological study and literature review. The clinico-pathological features of five patients with vascular amyloid restricted to the central nervous system are presented. In three normotensive patients, intracerebral hemorrhage was the dramatic manifestation of amyloid angiopathy. In two other cases, one of amyloid in an arteriovenous malformation, the other of amyloid following therapeutic radiation, amyloid deposition was asymptomatic. Clinically, amyloid angiopathy must be considered in the different diagnosis of intracerebral hemorrhage, independent of the presence of dementia. Pathologically, a factor common to the syndrome of cerebrovascular amyloid appears to be locally increased vascular permeability resulting from a variety of previous tissue injuries.


Cerebral hemodynamics in migraine.

Cerebral hemodynamics in migraine. Clinical and angiographic findings in migraine are briefly reviewed in relation to cerebral hemodynamic changes shown by regional cerebral blood flow (rCBF) studies. Three cases of migraine studied by the intracarotid xenon 133 method during attacks are reported. In classic migraine, with typical prodromal symptoms, a decrease in cerebral blood flow has been demonstrated during the aura. Occasionally, this flow decrease persists during the headache phase. In common migraine, where such prodromata are not seen, a flow decrease has not been demonstrated. During the headache phase of both types of migraine, rCBF has usually been found to be normal or in the high range of normal values. The high values may represent postischemic hyperemia, but are probably more frequently secondary to arousal caused by pain. Thus, during the headache phase rCBF may be subnormal, normal or high. These findings do not exclude the possibility of distension of the larger intracranial arteries during migraine headache, but the angiographic evidence, however limited, does not support this speculation.


Pure spastic paralysis of corticospinal origin. This presentation includes six cases of chronic bilateral pure motor hemiplegia, one of these with pathological findings; one clinical case of chronic pure motor quadriplegia and one pathologically-studied case of chronic pure motor paraplegia. These cases may illustrate a spectrum of pure corticospinal disorders that heretofore has not been fully recognized.


Lumbo-sacral radiculopathy induced by radiation. Two patients had lumbo-sacral radiculopathy following radiation treatment of cancer. Twenty previously reported cases were similar. The clinical picture is one of progressive motor and sensory loss in the legs, usually appearing within a year after radiation, but sometimes delayed up to several years. Experimental studies quoted indicate greater vulnerability of peripheral nerves to ionizing radiation than has been previously recognized. Lumbo-sacral radiculopathy is readily produced in the experimental animal (rat) and affords an experimental model closely resembling the human cases reported.


A community neurologist's personal viewpoint on neurological training. A study of 200 patients referred to a community neurologist showed that 87.5% of the patients were seen in the office and only 12.5% in hospital. Neurological signs were present in 52% and 28.5% had neurological signs which materially affected the diagnosis. A questionnaire sent to several teaching centers showed that only one center sent students and residents to community neurologists' offices at all and in most centers the resident spent just 10 to 20% of his time seeing out-patients. It was felt that the balance of in-patient/out-patient teaching for students and residents was wrong, and that more emphasis should be placed on the neurological history than on the examination. Proposals are made to involve the community neurologist as well as the academic neurologist in the training of students and residents which would benefit all four groups.


Central nervous system vasculitis in rheumatoid arthritis. The history of a patient with rheumatoid arthritis and necrotizing vasculitis affecting only the central nervous system is reported. Clinical and pathological involvement by this process was present in both cerebral hemispheres, the pons and spinal cord. Review of the literature revealed that cerebral vasculitis in rheumatoid arthritis has been reported rarely and spinal cord vasculitis not at all.


Afterdischarge thresholds and kindling rates in dorsal and ventral hippocampus and dentate gyrus. Electrodes were implanted to dorsal hippocampus (CA1), ventral CA1, DOrsal dentate gyrus or ventral dentate gyrus. Epileptiform afterdischarge (AD) thresholds were lower in dorsal areas than in ventral areas. Dorsal areas, however, required a greater number of stimulations to develop ("kindle") a fully generalized convulsion than did ventral areas. Thresholds and kindling rates in the dentate gyrus were intermediate between dorsal and ventral CA1, except for the ventral dentate which had higher AD thresholds than ventral CA1. Secondary sites within the hippocampus subsequently kindled within a few stimulations following completion of kindling in the primary site, regardless of which hippocampal area served as the primary site.


A two-dose dexamethasone suppression test in patients with psychiatric illness. After exposure to a low and high dose dexamethasone regime, 11 of 34 acute psychiatric inpatients demonstrated abnormal dexamethasone suppression characterized by morning and/or mid-afternoon escape from suppression. This abnormality of suppression was found in primary depression, in mania, and in acute schizophrenia. In primary depression, the presence of abnormal dexamethasone suppression failed to discriminate "endogenous" depressed from "other depressed" subjects. Because nonsuppression to a high dose of dexamethasone is also found in patients with ectopic ACTH secretion and in patients with autonomous adrenal tumors, caution is necessary in the interpretation of nonsuppression which persists after recovery from psychiatric illness. As patients with Cushing's syndrome of uncertain etiology may be referred to a psychiatrist for a diagnostic evaluation, the psychological correlates of abnormal dexamethasone suppression need to be established with greater certainty.


Responses to moral dilemmas in medical students and psychiatric residents. There has been an increasing interest in the area of medical ethics as indicated not only by the recent proliferation of books and articles but also in the re-emergence of crucial moral issues such as euthanasia, abortion and the like. The difficulty with the existing literature is that these reports are often descriptive, anecdotal and situationally relative to the decision maker. In this study, the authors utilized a cognitive developmental approach to studying responses to moral situations not only because this approach is cross-culturally universal but also because it is not subject to situational variables. In this regard, the results of the assessment of medical students and psychiatric residents are presented as well as a comparison of moral reasoning stages in relation to the C.M.A. Code of Ethics. Recommendations for further research are presented.


Two new cases of XYY chromosome complement: and a review of the literature. Two cases with XYY chromosome complement are presented and compared with 153 cases described in the literature. Some patients with abnormalities of personality development and manifest psychopathology may have sex chromosome abnormalities and should be studied further for the interaction of genetic and environmental factors in personality development. In particular, tall, schizoid impulsive men with a history of criminality, arson or sexual offences should be screened for this particular genetic configuration. Because of the biased manner by which most of the cases are found, it is not yet known whether an XYY genotype results in a characteristic phenotype. What is needed is a genetic study of a normal population and a prospective study of newborns with various genotypes which would, unfortunately, create complex research and ethical problems.


Pharmacokinetics of the absorption, distribution, and elimination of melphalan in the dog. [14C]melphalan ([14C]L-PAM) was rapidly absorbed from the gut of dogs after oral dosing and reached a maximum concentration in the serum by 30 minutes. The disappearance of L-PAM (intact drug) from the serum was biphasic after iv administration, with half-lives of 14 and 66 minutes for the alpha and beta phases, respectively. The urinary excretion accounted for 44% of the total radioactivity and 25% appeared in the feces. Approximately 8% of the dose was excreted unchanged in the urine. Biliary excretion was rapid, with 11% of the dose being accounted for in the bile after 30 minutes; approximately 80% of these drug equivalents (materials containing radioactivity) was parent compound. Since large amounts of L-PAM appeared in the bile, the agent may prove to be active against cancers of the gall bladder, bile ducts, and duodenum.


Some observations on the human pharmacology of methotrexate. Plasma and urinary levels of methotrexate (MTX) have been measured enzymatically in 18 patients receiving doses of 5-1250 mg. When tritium-labeled MTX was administered, plasma levels measured by radioisotope counting were significantly higher than those measured enzymatically, the difference being accounted for by the presence of tritium label in plasma water as a result of drug metabolism. Renal clearance of MTX correlated well with glomerular filtration rate (GFR) and was consistently lower than the GFR, suggesting tubular reabsorption of the drug at the rate of urine flow studied. Plasma clearance measured by an infusion method was consistently greater than renal clearance, suggesting drug metabolism. Biliary MTX levels have been measured in three patients and are very much higher than plasma levels, suggesting a quantitatively important biliary recirculation of the drug. Plasma levels of MTX measured after 24 hours were not significantly different following iv or im administration, but were higher if an infusion was used.


Chemotherapy for metastatic carcinoid tumors: experiences with 32 patients and a review of the literature. An analysis of results of chemotherapy in 32 patients with metastatic carcinoid tumors was carried out. The most frequently used chemotherapeutic agent was 5-fluorouracil (5-FU) followed by nitrosoureas in combination with 5-FU or with cyclophosphamide. Adriamycin (used as adriamycin-DNA complex) alone or in combination with other drugs was used in seven patients. Seven partial responses were observed, five of them occurring in the patients receiving adriamycin-containing regimens. Based on these findings, adriamycin deserves further evaluation in metastatic carcinoid tumors.


Ultrastructure of the heart muscle cells of the cuttlefish Rossia macrosoma (Delle Chiaje) (Mollusca: Cephalopoda). The muscle cells of the ventricle, the branchial heart and the branchial heart appendages of Rossia macrosoma (Delle Chiaje) are studied. The ventricle myocardium has three muscle layers, while the other two organs exhibited a loose arrangement of muscle cells. The muscle cells of the ventricle, the branchial heart and the branchial heart appendages are similar in structure. The nuclei are surrounded by myofibrils. In the myofibrils A-, I- and discontinuous Z-bands are seen. The diameters of the thick filaments are 300--400A, their length varies from 1.7 to 3.9 mu. Thin filaments have a diameter of approximately 85A. The ratio between thick and thin filaments is roughly 1 to 11. The SR runs mostly as a longitudinal network within the myofibrils. A few short T-tubules are observed in the Z-regions. Peripheral and internal couplings exist. The latter are few in number. Intercalated discs are small and rarely observed. They have been found in all three organs. A difference in the function of these organs is not reflected in the ultrastructure of the intercalated discs. These discs are often of the interdigitating type with interfibrillar junctions and unspecialized regions. Peripheral couplings are seen at the unspecialized regions. The intercalar surfaces of the muscle cells "shoulder off" into the lateral surface, and the transition between the two surfaces is not a sharp one. Attachment plaques are found scattered over the whole sarcolemma.


The role of the subfornical organ in drinking induced by angiotension in the Japanese quail, Coturnix coturnix japonica. Synthetic 5-valine angiotensin II (AII) induced copious drinking when applied directly to the the subfornical organ (SFO) in the Japanese quail. Reliable response was obtained with as little as 1 ng of AII. The amount of water intake increased dose-dependently from 5 ng to 1 microgram. A latent period of 73.0 +/- 11.0 seconds at 100 ng was noted. The electrical destruction of the SFO significantly reduced the amount of water intake induced by both intravenous and intracranial AII injections. The decrease was proportional to the extent of the SFO lesion. It is conceivable, therefore, that the SFO plays an important role in elicitation of drinking by AII in birds as suggested in mammals.


Modification of Drosophila cell surfaces by concanavalin A. The effect of Con A on the surface morphology of cultured cells of Drosophila melanogaster growing on coverglasses was examined by scanning electron microscopy. With low lectin concentrations (5--10 microgram/ml) surface filaments disappeared and the cells flattened and spread against the glass surface. Cytoplasmic fusion bridges were observed in areas where cells made contact. Concentrations of Con A ranging between 50--500 microgram/ml caused cell shrinkage and surface distortions without cell flattening and filament loss. These morphologic effects were not apparent if Con A binding sites were blocked by preincubation with alpha-methyl-D-mannopyranoside before application to the cell cultures. However, once the Con A-mediated changes were in effect, the cells failed to show recovery when they were returned to growth medium and a majority of the cells on the coverglasses degenerated. Presumably the cells whose morphology appears unaffected by Con A treatment are the survivors that repopulate cultures returned to growth medium.


Ultrastructure of lateral line organs in aneurogenic amphibian larvae (Ambystoma). An ultrastructural study was performed to determine the ability of presumptive lateral line tissue in A. maculatum embryos to migrate and differentiate in the absence of all sensory innervation. In experimental animals, all presumptive neural tissue was surgically removed at Harrison's stage 24, leaving only the posterior portion of the post-auditory placode. At later stages, completely differentiated aneural lateral line organs were found in the midbody region of the larvae. These were morphologically similar to those of control larvae. No signs of atrophy or degeneration of the neuromasts were seen even after several weeks of nerve-free conditions.


Ultrastructural changes in the mitochondria of brown adipose cells during the hibernation cycle of Citellus lateralis. The mitochondrial structure in the brown adipose cells of the golden mantled squirrel, Citellus lateralis, was examined throughout the year in biopsy samples. The mitochondria showed remarkable and apparently reversible changes in size and internal structure related to the physiologic activity of the animal. In the active animal the size of the largest mitochondria was 2.4 micrometer X 1.5 micrometer; during hibernation it increased to 7 micrometer X 2.5 micrometer; and during arousal it reached 11.2 micrometer X 5.3 micrometer. The cristae of the mitochondria in the brown adipose cells of the animals in hibernation phase formed loops, whorls and mesh-like interconnections. During the arousal phase they underwent further configurational changes. The most remarkable structure was associated with mitochondria of most unusual proportions which by dissolution gave rise to a new generation. This was a common finding during arousal but did not occur in any other phase of the hibernation cycle. The new mitochondria were virtually indistinguishable from those of brown adipose cells of any active animal.


An ultrastructural classification of the neuronal cell bodies of the rat dorsal root ganglion using zinc iodide-osmium impregnation. Zinc iodide-osmium (ZIO) impregnation of rat dorsal root ganglia differentially stained various elements in the neuronal cells, particularly their Golgi bodies. On the basis of this differential ZIO staining dorsal root ganglion neurones have been classified into seven types. The ultrastructure of these is described and the numbers of each type in the L4 dorsal root ganglion have been determined. Prolonged nerve stimulation did not change the relative numbers of the different cell types suggesting that none of the differences between cell types represents differences in their state of activity. The possibility is discussed that differences in morphology may reflect differences in neurotransmitter function.


The human vocal cord surface.

The human vocal cord surface. The epithelium of the vocal cord from children and adults is analysed with SEM and TEM. Scanning micrographs show that the apical cell membrane is furnished with microvilli and microridges of various patterns. The function of microridges is discussed in relation to the distribution and retention of mucus on the vocal cord.


Variable patterns of actin filaments in mammalian skeletal muscle. The ultrastructural organization of myofilaments in skeletal muscle was studied in four mammalian species (mouse, rat, hamster, goat). In all these species, myofibrils showing irregularly distributed arrays of a variable number of actin filaments (from 6 to 11) were observed. The proportion of such myofibrils and the predominant patterns of actin filaments varied from one species to another. These results are in agreement with those previously reported for human skeletal muscle.


Testicular involution following optic enucleation: the Leydig cell. The testes of Syrian hamsters underwent pronounced involution within six weeks after blinding. The seminiferous tubules were devoid of all stages of spermatid development and mature spermatozoa were absent from the tubule lumina. The diameter of of the Leydig cells was 25% less than that of controls. Examination with the electron microscope revealed thick bundles of collagen fibrils interspersed between Leydig cells and surrounding Leydig cells in the blinded hamsters. The Leydig cell nuclei were shrunken and highly infolded. Lipid droplets that were often seen in normal Leydig cells were absent in the involuting Leydig cells. The size of the Golgi complex and the amount of smooth endoplasmic reticulum were reduced. Results of the present experiment confirm that inactivity of the Leydig cells is the reason for the decline in serum testosterone levels in blinded hamsters.


Ultrastructural study on hepatic melanin in Xenopus laevis. The livers of Xenopus laevis, grouped by chronological age (0.5, 2 and 3 yrs), were studied electron microscopically. Ultrastructurally most of the melanin granules in the mature female liver showed an internal structure similar to the melanin granules of the oocytes. The hepatic melanin granules of immature females and of all males were pleomorphic and failed to show the characteristic internal structure similar to those of the oocytes. The oocyte is the probable source of most of the hepatic melanin of the mature female.


Fluorescence and ultrastructural localization of aminergic neurons in the nerve cord of Eisenia foetida (annelida--oligochaeta). The aminergic nature of the CV neurons present in the genital segments of the nerve cord of Eisenia foetida is demonstrated by fluorescence microscopy and by the chromaffin reaction modified for electron microscopy.


Germ cell proliferations in the fetal horse ovary. During the 340 day pregnancy of the horse, the germ cells in the fetal ovary showed a meiotic prophase which began in days 60-70 and might be prolonged after day 200. Three or four successive oogonial mitotic proliferations passed into the meiotic prophase but the great majority of the oocytes first involved degenerated, and no appreciable numbers of primordial follicles were left behind. At 150 days of pregnancy and again at 197 days, oocytes in early meiotic stages filled the ovarian cortex. Primordial follicles were present, but rare. As the prophase gradually came to an end, groups of oocytes became enclosed by small 'boundary' cells which formed in the stroma. Coalescence of these groups led to the appearance of coiled and branching formations containing small and large oocytes. Many of the original groups, however, contracted and became narrow strands and these persisted until the end of pregnancy, many oocytes disappearing from them, while others eventually developed in primordial follicles.