The effects of Corynebacterium parvum and surgery on the Lewis lung carcinoma and its metastases. The effects of Corynebacterium parvum on the mouse primary Lewis lung carcinoma and its metastases were studied. C. parvum was given at the same time as subcutaneous inoculation of tumour or in combination with surgical excision of the primary after 10 days' growth. When intravenous C. parvum was given at the same time as tumour there was a reduction in the primary tumour growth rate. There was a similar reduction in growth if the drug was given intravenously 7 days after tumour inoculation. Intraperitoneal and subcutaneous administration of C. parvum had no effect on the primary tumour. The number of pulmonary metastases were significantly reduced after intravenous or intraperitoneal C. parvum given at the same time as tumour. When C. parvum and surgery were combined and C. parvum was given not more than 2 days before operation there was only a slight reduction in metastases, but when the injection was given intravenously or intraperitoneally 3-4 days before operation the number of metastases was significantly reduced. Subcutaneous administration of C. parvum had little effect on metastases. There was no difference in the number of metastases in C. parvum-treated mice were killed after 21 or 28 days. C. parvum given on the same day as surgery was more effective if tumour excision was performed before day 10 when the metastases were less well established. It was concluded that in well-defined conditions C. parvum is effective against metastases of the Lewis lung carcinoma.


Colitis and diarrhoea: a problem with antibiotic therapy. During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis.


Fatal pseudomembranous enterocolitis following clindamycin therapy. A fatal case of pseudomembranous enterocolitis following oral and parenteral clindamycin therapy is presented. Interesting features in this case are involvement of the small bowel and complete sparing of the large bowel distal to a defunctioning transverse colostomy. The significance of the absence of disease in the defunctioned bowel is discussed in terms of aetiology and diagnosis of pseudomembranous enterocolitis.


Distal colomyotomy: follow-up of 37 cases. The 3-7-year follow-up results of 37 patients undergoing the operation of distal colomyotomy are reported. Twenty-five underwent surgery for uncomplicated diverticular disease; there was no mortality but 40 per cent of patients had recurrent symptoms. Twelve patients underwent surgery for complicated diverticular disease, with an operative mortality of 16-6 per cent and a recurrent symptom rate of 37-5 per cent.


Typhoid ileal perforations: why such mortalities? The average mortality of 25 per cent in typhoid perforations of the ileum treated operatively could be reduced, because only half of the cases die of the lethal complications of myocarditis and toxaemia. The results of the present study show important differences between the preoperative fluid and electrolyte therapy of survivors and non-survivors as well as differences in the urinary output per hour. The perforation-operation interval as well as duration of the illness also have prognostic significance. The problem of enteric fever must ultimately be solved by preventive measures, but the results of this review indicate that attention to these factors could halve the present mortality.


A retrospective analysis of the accuracy of immediate frozen section diagnosis in surgical pathology. An evaluation of the accuracy of 3556 frozen section diagnoses over a 10-year period has been carried out. The overall accuracy rate was 97.4 per cent, with umimportant discrepancies present in a further 1.8 per cent. In only 28 cases (0.8 per cent) was a false negative or positive diagnosis of malignancy made. Of these, 4 patients underwent an unnecessary radical operation, while in 9 patients further surgery had to be carried out at a later date. The essential accuracy of the frozen section technique is confirmed.


Intermittent non-sterile self-catheterization. Fourteen patients suffering from voiding disorders of various aetiologies were taught the art of intermittent self-catheterization. The rationale of this form of treatment is discussed and it is suggested that this regime may play a useful role in the management of patients who are not amenable to surgery or other forms of treatment.


Cancer prognosis predicted by preoperative lymphocyte responsiveness in vitro. The prognosis in cancer patients was studied in relation to their preoperative cell-mediated immune status. Thirty patients with various types of operable cancer were studied. Transformation of the lymphocytes in response to phytohaemagglutinin (PHA) in vitro was measured preoperatively. All the patients were followed up for 3 years. Those with normal preoperative lymphocyte responsiveness had a far better prognosis than those in whom this test was subnormal.


Assessment of portasystemic shunt patency by estimation of D-xylose excretion. The D-xylose excretion test appears to be a useful method of monitoring shunt patency after a portasystemic venous anastomsis for portal hypertension. A 5-hour urinary excretion greater than 6 g appears an acceptable indicator that the shunt is patent. A second criterion of patency is an increase of 4 g or more over the result of preoperative tests. If the excretion rate falls in the postoperative period or remains less than 4-2 g/5 h, the anastomosis may be assumed to be occluded.


A comparison of operative cholangiographic technique. The accuracy and postoperative morbidity of cannulation of the cystic duct in routine operative cholangiography were compared with those of needle puncture of the common bile duct. The results are comparable and a case is made for the simpler procedure of needle puncture of the common duct.


An experimental evaluation of the types of material used for bile duct drainage tubes. A comparison has been carried out of the properties of latex, silicone, red rubber and polyvinyl chloride (PVC) T tubes draining the common bile duct in dogs. The tubes remained in the animals for 15-98 days. Bile cultures, liver function tests, cholangiograms and the histology of the common bile ducts were studied, and the changes in the physical properties of tubes implanted in the experimental animals, and of those after 1 month's incubation in human bile, were assessed. The elasticity of the tubes was also measured and the tissue reaction around them observed. Finally, the tissue reaction following implantation in mice of tubes which had been incubated in human bile for 1 month was investigated, and compared with that when new tubes were used. Polyvinyl chloride tubes caused the least reaction in both the common bile duct and the peritoneal cavity. However, the lack of tissue tract formation around them, owing to their inertness, and their rapid development of rigidity make them unsuitable for use in biliary surgery. Red rubber tubes were found to be the most irritant. While silicone tubes proved to have desirable physical properties compared with latex tubes, they did, however, disintegrate easily with improper handling on suturing and were slow to produce a satisfactory tract, the latter fact suggesting that they would be unsuitable for short term biliary drainage. It appears that the latex tube is the tube of choice for drainage periods of up to 3 months, while silicone tubes are preferable when intubation for longer periods is necessary. Red rubber tubes may be the alternative for routine short term drainage if a latex tube is not available.


Spontaneous perforation of the common hepatic duct. A case of spontaneous calculous perforation of the common hepatic duct is presented. The late result of duct repair, that of stricture formation, is illustrated.


Double intussusception of the small bowel through a patent vitello-intestinal duct. A case of double intussusception through a patent vitello-intestinal duct is reported. The rarity of this condition is the reason for this short report.


Bilharzial polyposis of the rectum and sigmoid colon. The case is reported of a 10-year-old boy who had severe diarrhoea with blood and muscus for 1 year which was found to be due to bilharzial polyposis of the rectum and sigmoid colon. He was treated first with antibilharzial drugs. Later, because of multiple polyps and secondary infection, local surgical resection was performed.


An instrumental method of performing Lord's procedure for haemorrhoids. An instrument has been designed for carrying out Lord's procedure in the treatment of haemorrhoids. This permits standardization of the procedure with less likelihood of mucosal trauma. The inflatable dilator is covered by a disposable plastic cover. The efficacy of the instrument has been established.


Outpatient treatment of haemorrhoids by cryotherapy. The treatment of haemorrhoids by cryosurgery is fairly new. One hundred cases have been analysed and the results presented as a preliminary report. Although the maximum follow-up is only 18 months, so far the results have been encouraging, and should they be maintained this method of outpatient haemorrhoidectomy could dramatically alter the management of this condition.


Congenital absence of the vas deferns.

Congenital absence of the vas deferns. A case is presented of congenital absence of the left vas deferens, kidney and ureter, and the literature relating to this anomaly is reviewed.


Factors determining the rate of disappearance of sperm from the ejaculate after vasectomy. The relative importance of age and frequency of coitus in determining the time needed for the semen count to become negative after vasectomy was studied in a group of 831 men. Irrespective of the frequency of coitus, there was a highly significant positive correlation between a patient's age and the time taken to become aspermic. This has implications for general practice: the older patient should be warned that he will take longer than a younger man to become sterile.


Fournier's gangrene: a report of 5 cases. A report of 5 cases of infective gangrene of the genitalia and adjacent tissues occuring within a 1 1/4-year period is presented. Of these, 4 cases occurred within 5 months. All the patients were adult males. During the same period no similar pathology was observed in any female or child. Such a large number of cases occuring in so short a time is intriguing but we are unable to explain it. The treatment in all cases was with general supportive drugs, blood transfusion when needed and specific antibiotics. Local excision of the dead tissues and dressing with hydrogen peroxide and eusol gave satisfactory results.


A report on missile injuries in Cyprus 1974. This paper details the experiences of the Princess Mary's Royal Air Force Hospital, Akrotiri (TPMH), during the last 6 months of 1974. TPMH was at that time a small hospital (120 beds) with a clinical staff of 17 situated in the south of Cyprus (fig. 1). The series comprises 71 patients injured by bullets, shrapnel, bomb-blasts or mines, drawn from British personnel, United Nations Forces and the local Cypriot military and civilian population, resulting from the coup d'état of 15 July 1974 and the subsequent Turkish invasion and air attacks. The casualties were often severely wounded beyound the capabilities of the local hospitals. They were mostly admitted during a 2-week period, but many required multiple operations extending over the next 3 or 4 months, and altogether 119 operations were carried out on 41 patients at TPMH. The organization of the limited resources of the medical, nursing and supporting staff is outlined. The correct treatment of missile wounds is emphasized. Resuscitation, wound excision, splintage and delayed suture or grafting are essential. Minimal morbidity and mortality are gained by a practised approach to the compounded results of violence.


Sternoclavicular joint enlargement following block dissection. The sternoclavicular joint may become enlarged subsequent to block dissection of the neck. It should be managed conservatively and does not require removal, although both clinical and X-ray appearances may give rise to suspicion of metastasis in the head of the clavicle. A hypothesis of the pathology of this unfamiliar condition is proposed.


Cryosurgical haemorrhoidectomy.

Cryosurgical haemorrhoidectomy. One hundred consecutive cases of haemorrhoids were treated by cryosurgery. The cryoprobe used is a convenient and simple instrument and gave a satisfactory result in 94 of the patients. The technique and complications are described. The patients were treated as outpatients, usually without anaesthesia.


Non-accidental injury in children: what we do in Derby. A scheme for dealing with cases of non-accidental injury in children in the Derby clinical area has been  operating since 1971. A stable team of doctors, policemen, and social workers deal with each case. The parents are told at once that battering is suspected, and the police and social services department co-operate closely in establishing the facts, supporting the family, and protecting the child. A psychiatric assessment of the parents may help social workers decide on the long-term care of the child, and the forensic physician is invaluable if the case has to go to court. The team has made three recommendations about prevention and management of these cases: a specialist social service team should be set up to deal with these children and regain the skills and knowledge lost when children's departments were abolished in 1971; babies should be routinely weighed naked in infant  welfare clinics; and juvenile courts should be able to order a psychiatric report on the parents in care proceedings.


Measurement of cardiac muscle relaxation in hypothyroidism. The isovolumetric relaxation time of the left ventricle (IRT) in 20 hypothyroid patients (133 +/- (SE of mean) 4 ms) was significantly longer than that in 23 normal subjects (95 +/- 3 ms). During a trial of thyroxine replacement the  IRT in 12 hypothyroid patients fell from 143 +/- 4 ms to 107 +/- 4 ms. The IRT seems to be a useful index of end-organ function in hypothyroidism.


Relation between blood pressure, weight, and plasma sugar and serum insulin levels in schoolchildren aged 9-12 years in Westland, Holland. In 2388 schoolchildren aged 9-12 years who took part in a study of cardiovascular risk factors in Westland, Holland, plasma sugar concentrations were found to be positively correlated with systolic and diastolic blood pressure, independently of weight. Serum cholesterol levels were also related to systolic blood pressure in boys, but much less strongly than plasma sugar levels. The relation between serum insulin and blood pressure, independent of plasma sugar, was weak. The relation between plasma sugar and systolic pressure existed for both sexes and regardless of whether measurements were made in the morning or afternoon; its association with diastolic pressure was weaker, and was not so consistent over all groups. These findings suggest that the relations between risk factors for coronary heart disease that exist in adults are already evident in childhood.


Growth, behaviour, and educational achievement of Jamaican children with sickle-cell trait. A longitudinal study of the mental and physical development of 200 children with normal haemoglobin and 21 with the sickle-cell trait was carried out in a small rural community in Jamaica. At about 2 and  10 years of age heights and weights showed no significant differences. At about 10 years of age classroom behaviour, sociability, and educational achievement were similar. The results suggest that the sickle-cell trait does not affect growth and mental development.


Comparison of intra-amniotic prostaglandin F2 alpha and hypertonic saline for induction of second-trimester abortion. The efficacy and safety of intra-amniotic prostaglandin (PG) F2 alpha (25 mg repeated in six hours) and hypertonic saline (200 ml 20% NaC1) were compared in an international multicentre randomised study organised by the World Health Organisation's prostaglandin task force. Both hypertonic saline and PGF2alpha were found to be effective in terminating second-trimester pregnancy. The main advantage of PGF2alpha however, was its greater efficacy, with significantly higher success rates in the first 48 hours. Out of 717 women given PGF2alpha 614 (85-6%) aborted within 48 hours; by 24 hours 439 (61-2%) had aborted, and by 36 hours 574 (80-1%) had aborted. Out of 796 women given hypertonic saline 641 (80-5%) aborted within 48 hours; however, by 24 and 36 hours, respectively, only 161 (20-2%) and 462 (58%) had aborted. Although PGF2alpha was associated with a somewhat higher frequency of minor side effects than hypertonic saline, notably vomiting and diarrhoea, these were within acceptable limits. Only 59 women (8-2%) in the prostaglandin group had more than four episodes of vomiting and 11 (1-5%) more than four episodes of diarrhoea. Ohter side effects occurred only occasionally. No difference was found between the two groups in the frequency of incomplete abortion or excessive bleeding.


Asthma deaths in Cardiff 1963-74: 90 deaths outside hospital. In a detailed study of factors associated with death from bronchial asthma outside hospital 90 patients were investigated. The fatal attack was typically short and was most likely to occur in patients with a long history. Deaths often occurred before effective medical help was obtainable, but occasionally the patient or the doctor underestimated the severity of the attack. Patients especially at risk were those recently discharged from hospital after a previous attack. These deaths might be prevented by better patient education, a self-admission service for selected asthmatics, and by doctors using objective measurements of severity of asthma for the control of treatment. The underuse of corticosteroids is an important factor associated with death.


A relation between HLA antigens and clinical features in patients with acquired valvular heart disease. Analysis of the HLA antigen patterns in patients with acquired valvular heart disease showed that antigens A29 and AW30/31 occurred more often in those patients whose valvular disease was not preceeded by a history of rheumatic fever or chorea. Patients with no rheumatic history but with antigen A29 or AW30/31 had clinical features that distinguished them from others with valvular disease--namely, (a) isolated mitral valve disease and (b) the need for surgery, often at an early age, after a relatively short duration of symptoms.


Explanations for weight loss after ileojejunal bypass in gross obesity. Twenty grossly obese patients underwent ileojejunal bypass operations. Measurements of calories lost in faeces showed that the malabsorption could not account for the weight loss. Furthermore, the malabsorption was not decreased two years after bypass, when weight was no longer being lost. Dietary restriction is therefore largely responsible for the weight loss and increased food intake for weight maintenance.


Prognosis and early management of birth injuries to the brachial plexus. Twenty-four cases of birth injury to the brachial plexus were seen in 21 infants over 15 years. Obstetric complications were common, and in 11 cases traction was needed to deliver the shoulders. Three out of every four arms fully recovered after exercises. Splints were not needed. Reconstructive procedures were performed on three permanently paralysed arms when the children were aged about 4. There was no way of predicting which patients would recover. The muscles supplied by the suprascapular nerve were paralysed in all patients, and this paralysis persisted in those whose arms failed to recover fully.


Reducing outpatient attendances.

Reducing outpatient attendances. Outpatient attendances can be reduced by indirect contact by letter and telephone; this frees the consultant to concentrate on patients attending for the first time. Such methods have not yet been fully exploited in the National Health Service.


Course of patients discharged early after myocardial infarction. Two hundred and seventy-one (76%) out of 358 survivors of infarction were discharged by the eighth hospital day, and 251 (93%) of them survived to six weeks after discharge. Six of the 20 patients who died between discharge and six weeks did so after readmission and 14 died as outpatients. All these patients who died at home had transmural infarction and four had diabetes. In inpatients successful resuscitation occurred mainly within the first 48 hours, with only three successful long-term results from all the patients who suffered arrest later. This suggests that more prolonged inpatient care would not have reduced the late mortality. These figures justify continuing with an early discharge policy for most patients, but coronary care should probably be more prolonged for patients with diabetes.


Comparative study of short-term recovery of mental efficiency after anaesthesia. Two common general anaesthetic techniques were compared to evaluate the time taken for the patient's mental efficiency to recover sufficiently for him to be escorted home after inguinal herniorrhaphy. Recovery in performance efficiency to at least 60% of the patient's own maximum is suggested as a criterion for discharge, and this needs a stay in hospital of seven to nine hours.


Study of reticuloendothelial phagocytic capacity in patients with cholestasis. The phagocytic capacity of the reticuloendothelial system was studied by the clearance from the plasma of microaggregated iodinated human serum albumin. About half of the patients with cholestasis showed impaired Kupffer-cell phagocytosis. The finding may be relevant to the occurrence of surgical complications in patients with obstructive jaundice.


Hepatitis B in retreat from dialysis units in United Kingdom in 1973. Public Health Laboratory Service Survey. A prospective study of hepatitis in over two-thirds of the dialysis units in the United Kingdom has continued since 1968. After the introduction of a control and preventive programme in 1970 there was a sustained decline in the incidence of hepatitis B to the low level of 0-3% among patients and 0-1% among staff in 1973--a greater than tenfold decrease in four years. Comparisons with data from other countries suggest that the almost complete elimination of hepatitis B from dialysis units in the UK was due to the preventive programme.


Out-of-hours calls in a Leicestershire practice. In one year, 920 "out-of-hours" calls were received by a partnership of three general practitioners working from a health centre in semi-rural Leicestershire. The partners on duty saw 588 patients. Out of 898 patients on whom information was available only 75 (8-5%) were referred to hospital, mainly as casualties. The results are compared with a study of deputising services, and it is concluded that a partnership covering its own out-of-hours calls can provide a more personal service and appears to make fewer demands on NHS resources.


High-dose corticosteroids in severe acute asthma. Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma.


Superficial carcinoma of the stomach.

Superficial carcinoma of the stomach. Nine cases of superficial gastric carcinoma have been detected with upper gastrointestinal endoscopy in Bristol in the past two years. This contrasted with only six cases found from postoperative gastrectomy specimens examined in the previous eight years. It is often difficult to distinguish a superficial carcinoma from a benign ulcer, and endoscopic diagnosis is effective only if multiple biopsy specimens are taken. Endoscopy should also be repeated and multiple specimens taken until the lesion has healed; even malignant ulcers may heal, and any healed area that is depressed with interrupted mucosal folds should be suspected of malignancy. The endoscopic and histological appearances, the age of the patients, and the clinical behaviour of the disease resembled descriptions of the disease, principally from Japan. Superficial gastric carcinoma is probably under-diagnosed in Britain.


Whole-body in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxycholecalciferol. Four selected adults with different patterns of osteodystrophy receiving regular dialysis were treated with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) 0-5-2 mug/day for 10 to 12 months. In two patients, one with osteitis fibrosa and the other with osteomalacia, significant biochemical, radiological, and histological improvements occurred, and total body calcium measured by in-vivo neutron activation analysis increased. In two patients, in whom there were no increases of whole-body calcium, neither biochemical improvement nor healing of bone lesions occurred during the study; in one of these patients the effect of 1-alpha-OHD3 on bone resorption may have contributed to loss of body calcium and deterioration of bone disease. 1-alpha-OHD3 may therefore be a valuable adjunct in the treatment of only some patients with renal osteodystrophy. Whole-body in-vivo neutron activation seems to provide a sensitive and non-invasive index of early response to treatment.


Headache after carotid endarterectomy.

Headache after carotid endarterectomy. Forty-eight hours after undergoing a successful right carotid endarectomy a patient complained of headache in and behind the right eye radiating to the temple and forehead. The onset of headache was sudden, and the pain was severe and throbbing. After three weeks of regular four- to eight-hour attacks each day the headaches gradually became less frequent. Two months after operation they had disappeared completely. Headache as a complication of endarterectomy is rare, but typically it is vascular and subsides spontaneously in one to six months. If a predisposition to migraine were a precipitating factor many more cases would be expected. No possible explanation for for headache after carotid prearterectomy can account adequately for its apparent rarity.


Programmed investigation unit.

Programmed investigation unit. The programmed investigation unit (PIU) is a inpatient unit where a full range of investigational medicine can be organised. It provides the basic minimum nursing care and is suitable for ambulant patients who can care for themselves. Requests for admission to the PIU at the Royal Victoria Infirmary, Newcastle upon Tyne, come directly from clinical units, and the staff of these units perform some of the tests and remain responsible for the patient while she is in the unit. At present the unit caters only for female medical patients. The average waiting time for admission is three weeks, and because the unit now deals with most investigations the waiting time for admission to the female general medical wards has fallen considerably. The staff of the unit have gained expertise in diagnostic methods, while the nurses of general medical wards have been free to concentrate on nursing those patients who need it. Separating patients who need investigations from those on general medical wards seems a logical way of using resources and staff to best effect.


Hypophosphataemic osteomalacia in patients receiving haemodialysis. Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started.


Immediate plasma renin response to propranolol: differentiation between essential and renal hypertension. The immediate short-term effect on plasma renin activity of intravenous injection of propranolol was studied in 31 normal subjects and 166 hypertensive patients. In patients with essential hypertension and normal subjects plasma renin activity fell considerably within 15 minutes; the fall was directly proportional to initial plasma renin levels. In contrast, in patients with renal hypertension the fall was much less pronounced or totally absent. These differences in response to propranolol provide, though presently only on a group basis, a biochemical means of differentiating between patients with renal hypertension and those with essential hypertension. The observations also indicate that, unlike normal subjects and patients with essential hypertension, in patients with renal hypertension sympathetic activity plays no part in the control of basal plasma renin levels.


Enhanced drug metabolism in cigarette smokers. The effect of cigarette smoking on salivary antipyrine disappearance rate, and as an index of hepatic drug metabolism, was studied in 42 healthy subjects. Antipyrine half life was significantly shorter in smokers compared with non-smokers. To determine whether this difference was due solely to tobacco consumption eight subjects were restudied two months after they stopped smoking. The mean antipyrine disappearance rate in this group increased by 23% in contrast to that of a control group, which did not alter. Cigarette smoking contributes to the considerable variation in interindividual rates of drug metabolism.


Adder bites in Britain.

Adder bites in Britain. Ninety-five cases of adder bite that have occurred in Britain over the past 100 years are reviewed. Most bites occurred in men who foolishly picked up the adder. Three-quarters of the victims reached hospital within two hours of the bite. When venom is injected the early symptoms include local swelling and discoloration, vomiting, diarrhoea, and early collapse, which often resolves spontaneously. In severe poisoning persistent or recurrent shock is the main feature. Children recover quickly but adults may take weeks or months to recover, during which there may be considerable disability in the bitten limb. Deaths are rare: only 14 deaths from poisoning were recorded in the past 100 years. In England and Wales only one death from adder bite was recorded in 1950-72, but there were 61 deaths from bee or wasp stings. In most cases simple symptomatic treatment is enough, but all patients should be carefully monitored. With persistent or recurrent shock Zagreb antivenom is indicated; and it should also be considered in adults seen within two hours of the bite to minimise morbidity from local effects.


The elderly mentally ill--whose responsibility? The elderly mentally ill make considerable demands on health and social services. To evaluate the need for these services a one-day census of all people aged 65 and over was carried out in an area containing 220 000 people (40 000 over 65). Data were obtained on the nursing needs and psychiatric state of the 2162 elderly people in hospital or local authority residential homes for the elderly, or living at home receiving care from the community nursing service. One-third were classified as having psychiatric problems, more than half of them being outside hospital. Residential homes and community nurses play a significant part in caring for the elderly mentally ill, and an integrated but flexible manpower policy is important.


Some characteristics of homosexual men.

Some characteristics of homosexual men. Although recognition of homosexuals is often important, many doctors lack the necessary skill or experience, so to assist them a group of 5,302 men was surveyed using a computer-based data system and 9-1 per cent. were recorded as homosexual. Analysis showed a relatively high proportion of homosexuals among men with syphilis and gonorrhoea, and a low proportion among men with nonspecific genital infection (non-specific urethritis and proctitis) and other infections. All men with secondary syphilis were homosexual. A relatively high proportion of men born in Eire, Spain, and North America were homosexual and a relatively high proportion of men living in the West End of London were homosexual. While these findings will be of most value to those working in STD clinics in London they may also be helpful to those working elsewhere and in other disciplines.


Changing pattern of male homosexual registrations in a venereal disease clinic, 1964-1974. Registrations of heterosexual and homosexual men, with and without gonorrhoea, as recorded at Ward 34, Newcastle General Hospital, from 1964 to 1974, show substantial rises. During this time, the number of cases of gonorrhoea in men, both heterosexually and homosecually acquired, has approximately doubled. However, the incidence of individual gonococcal re-infection would not appear to have changed significantly. More men attend with non-venereal conditions and show an increasing willingness to return. A greater co-operation between homosexuals with gonorrhoea and the social unit has evolved and a greater number of sexual contacts are now traced and examined.


Pharyngeal gonorrhoea in homosexuals.

Pharyngeal gonorrhoea in homosexuals. In a prospective survey of 106 male homosexuals, investigations included smears and cultures of material taken from the tonsillar areas. A diagnosis of gonococcal pharyngitis was made in six cases. This is the largest series so far reported from England. The prevalence of gonorrhoea nd less conventional sexual practices must prompt us to investigate gonococcal infection in sites remote from the ano-genital region.


Single oral dose of 1-5g. talampicillin in the treatment of gonorrhoea. 81 patients have been treated with single oral doses of 1-5 g. (6 tablets) of talampicillin without probenecid. The failure rate amongst those followed was only 4-2 per cent. No side-effects were reported. These results were superior to those obtained with 2-0g. or equivalent of ampicillin, amoxycillin, or pivampicillin with probenecid. Talampicillin is thus the most potent ampicillin-like antibiotic so far available for the treatment of gonorrhoea and is capable of curing the disease with a smaller single dose without probenecid than is necessary for other preparations.


Prostitution in Sheffield.

Prostitution in Sheffield. Prostitution in Sheffield, a city with over half a million population, has been reviewed in its legal, social work, and medical aspects. The years studied were 1960-73. The medical studies were confined to the years 1968-72. Prosecutions for soliciting increased steadily during the study period. The trend was more marked locally than nationally and was associated both with increased police activity and, more recently, with the pursuit of a socially-aware sentencing, probationary, and social work policy. During the 5-year medical study, sixty prostitutes were seen. Using gonorrhoea as an index they were found to hazard the health of both themselves and others. Recurrent infection was the rule amongst them and 40 per cent. suffered salpingitis. In epidemiological terms our findings show that the vector role of prostitutes continues undiminished. The alleged decline in their role is relative only and not real. They accounted for one in six of locally acquired gonococcal infections in heterosexual men. The study indicates the need for the regular monitoring of the social phenomenon or prostitution and for the detailed study of all its aspects on a national basis.


The effects of centrifugation on the morphology of the lateral vestibular nucleus in the rat: a light and electron microscopic study. Very little is known about structural changes in the central nervous system following exposure to increased g forces. Sprague-Dawley rats were centrifuged at Ames Research Center at 2.76-4.15 x g for periods ranging from 4 days to 21 months. The lateral vestibular nuclei were processed for electron microscopy and examined for evidence of structural alteration as a result of centrifugation. The number of filamentous nuclear inclusions, varicosities, and relative number of axosomatic synaptic terminals containing flattened vesicles (presumed inhibitory in function) increased in centrifuged rats. Altered mitochondria also were noted in that cell bodies of Deiters' neurons. Neuroaxonal dystrophy (NAD) was found in long-term centrifuged rats and was characterized by axons filled with reticulated mitochondria. The NAD found in the lateral vestibular nuclei of centrifuged rats is different from that seen in the dorsal column nuclei of aged mice.


Postnatal development of acetylcholinesterase in the caudate-putamen nucleus and substantia nigra of rats. The postnatal development of acetylcholinesterase (AChE, EC 3.1.1.7) and NADH-diaphorase was examined in the caudate-putamen nucleus and substantia nigra of rats ranging from 3 to 90 days in age. From 3 to 15 days post partum islands of AChE and NADH-diaphorase activity were observed in the caudate-putamen nucleus. Individual neuronal somata could also be seen in AChE-stained sections up to 15 days. At later ages neuropil staining became increasingly dense, and this presumably accounted for the infrequent visualization of cell bodies in the brains of older animals. During development AChE appeared in the caudate-putamen nucleus in a lateral to medial topographic order; analogously, enzyme staining in the neostriatum reappeared in the same lateral to medial topographic order in adult rats following irreversible AChE inhibition by intramuscularly injected bis-(1-methylethyl)phosphorofluoridate (di-isopropylfluorophosphate: DFP). Furthermore, DFP treatment in mature animals revealed the presence of AChE in striatal neurons having morphologies similar to those observed in newborn rats. A similar time-course of postnatal AChE development was observed in the substantia nigra. In both the pars compacta and pars reticulata individual cell bodies, which were visible at early ages (3-10 days), became increasingly obscured at later times after birth by extra-somata staining. Between the 6th and 15th postnatal days AChE-containing fibers were seen projecting apparently from pars compacta into pars reticulata. Comparison of the present results with histochemical data of other investigators on the postnatal development of monoamines indicated the likelihood of cholinergicmonoaminergic interactions in the neostriatum and substantia nigra.


Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously, the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity.


Ontogeny of leg motor output in the chick embryo: a neural analysis. The motor output of the leg of the chick embryo during hatching (20 days of incubation) was characterized using electromyographic (EMG) recordings from identified knee and ankle muscles. A highly coordinated pattern of motor output was found. It was therefore used as a standard against which to compare the motor output from younger embryos (7, 9, 13, 17 and 19 days of incubation). Despite large differences in some aspects of the EMG records from embryos of different ages, consistent patterns of muscle activation were observed. Quantitative analysis of phase and latency relationships between pairs of muscles indicated that at least some elements of the neural circuitry involved in generating the hatching motor output may be laid down very early in development. Duration vs. latency plots revealed that there is a gradual refinement in the temporal pattern of alternation between antagonist muscles during development.


Neuronal activity with relation to cardiac rhythm in the lower brain stem of the dog. Extracellular recordings of reticular neurons in the lower brain stem were performed in anesthetized dogs. Thirty out of 131 neurons showed rhythms of about 2-4 c/sec which were similar to heart or to EEG rhythms. By means of post-event-time histograms, correlations to the EEG delta-theta rhythm could be found in some neurons. These results were published elsewhere. Fixed relations of the neuronal activity to the cardiac rhythm could be verified in 7 neurons. Two neurons showed maxima 70 msec and 120 msec, respectively, after the beginning of the pulse wave. Two neurons showed minima after 110 msec and 130 msec, respectively. Three pulse-rhythmical neurons could not be classified in this way. This rhythmicity was changing or vanishing during the course of registration, but it could be strengthened experimentally by blood-pressure increase. It was shown that these neurons receive inputs from cardiovascular afferents and therefore are blood-pressure dependent neurons. From the finding that pulse-rhythmical modulation is different at different times under the same blood-pressure levels, it is assumed that there are varying strong influences from other systems to these neurons. The fact that these neurons are influenced by cardiovascular afferents does not mean, however, that they are cardiovascular neurons exclusively. It is suggested that blood-pressure reticular neurons may belong to the cardiovascular system as well as to other brain stem systems.


Metabolic regulations of the rhythmic activity in pacemaker neurons. III. Neutralization of the pentylenetetrazol effect in regularly beating Aplysia neurons by metabolic modifiers. In regular beating pacemaker neurons isolated from the sea hare Aplysia californica, 30-50 mM pentylenetetrazol (PTZ) induces spike doublets and triplets, multi-spike bursts, and paroxysmal depolarizing shifts. The development of the characteristic PTZ-induced changes in impluse pattern is preceded by a transient increase in discharge frequency and a reduction in after-hyperpolarization. According to earlier findings, the rhythmic spike activity of pacemaker neurons is governed by a phosphofructokinase-fructose-1,6-diphosphatase-mediated substrate cycle, the activation of which leads to the appearance of spike bursts. Inhibitory modifiers of this neuronal substrate cycle, such as citrate, ATP, and 3-phosphoglycerate, are able to neutralize the changes in the impluse characteristics occurring as the result of PTZ action. Since the reinitiated single-spike trains reverted again to the PTZ pattern following the further addition of activating modifiers, such as fructose-1,6-diphosphate or fructose-6-phosphate, it appears likely that PTZ exerts an influence on the metabolic reactions driving the rhythmic spike activity. In contrast to the reversible effects of the metabolic modifiers the conventional anti-convulsants, phenobarbital and pentobarbital, merely block all spike activity.


Eye movements evoked by superior colliculus stimulation in the alert cat. (1) The electrical stimulation of the superior colliculus (SC) in the cat evokes exclusively conjugate and contraversive eye saccades. (2) Their maximum velocity is markedly higher than that of spontaneous saccades. (3) The stimulus parameters (intensity, frequency, pulse width) have but little effect on the characteristics of the saccades. (4) In the anterior half of the SC, corresponding to the projection of the 12-15 central degrees of the retina, amplitude and direction of saccades depend exclusively  on the position of the electrode. (5) In the posterior half, corresponding to the projection of the peripheral retina, saccades are 'goal directed' and the position of the goal is determined by the location of the electrode. (6) An increase in stimulus train length produces, in the anterior part, a succession of identical saccades and, in the posterior part, a goal fixation. (7) Taking all these data into consideration, a model of the foveation process in the cat is proposed.


Thermoregulatory responses to intraventricular norepinephrine in normal and hypothalamic-damaged rats. We examined the effects of intraventricular injection of low doses of norepinephrine (NE) on internal temperature and on behavioral and reflexive thermoregulatory responses in unrestrained rats. NE lowered the body temperature of the rats in cold and neutral environments but had little effect in the heat. The hypothermia was blocked by alpha-adrenergic antagonists but unchanged by beta-adrenergic antagonists. In the cold, the hypothermia was caused primarily by a lowered metabolic rate. At ambient temperature 25 degrees C, it was caused primarily by vasodilatation while metabolic rate increased. Thus, reflexive responses were not integrated to lower body temperature. Behavioral responding compensated for the hypothermia. In the cold, rats increased responding to get heat after NE. In a warm environment, they did not increase responding to escape heat. Thus, both reflexive and behavioral results support the idea that the set-point is unchanged after intraventricular NE. Wherever in the brain the NE may be acting, it is not in the preoptic-anterior hypothalamic area, because when this area was ablated, the hypothermia in response to intraventricular NE was greatly exaggerated.


Striatal afferent connections in the turtle (Chrysemys picta) as revealed by retrograde axonal transport of horseradish peroxidase. Horseradish peroxidase (HRP, 30% solution, 0.1-0.3 mul, 72 h) was injected unilaterally into the basal striatum (STR) and the dorsal ventricular ridge (DVR) of adult turtles (Chrysemys picta) in order to demonstrate the cells of origin of some afferents to these telencephalic structures. After selective STR injection, HRP-labeled cells were visualized in the dorsal thalamus and midbrain tegmentum, ipsilaterally. At thalamic level, HRP-positive neurons were located around nucleus rotundus, i.e., mainly within nuclei dorsomedialis anterior, dorsolateralis anterior and less abundantly in nuclei ventralis and reuniens. At midbrain level, a large population of labeled neurons was disclosed within the ventrolateral portion of rostral tegmentum. Other HRP-positive neuronal somata were found scattered throughout the lateral portion of the caudal midbrain tegmentum. In addition, labeled axons were visualized in both peduncles of the lateral forebrain bundle (LFB) after STR injection. The HRP-positive fibers of the dorsal peduncle of the LFB were followed up to the ipsilateral labeled thalamic cells where they appear to arise, whereas the HRP-containing axons of the ventral peduncle were traced down to the lateral midbrain tegmentum where they appear to arborize. Most of the HRP injections into the DVR were confined to the mediodorsal quadrant of the rostral half of the DVR. In such a case, a very large number of HRP-positive cells were disclosed within all thalamic nuclei surrounding nucleus rotundus, ipsilaterally. In addition, numerous labeled neurons were also found in nucleus rotundus itself and within nucleus reuniens. No HRP-positive cells were disclosed caudally to the meso-diencephalic junction after DVR injection.


The rodent neostriatum: a Golgi analysis. In the adult rodent, coronal sections of Golgi impregnations of the neostriatum display a compact segregation of axon fascicles, neuronal clusters, and dendritic bundles thus forming an areolar configuration. Isolated neurons are rarely seen. The dorsomedial region of the neostriatum appears free of axon fascicles and dendritic bundles. Horizontal and sagittal sections of the neostriatum show clusters of cells parallel to axon fascicles. The neurons exhibit spine-laden dendrites with an initial spine-free segment. Neonatal impregnations exhibit a different configuration. Neonatally, cells tend to cluster but there is no bundling of dendrites. Neurons are spine-free or have protospines on the soma and the dendrites, including the initial segment. Transition from neonate to adult configuration is discernible at about 15 days after birth. The neostriatum of carnivores exhibits a different structure from the rodent neostriatum. This difference is associated with a developed anterior limb of the internal capsule in the carnivore. The axon fascicle-free portion of the carnivore neostriatum lacks dendritic bundles and pallisades. Portions near the capsule with axon fascicles appear similar to the rodent neostriatum with dendritic bundlings and pallisading. Such findings emphasize the importance of total neuronal configuration (neuronal-architectonics) in morphologic analyses.


Trans-glial channel-facilitated translocation of tracer protein across ventral nerve root sheaths of crayfish. Trans-glial channels, which traverse the multilamellate glial sheath of crayfish nerves, are easily recognized in freeze-fracture preparations. Their structure and position in the glial layers of the sheath strongly supports the suggestion that they serve to facilitate rapid movement of molecules and fluids from outside the sheath to the surface of axons contained within. Segments of ventral ganglion nerve roots, which were ligated at their free ends, were immersed in crayfish Ringer solution containing 10 mg/ml horseradish peroxidase (HRP). Electron microscopic examination of the nerve sheath 30 sec after exposure to peroxidase showed that the protein had passed across the sheath and was present near the axon surface. Reaction product was present in trans-glial channels as well as in extracellular clefts and adaxonal tubular lattices thereby supporting the notion that these structures constitute a specialized conduit traversing the sheath. Often, 'fronts' of reaction product were observed across the sheath from its exterior to the interior reflecting a gradual accumulation of protein in extracellular clefts toward the axon. After 5 min in HRP-Ringer, protein appeared in all channels, extracellular clefts, and tubular lattices. With increased length of exposure of ligated nerve segments to HRP-Ringer, reaction product was found in vesicles in glial cytoplasm adjacent to axons. Results from this study suggest that trans-glial channels constitute an efficient system for rapid solute movement across nerve sheaths and may represent a mechanism whereby ions and nutrients are made available to nerves isolated in an avascular sheath.


The effect of subfornical organ lesions and ventricular blockade on drinking induced by angiotensin II. The role of the subfornical organ (SFO) as the unique receptor site for the drinking behavior induced by intracranial injections of angiotensin II (AII) was investigated. It was found that: (1) drinking in response to intraventricular (IVT) injections of AII was reduced in 6 rats but was unchanged after 80-100% damage of the SFO in 4 cases; (2) reduction of drinking to lateral ventricular application of AII was seen with no apparent SFO damage in 4 rats; (3) recovery of the AII induced drinking deficit was consistently observed within a short time interval (14 days), even in those animals with complete SFO lesions: (4) the presence of ventricular debris was correlated with deficits in water intake to IVT angiotensin injections. In a second experiment artificial blockade of the ventricular space was produced by a plugging technique. Plugging the anterior third ventricle simulated the effects of SFO lesioning. It was concluded that the SFO is not a unique receptor area since the ventral anterior third ventricle is also sensitive for AII (IVT) induced drinking. If the SFO is a receptor site for AII circulating in the CSF it is probably not the only periventricular receptor site. Access of AII to the anterior ventral third ventricle appears to be essential for inducement of drinking.


Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat. Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined.


[The Schmidt-Lantermann incisures of the myelin sheath of Mauthner axons: site of longitudinal myelin growth]. The myelin sheath of the Mauthner axons in the spinal cord of young and adult fish belonging to the family Cyprinidae was examined by phase and electron microscopy. The sheath thickened considerably with age, the number of lamellae increasing from 200-230 in young fish (length 2--4 cm) to 250-300 in adult animals (length 20-25 cm). During this growth, the myelin sheath remained fairly compact and of optimal thickness for impulse propagation, the axon/fiber thickness ratio being 0.67-0.72 in young and 0.76-0.78 in adult fish. As already observed by previous investigators, the Mauthner axons lacked nodes of Ranvier. However, Schmidt-Lantermann's clefts (SLC) were present at irregular intervals. Within the SLC, parallel arranged osmiophilic bands of variable length and with a thickness of approx. 42-44 nm were observed to form a transitional zone between the cytoplasmic areas of the oligodendrocyte and the typical myelin structure. Between such adjacent 'D-bands', which thinned out to build up the major dense lines, an electron translucent area measuring approx. 25--26 nm in width contained a thin 'I-band' (8--10 nm) which was continuous with the intraperiod line. It is speculated that, in the Mauthner axon, the SLCs may be sites where freshly synthesized myelin is added to the lamellae already present, thus permitting their longitudinal growth.


Ultrastructural changes in the developing nucleolus following axotomy. A large, basophilic, Feulgen-negative structure has been observed within the nucleoli of golden hamster facial motor neurons. This 'intranucleolar body' was seen, at the electron microscopic level,  to be composed of granules which are thought to be ribonucleoprotein particles. At 15 days postnatal age, this aggregation of granules had not yet be appeared. However, by 20--24 days, a small intranucleolar body had developed. At maturity, the intranucleolar body had a diameter of up to 2 mum. Facial nerve axotomy at 15 days did not appreciably alter the nucleolar morphology at 19 days; neither control (opposite side) nor experimental nucleoli contained intranucleolar bodies. Normal nucleoli developed intranucleolar bodies, however, between the ages of 20 and 24 days. After axotomy at 20 days and sacrifice at 24 days, a comparison of facial neuronal nucleoli demonstrated that while an intranucleolar body formed in the control, axotomy prevented this structure from forming at its normal time. Also, when the facial nerve of an adult hamster was axotomized and observed 4 days postoperatively, an intact intranucleolar body was not seen. Instead, the granular portions of the nucleolus appeared to have been dispersed into several small aggregates. We believe that the changes observed in granule distribution, both with development and after axotomy, are morphological indications of a qualitative and/or a quantitative change in rRNA synthesis.


Type 1 and 2 synaptic junctions: differences in distribution of concanavalin A binding sites and stability of the junctional adhesion. Two classes of synaptosomes have been distinguished in subcellular fractions from rat forebrain. They differ in morphology and distribution of concanavalin A binding sites. Morphological examination suggests that the two classes correspond to the type 1 (excitatory) and type 2 (inhibitory) synapses of intact brain tissue. Under the conditions of incubation employed in this study, type 1 synaptosomes show splitting of the synaptic junctions, but the type 2 junctions are apparently stable. The chemical differences illustrated by the differences in concanavalin A binding sites suggest that type 1 and type 2 synaptic junctions differ fundamentally in supramolecular structure rather than being superficial variants of basically similar structures.


Electrophysiological study on the postnatal development of neuronal mechanisms in the rat cerebellar cortex. (1) Functional commencements of the neuronal elements in the cerebellar cortex of young rats were studied electrophysiologically by means of laminar field potential analyses in the cortex on stimulation of the cerebellar surface (Loc) and the white matter (WM). (2) The antidromic action potential of Purkinje cells on the WM stimulation was observed at one day after birth. The climbing fiber excitation of Purkinje cells on the stimulation was noted at 3 days after birth. (3) The mossy fiber-granule cell synapses were found to function at 10 days after birth and the Golgi cell inhibition of granule cells could be proved at the same time. The excitatory action of parallel fibers and the inhibitory action of basket-stellate cells on Purkinje cells appeared simultaneously at about 12 days after birth. The transverse distribution across the cerebellar folium of the basket-stellate cell inhibitory action on Purkinje cells was found to be narrow up to 60 days after birth. (4) These results concerning the dates of commencement of excitatory and inhibitory synaptic actions in the cerebellar cortex were compared with those of synaptogenesis studied morphologically, and some implications of the dates in the functional development of the cerebellar cortex were discussed.


Visual receptive field types in the nucleus dorsolateralis anterior of the pigeon's thalamus. Extracellular recordings were made from cells in the dorsolateral thalamus (DLLv, DLLd, DLAmc) of the pigeon, and their receptive field properties analyzed with stationary and moving visual stimuli. One hundred and ten cells were classified as follows on the basis of their responses. I. On-center and off-center cells (56%). Most of the units in this class had a powerful inhibitory surround which decreased the activity generated at the field center and in some cases gave rise to firing when stimulated alone. II. On-off center cells (16%). These gave on-off responses to static stimulation. More than half of them had an inhibitory surround which suppressed both on and off discharge, or in other cases either the on or the off burst of the center response. This group of cells also responded strongly to motion independently of direction. III. Cells sensitive only to motion (28%). The discharges to movements of units in this class were not affected by the direction of motion. The visual properties of the thalamic units are discussed in conjunction with previous results in the optic tectum of the pigeon.


Differential effects of brain lesions on thirst induced by the administration of angiotensin-II to the preoptic region, subfornical organ and anterior third ventricle. (1) The possibility that water intake elicited by the administration of angiotensin-II to the preoptic region (POA), subfornical organ and anterior third ventricle is mediated by separate neural systems was investigated in 58 male Wistar rats using electrolytic lesion techniques. (2) Lesions of the midlateral hypothalamus and paramedial rostral midbrain produced a significant reduction in water intake to angiotensin-II microinjected into the POA but did not affect drinking following administration of angiotensin-II to the subfornical organ or anterior third ventricle. (3) Ablation of the midlateral hypothalamus, paramedial rostral midbrain, habenular nucleus or interpeduncular nucleus had no significant effect on water intake elicited in response to microinjection of carbachol or hypertonic saline into the preoptic region, subfornical organ or anterior third ventricle. (4) In a second series of 12 animals lesions of the subfornical organ attenuated water intake in response to a peripheral injection of renin or isoproteronol without disrupting drinking to peripheral administration of hypertonic saline or polyethylene glycol or to 24 h water deprivation. (5) It is concluded that separate neural systems mediate water intake elicited by administration of angiotensin-II to the preoptic area, subfornical organ and anterior third ventricle. The possible physiological significance of independent and parallel peripheral and cerebral renin-angiotensin systems for the control of drinking behavior mediated by angiotensin-II is discussed. (6) The present results are in agreement with previous work which indicates that water intake induced by central administration of angiotensin-II, carbachol and hypertonic saline is subserved by different neural substrates.


The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence dopaminergic pathway. Using the microdissection method of Palkovits and a sensitive microassay for dopamine (DA) and norepinephrine (NE), the CNS projections of the nigral A8, A9 and A10 dopaminergic cell bodies have been determined in rat brain. Following bilateral electrolytic lesions of the A8-A9-A10 region, DA levels fell significantly in the following areas: dorsal septal nucleus (85%), olfactory tubercle (75%), lateral amygdaloid nucleus (75%), habenula (75%), parietal cortex (75%), cingulate cortex (70%), cerebellum (50%), thalamic paraventricular nucleus (50%), and preoptic suprachiasmatic nucleus (45%). Of particular interest was the finding of a 40% fall in the dopamine levels of the median eminence after such lesions. Concentrations of NE in these same areas following lesions of the A8-A9-A10 region were unchanged. These findings suggest that the nigral A8, A9 and A10 dopaminergic cell bodies, project diffusely to many different areas of cortex, hypothalamus, and brain stem, and, more importantly, provide evidence for a previously unsuspected dopaminergic pathway from substantia nigra to median eminence, an area intimately concerned with neuroendocrine regulation.


Distribution of glutamate decarboxylase in discrete brain nuclei. The L-glutamate decarboxylase (GAD) levels of 70 rat brain nuclei were determined. The distribution of GAD is uneven. High AAD activity was found in the substantia nigra, the colliculi, some hypothalamic nuclei (e.g. dorsomedial) some nuclei of the limbic system (e.g. tractus diagonalis and accumbens) and the medial forebrain bundle. The reticular part of the substantia nigra had the highest activity, two-fold higher than any other nucleus. Low GAD activity was found in the nuclei of the pons, the hypothalamic median eminence and the reticular formation. Moderate activity was measured in most areas studied. The biochemical mapping of GAD is discussed in relation to possible GABA pathways in the brain.


The application of network analysis to the study of branching patterns of large dendritic fields. Network analysis of dendritic fields not only defines the topology and connectivity of segments of an arborescence, but offers a means of discovering how networks grow. An important theory has recently been formulated29 suggesting that dendritic branching patterns may be established by synaptogenic interaction of dendritic growth cones with growing axons. This thesis may be verified through network analysis since the theory predicts that growth at pendant vertices will predominate in dendritic networks, that dendritic growth will be directed into areas of maximal synaptogenic activity and that arc lengths will be inversely related, and the order of branching at vertices directly related, to the magnitude of the synaptogenic activity operating about growing dendritic terminals. The possibility of a preponderance of terminal growth may be detected by comparing the topologies in an observed dendritic network with those of a series of hypothetical growth models. This paper provides the frequency table for models grown by monochotomous, dichotomous and trichotomous branching on random pendant vertices and random arcs for large networks in which 'set theory' contingencies are included. The paper also describes a method of calculating branching probabilities from the measurement of segment lengths, which is a means of testing the last mentioned prediction of the synaptogenic theory of denddritic growth. The method of network analysis is then discussed in relation to probable dendritic growth patterns, the constancy of segment lengths and the interaction of extrinsic and intrinsic factors in determining branching probabilities.


The effects of reduced climbing and parallel fibre input on Purkinje cell dendritic growth. The effects of afferent fibre depletion on the development of the dendritic trees of Purkinje cells in the cerbellum were investigated. Parallel fibres were reduced by postnatal administration of a schedule of low level X-irradiation. Climbing fibers were prevented from innervating the cerebellum by lesioning the olivo-cerebellar tract. Network analysis was performed on Purkinje cells in Golgi-Cox preparations of the vermis of 30-day-old animals. tin the irradiated cerebella Purkinje cells with a 'weeping willow' type morphology predominated. Purkinje cells devoid of their climbing fibre contact exhibited large spines on their main dendritic trunks. In both experimental situations the size of the dendritic tree was reduced. This diminution was the result of a decrease in the total number of dendritic segemnts. Individual segment lengths were largely unalteral. Topological type analysis revealed that the trees had arisen in a manner indistinguishable from terminal dichotomous branching and that the 'weep-willow' pattern was produced by a deviation of branching from a purely random form. The interaction of intrinsic and extrinsic factors in the formation of segments and on the nature of branching were discussed.


Effects of one-stage or serial transections of the lateral olfactory tracts on behavior and plasma testosterone levels in male hamsters. Bilateral transections of the later olfactory (LOT) in male hamsters at the rostral border of the olfactory tubercle or anterior to the tubercle produced severe deficits in mounting, scent marking, food hoarding and nesting behaviors. There were no impairments of these behaviors following unilateral transections. Cutting of the LOT in two stages, and provision of additional experience in sexual and territorial behaviors during the interval between the first and second transection, did not alleviate the behavioral deficits. Impairments in mounting and scent marking were dissociated in some subjects, indicating individual differences in the hamsters' dependence on chemosensory cues for the regulation of these two types of social behavior. It is suggested that the apparent sparing of behavioral function which has been associated with gradual destruction of nervous tissue is due to the development of alternate mechanisms of response to environmental cues, and may be more difficult when brain damage is in structures which initially process these cues. Although sexual and territorial behaviors in the hamster are dependent on gonadal hormones, the observed impairments of these behaviors could not be explained as indirect consequences of lesion effects on the hypophysiogonadal axis. Circulating testosterone (T) levels in experimental subjects were not different from levels in control (sham-operated) subjects. An inverse correlation was observed between the control subjects' circulating T levels and their incidence of scent marking. A similar correlation was observed between postoperative T levels and preoperative marking rates in experimental subjects, despite the fact that most subjects failed to scent mark after bilateral LOT transections. The latter observation strengthens the inference that the bilateral deficits were independent of changes in basal hormone levels.


A primitive gigantopyramidal field buried in the depth of the cingulate sulcus of the human brain. By stereomicroscopical examination of a complete series of pigment preparations up to 1000 mum thick, a gigantopyramidal area in the brain of man is described, which lies in front of the primary motor field on the medial surface of the hemisphere and is almost totally buried in the depth of the cingulate sulcus extending in both length and width over about 15 mm. Serial sections cut in the transverse plane display the field approximately within the limits of the commissura anterior on the one hand and the corpora mamillaria on the other, where it occupies large parts of the dorsal wall of the gyrus cinguli (lower bank of sulcus cinguli) and a small area of the adjacent superior frontal gyrus. The sharply outlined field does not fuse with the primary motor area and is evidently more primitively organized than the precentral motor field. Structural details betray an intimate relationship between this gigantopyramidal field and the archipallial proisocortex. We could clearly trace a gradation, that is, a stepwise change of architectonic features in constant orientation from the limbic proisocortex over a small paralimbic transition zone to the gigantopyramidal field, accounting for the numerous limbic traits recognizable within it, such as, for instance, an accentuated external granular layer, a dense and broad lamina pyramidalis, and a band-like appearance of Va.


Retinofugal pathways in normal and albino axolotls. The retinofugal pathways of normal and albino axolotls have been studied by tracing the transport of radioactive materials after tritiated proline was injected into one eye. The pathways demonstrated by this method include crossed projections to the diencephalon, pretectum, and tectum, and a small component that goes to the midbrain tegmentum in the basal optic root. Ipsilaterally, radioactive label was found in all of the same cerebral regions, but in much smaller quantities. Although on the basis of earlier fiber degeneration studies most of the label could be interpreted as evidence for direct retinofugal pathways, some of the label, especially that in the ipsilateral tectum, does not correspond to a known pathway and may represent a small new component or have been produced by transneuronal transport mechanisms. The pattern of labeling was the same in the albino as in the normally pigmented axolotls. Thus, it appears that the abnormality of the chiasmatic pathway, which has been found in albinos of many different mammalian species, does not occur in axolotls.


Influence of hippocampectomy on gastric ulcer in rats. Hippocampectomized male rats were prepared, and the incidence as well as severity of gastric ulceration upon restraint were compared with those of normal control animals and controls with localized damage to the cortex over the hippocampus. In another experiment, observations on gastric ulceration were made without restraint in hippocampectomized animals, normal controls, controls with cortical damage, vagotomized animals and animals that received hippocampectomy as well as vagotomy. Both in restrained and unrestrained states, the incidence of animals with ulcer as well as the number and the total area of ulcers per stomach were significantly larger in the hippocampal animals than they were in the other animal groups. Vagotomy abolished the effect of hippocampectomy upon gastric ulceration in the unrestrained state. We infer that the hippocampus helps to protect the stomach from ulceration partly by controlling vagal activity.


Central generation of locomotion in the spinal dogfish. After a transection of the spinal cord a dogfish performs continuous swimming movements with a phase lag between adjacent segments. It is shown that the intersegmental coordination remains after an extensive dorsal root transection as well as after curarization. In the former case the motor activity was recorded electromyographically in several segments along the body, in the latter case the intersegmental coordination was evaluated by recording the efferent activity in different ventral roots along the body. It was concluded that a spinal central network can account for the phase lag observed between successive segments during swimming. It was also shown that the efferent activity from parts of the spinal cord with no dorsal roots intact could be influenced by peripheral stimuli such as pressure on the pelvic fins; this result suggests that some afferent fibres reach the spinal cord via the ventral roots.


Glial cells and extracellular potassium: their relationship in mammalian cortex. Simultaneous recordings were made of glial cell potentials and the extracellular potassium concentration ([K+]O) in cat cortex in an attempt to provide more quantitative information about the sensitivity of mammalian neuroglia to changes in [K+]O. A penicillin epileptogenic focus served to generate both transient and sustained elevations in [K+]O, thus allowing measurement of glial membrane potential (Vm) at both resting and increased [K+]O levels many times during the same experiment. Resting Vm averaged--92.6 +/- 10.9 mV for 33 glial cells. With each surface interictal spike, glial cells exhibited slow depolarizations averaging 18.4 +/- 6.5 mV which mirrored rises in [K+]O in many respects. Several discrepancies were found, however, between transient and focal rises in [K+]O and the associated glial cell depolarizations which made it difficult to determine accurately the effect of changes in [K+]O on glial Vm. For example, the amplitude of the glial depolarization caused by a single interictal discharge showed no constant relationship to depth below the cortical surface in contrast to the consistent laminar profile recorded by the K+ electrode. Thus, large glial membrane depolarizations could be recorded at times when there was little or no increase in measured [K+]O. Agreement between changes in [K+]O and glial cell depolarizations was closer to that predicted by the Nernst equation during sustained elevations in [K+]O such as occurred during ictal episodes ('seizures'). These findings may be related in part to methodology as a consequence of the different spatial relationships which exist between glial membrane, K+-electrode tip and released K+. In addition, though, they may indicate the presence of a functional glial syncytium.


Subcellular distribution of LDH isoenzymes in neuronal- and glial-enriched fractions. The LDH isoenzymes of cell organelles (nuclei, mitochondria, microsomes, cytosol) obtained from neuronal- and glial-enriched fractions were determined by disc polyacrylamide electrophoresis and stained for enzyme activity. The quantitative estimation was made either by elution of isoenzymes or by densitometric measurements. The neuronal fraction was found to contain mainly H forms of LDH. The glial fraction also contained H forms but its M/H ratio was higher than that of the neuronal fraction. The cell organelles displayed some specificities with respect to the LDH isoenzymes distribution. The nuclei contained mainly M forms, the mitochondria H forms and the glial microsomal fraction M forms. It is suggested that the different LDH isoenzymes are related to the specific function of the different cell organelles.


The uptake of delta9-tetrahydrocannabinol in choroid plexus and brain cortex in vitro and in vivo. [3H]delta9 Tetrahydrocannabinol (delta9-THC) was actively transported by the choroid plexus and cerebral cortical slices of the rabbit when incubated as a BSA-microsuspension in artificial rabbit CSF. The transport system for delta9-THC in choroid plexus had a V max of 174 nmoles/mg tissue/h, approximately 9-fold greater than that observed for cortical slices. In vivo experiments demonstrated a preferential distribution of delta9-THC in choroid plexus at 1 h after intravenous injection. These results indicate that delta9-THC is actively accumulated by choroidal epithelium and may also be transported across the epithelial stroma into the capillary circulation. This suggests that the choroid plexus participates in the regulation of delta9-THC concentration in CSF and indirectly in brain by means of the "sink" function of the CSF.


Norepinephrine levels in traumatized spinal cord of catecholamine-depleted cats. This study was designed to elucidate the origin of norepinephrine (NE) measured in spinal cord following trauma. In normal cats the NE concentration at the lesion site increased 63% over control 1 h following experimentally produced blunt trauma (400 g-cm). Spinal cords of adrenalectomized cats were also traumatized, but there was no increase in NE levels 1 h post-trauma. Spinal cord NE levels in these animals were not significantly different from normal or adrenalectomized non-injured controls. In the absence of one of the major peripheral sources of catecholamine, the adrenal medulla, our decreased NE levels prompt us to disagree with the hypothesis that NE measured in injured spinal cord is liberated from intrinsic neuronal systems. It is likely that the mechanism of NE accumulation is directly related to increased circulating levels of NE. The authors speculate on a possible reason for the conflicting results obtained by different laboratories in this area of research.


Possible relation between structure and spike shapes of neurones in guinea pig cochlear ganglion. A two-component positive single unit spike could be recorded extracellularly from neurones in the acoustic ganglion of the guinea pig cochlea. Light and electron microscopy showed that the bipolar afferent neurones and their processes were myelinated except at nodes of Ranvier on either side of the cell soma, about 40 mum from the point of emergence of the myelinated processes. This anatomical finding and the properties of the two-component spike suggest that impulse conduction in these cells is achieved by rapid successive activation of the low threshold nodes on either side of the cell soma. The possible advantages of such a conduction system are discussed.


The effect of activation history on tension production by individual muscle units. Isometric responses of individual gastrocnemius muscle units of both fast (F) and slow (S) twitch type were studied during repetitive intracellular stimulation of the innervating motoneurons in anesthetized cats. Paired stimuli usually produced maximum responses (measured in terms of tension-time area) with interpulse intervals between 5 and 10 msec. However, longer pulse trains produced maximum tension-time area per pulse with relatively long interpulse intervals (referred to as the optimum interval). For each unit, stimulus intervals around the optimum produced maximum modulation of tension during unfused tetani. Post-activation potentiation produced shifts in the optimum toward longer intervals. The optimum intervals for type F units were shorter (mean 49.4 msec) than those for type S units (mean 86.9 msec), but there was no difference between the groups when the mean intervals were expressed in ratio with the twitch contraction time, Tc (F units: 1.42 X Tc; S units: 1.31 X Tc). The range of optimum intervals for all gastrocnemius muscle units corresponded to motoneuron firing frequencies of 7-40 pulses/sec, well within the frequency ranges observed for gastrocnemius motoneurons firing under natural synaptic drive. Insertion of a single short interval (5--10 msec) at the onset of a relatively low frequency stimulus train produced a prolonged 'catch-like' enhancement of tension output, particularly in type S units. The duration of the catch-like effect depended on the interval between pulses in the underlying basic train, and was maximum for intervals between 1 and 2 X Tc. The catch-like effect was also seen in type F units but its duration was curtailed by another process called the 'sag' property. The 'sag' property occurred in type F units over a wide range of stimulus intervals (usually 0.5-3 X Tc) but was present in type S units only with relatively long intervals (greater than 2 X Tc). The 'sag' property appears to represent a disenhancement process intrinsic to muscle unit fibers activated in unfused tetani.


Specific angiotensin II receptive neurons in the cat subfornical organ. To test if neurons in the subfornical organ (SFO) are specifically sensitive to angiotensin II (AII) we have applied the AII analog sar1-ala8-AII (P113) directly on to cells in the SFO by microiontophoresis. Adult cats were anesthetized and the SFO exposed for penetration by a 5-barreled micropipette electrode. Of 22 units which responded positively to AII, 7 were also positive to acetylcholine. P113 alone produced either no effect or a decrease in unit firing. P113 plus AII produced antagonism in 17 of 18 units. P113 plus acetylcholine produced antagonistic effects in 5 of 14 cases. Only two units were completely antagonized and 5 units showed agonistic interaction. The most sensitive antagonism with respect to dose of P113 was on neurons responsive only to AII and not to both AII and acetylcholine. We conclude that there are specific AII neurons in the SFO.


Evidence for sar1-ala8-angiotensin crossing the blood cerebrospinal fluid barrier to antagonize central effects of angiotensin II. Injections of angiotensin II into the cerebral ventricles of the rat produces both a drinking and a pressor response. We have measured both responses simultaneously in conscious animals. The effect of saralasin acetate (P113), a specific angiotensin II competitive antagonist, has been studied on these angiotensin II induced responses. The results show that: (1) P113 given intravenously (i.v.) in doses of 500 ng/min or 1800 ng/min has no observable effect on 50 ng angiotensin given intraventricularly (IVT). At 72 mug/min, however, there was a 55% reduction in the drinking and pressor responses to 50 ng angiotensin II (IVT); (2) 500 ng of P113 given IVT abolished the effects of 50 ng angiotensin II also given IVT and (3) P113 given i.v. at all doses antagonized the pressor effects of angiotensin II (i.v.) responses. The data indicate that both the drinking and pressor responses to angiotensin II (IVT) injections are centrally mediated and show that when a high enough dose of P113 is given peripherally the central effects of angiotensin II can be reduced. This suggests that a fraction of the P113 injected i.v. may pass across the blood-CSF barrier. Since P113 has a similar structure to angiotensin II the results have implications for studies in which high peripheral doses of angiotensin II are used.


Effects of glutamate and sulphur containing amino acids on ammonia toxicity and methionine sulphoximine convulsions in mice. Arginine and large doses of glutamate (greater than 500 mg/kg) were found to reduce ammonia toxicity transiently in mice. Smaller doses of glutamate (greater than or equal to 200 mg/kg) were effective when administered with glucose. Cysteic acid, homocysteine and methionine, but not taurine reduced ammonia toxicity. All 4 amino acids reduced the number of convulsions induced by methionine sulphoximine. It is proposed that taurine has a general anticonvulsant action and that cysteic acid, homocysteine and methionine may have a specific effect on the action of ammonia on the central nervous system.


Cerebellar corticonuclear projection in the cat. The vermis of the anterior and posterior lobes. The projection of the vermis of the anterior and posterior lobes of the cerebellum to the fastigial nucleus was studied. It was attempted to obtain lesions restricted to the lobules and this was achieved for the posterior lobe only. The extent of lesions and of additional encroachments were determined by mapping degenerated descending cortical fibers in serial sections. Evidence was obtained that the projection of the vermis is restricted to the fastigial nucleus, without a contribution to the interposed nuclei, in the posterior lobe. Indirect evidence supports the existence of a similar arrangement in the anterior lobe. The projection appears to be distributed ipsilaterally. There is a topographical distribution of the cortical lobules in the different regions of the fastigial nucleus: each lobule projects to the nearest region of the nucleus. There is a divergence of the terminal ramifications of the axons originating from a given lobule within their area of termination. There is also an overlap between the borders of adjacent termination sites. It is concluded that there is a sequential representation of the cerebellar cortex in the fastigial nucleus.


On glutaminase activity in mammalian synaptosomes. A large proportion (30%) of tissue glutaminase activity was found localized in synaptosome fractions as well as purified mitochondrial fractions, where it is also enriched on a protein basis (2-fold). Sulphate was more effective (2-8-fold) than phosphate or chloride in activating the enzyme at concentrations above 10-12 mM, but equivalent to phosphate at lower concentrations (1-3 mM). At CSF levels (0.5 mM), glutamine is readily used by synaptosomes as a substrate in the presence of 10 mM glucose. It constitutes at least 50% to the carbon of aspartate, glutamate and GABA. Pool sizes of these amino acids are maintained in the presence of glutamine and glucose at CSF levels, but not by glucose alone. Ammonium ion at 1 mM substantially (30%) inhibits glutaminase utilisation by synaptosomes. It is suggested that CSF glutamine is a major substrate for the nerve ending in situ.


Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat. An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states.


Rotation induced increases of glucose uptake in rat vestibular nuclei and vestibulocerebellum. A new technique for the autoradiographic measurement of regional cerebral glucose consumption using tracer amounts of radioactive 2-deoxyglucose (2-DG) was employed to study the effects of vestibular inputs on local cerebral glucose metabolism. Rats rotated in the vertical plane showed localized increases of glucose utilization in the vestibular nuclei and several areas of the cerebellum: flocculus, nodulus, ventral uvula, and accessory paraflocculus. The changes in the cerebellum occurred both in the neuronal perikarya-rich granular layer and the neuropil-rich molecular layer. Differential changes resulting from rotation occurred within the granular layer of the nodulus, where at least 7 separate longitudinal zones of differing glucose consumption were seen. This type of longitudinal organization has been described previously in other areas of the vermis with other techniques.


Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat. The distribution of the dentate gyrus associational system was analyzed in naive adult rats and in those with either unilateral or bilateral lesions of the entorhinal cortex. Horseradish peroxidase histochemistry was used to trace the origin and course of this intrinsic fiber system. The fibers originated in the CA3-4 pyramidal cell field, apparently medial to the origin of the Schaffer collateral system, and followed a trajectory which was essentially identical to that described for this system by Zimmer36. The associational terminal field occupied the inner 26% of the dentate gyrus molecular layer in normal rats and 35-38% of the normal width of that layer following either ipsilateral or bilateral entorhinal lesion. These measurements are quite similar to those previously obtained on the commissural system terminal field in the normal and partially deafferented dentate gyrus. These results are interpreted to reflect axon sprouting by the associational fibers into the adjacent deafferented dendritic field.


Evidence for the local synthesis of a transmitter enzyme (glutamic acid decarboxylase) in crayfish peripheral nerve. The activities of three enzymes of neurotransmitter metabolism (choline acetyl-transferase, CAT; acetylcholinesterase, AChE; and glutamic acid decarboxylase, GAD) were studied in normal, transected, and organ cultured crayfish nerves. CAT (to a lesses extent AChE) was dramatically decreased in activity when the nerve was cut proximal to the nerve cell bodies. GAD activity was unaffected by such procedures. In organ cultured nerve, where both motor and sensory axons degenerated, the CAT and AChE activities were virtually absent, whereas GAD activity remained close to normal levels. Inhibition of protein synthesis in cultured nerve caused the GAD activity to decrease rapidly. In view of these data, and the well documented fact that motor axons survive axotomy whereas sensory axons do not, a hypothesis that GAD is synthesized in the peripheral nerve is presented.


The protein requirement of laying pullets with changing seasons in the tropics. 1. The protein requirements of White Leghorn laying pullets were evaluated in summer and winter using isocaloric diets containing 12-8, 15-0, 16-6, 18-5 and 21-6% protein. 2. The age at 50% production of summer-raised pullets was about 2 weeks later than that of winter-raised pullets irrespective of the concentration of dietary protein. 3. Egg production in summer-increased with increasing concentrations of protein up to 18-5%; further increases had no significant effect: in winter, egg production was similar provided the diet contained at least 15-0%. 4. The data on egg production, food consumption and egg weight indicated that the protein requirement of White Leghorn pullets is met by diets containing about 19% protein in summer and 15% in winter.


Chick embryo heart rate during the last week of incubation: population studies. 1. A technique has been developed for the study of embryonic heart rate during the last week of incubation in a population of 84 embryos. 2. Heart rate is characteristic for a particular embryo but there are clear differences between individuals. 3. The population mean heart rate decreased from 262 beats/min at 14 d to a minimum of 250 beats/min at 19-5 d and then increased rapidly to more than 270 beats/min before hatching. 4. This pattern was repeatable and independent of the flock age. 5. Embryonic heart rate was also independent of egg size and hatching time. 6. The heart rate of male embryos was one to two beats/min lower than that of females.


Effects of different rates of inbreeding on the body weight and rate of gain of Japanese quail. 1. The effect of regular full-sib and double first cousin mating on body weight and rate of gain over six generations of Japanese quail was determined. 2. The depression of characters was more pronounced in the full-sib than in the double first cousin mating system, the relative depression due to parental inbreeding and offspring inbreeding depending on the magnitude of parental effect and individual's own genotypic effect on the character. 3. The body weight and rate of gain taken at an early age showed greater depression due to parental inbreeding whereas that taken near sexual maturity was depressed mainly due to individual's own inbreeding.


Purification of p-hydroxyphenylpyruvate hydroxylase from rat liver--requirement for cofactors. The enzyme p-hydroxyphenylpyruvate hydroxylase (EC 1.13.11.27) from rat liver was studied with the assay method which measures the release of 14CO2 from p-hydroxyphenyl [carboxy-14C]pyruvate. Extensive dialysis of the crude enzyme extract against Tris buffer or purification involving ammonium sulfate, gel filtration, and ion exchange results in loss of enzyme activity that can be reactivated by Fe2+, dichlorophenolindophenol, and various other agents. The effect of these activators depends critically on their final concentration in the assay media. A 70-fold purification of the enzyme fraction yielded a preparation which behaved as a single protein band in Sephadex G-150. It had an isoelectric point at 5.85 and molecular weight of 63 000. The enzyme obtained appears to be different in some respects from those described by other workers from the liver of dog, human, chicken, and frog.


Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity. A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.


Purification and properties of a carboxylesterase from the liver of tiger shark (Galeocerdo cuvier). A procedure is described for the purification of a carboxylesterase from shark liver, using a chloroform-acetone powder prepared from the liver as the starting material. The yield of purified enzyme is approximately 50 mg from 530 g of chloroform-acetone powder. The preparation is electrophoretically homogeneous. Active-site titrations with paraoxon gave an equivalent weight of approximately 83 000. The molecular weight, found from sedimentation equilibrium experiments, is approximately 80 000. There is no evidence of any association or dissociation of this species. The enzyme shows a marked preference for aryl esters over alkyl esters, in contrast to other carboxylesterases so far studied. The amino acid composition of the purified enzyme is reported.