Renal consequences of irradiation of the spleen in lymphoma patients.

The authors have studied the consequences of irradiation of the upper part of the left kidney during treatment of the spleen. Seventy-four patients with lymphoma were entered in the study. They have all been followed up for between three and five years. Renal function was assessed by physical examination, biological tests, intravenous pyelograms and nephrotomographies, isotope scans with 197Hg neohydrin, dynamic studies with 131I hippuran and 99Tcm DTPA. No significant changes have been noted for blood pressure, biological tests or IVP. Eighteen months after irradiation renal tomograms showed cortical atrophy of the superior pole of the left kidney. 197Hg neohydrin started to show reduced uptake of the isotope in the irradiated region of the left kidney by the eighth month. 131I hippuran and 99Tcm DTPA detected abnormalities respectively five and three months after irradiation. No compensatory hypertrophy nor change in the overall kidney function have been noted. In Hodgkin's disease, radiotherapy has proved its efficiency in splenic involvement and the lack of secondary renal side effects. On the other hand, morbidity was shown to occur in 5% of cases after splenectomy. From these data, it is proposed to prefer radiotherapy rather than surgery for splenic treatment.


The recovery of iron uptake in erythropoietic bone marrow following large field radiotherapy.

Large X-ray fields, such as those used to irradiate major lymph-node areas in the treatment of lymphomas, often irradiate large areas of haemopoietic bone marrow. The absorbed doses received by the marrow are close to the tolerance level. Quantitative scanning of the bone marrow, using 52Fe and a digital whole-body scanner, has been carried out in a series of 22 patients treated by radiotherapy up to nine years previously in order to assess the extent and recovery of their erythropoietic marrow. The results showed large variations from patient to patient; in some patients the iron uptake in the marrow returned to near normal levels in two to three years, while in others the uptake remained suppressed after seven to eight years. The tolerance dose for the bone marrow appeared to be about 1100 ret. There was some evidence of a more rapid recovery of erythropoietic function in males than females, but no evidence to show that age of patient, type of disease or whether chemotherapy had been used influenced the results. Patients who showed a decreased iron uptake in an irradiated region of marrow generally showed a compensating increased uptake in unirradiated regions, which in some cases was associated with anaemia.


Osteochondral fractures of the dome of the talus.

Osteochondral fracture of the talar dome is an uncommon lesion occurring after ankle inversion and tearing of the lateral ligaments. This lesion can be overlooked if internal oblique radiographs are not obtained. The value of tomography is discussed. Symptoms may persist for many months if accurate radiographic diagnosis is delayed. Prompt arthrotomy is indicated to prevent post-traumatic arthritis of the ankle joint.


Lymphography in angio-immunoblastic lymphadenopathy.

Angio-immunoblastic lymphadenopathy (AIL) produces a characteristic lymphoproliferative syndrome, with characteristic lymphographic appearances. The authors studied the lymphographic manifestations of 18 cases of AIL. In 15 out of 18 cases, enlargement is observed in all the lymph nodes with a lacy or reticular storage pattern and sharp, well delimited margins. This lymphographic appearance reflects the histologic changes; only the peripheral sinuses, which are not involved, can be observed on lymphography.


Clinical evaluation of computer processing of liver gamma camera scans.

A prospective study to assess the clinical usefulness of computer processing of liver scans has been carried out on 203 patients. All patients have had six months follow up to confirm the diagnostic accuracy of the scan results. Four presentations have been studied using ROC analysis: (i) original gamma-camera pictures; (ii) processed images obtained using a non-stationary filter; (iii) images processed using nine-point smoothing; (iv) images obtained by linear interpolation at 25 isocount levels of display. It is concluded that pictures obtained by use of a non-stationary filter at 25 isocount levels are superior to a conventional gamma-camera pictures and displays obtained by linear interpolation only. All three are considerably superior to the images obtained by nine-point smoothing in detection of focal space-occupying lesions. Based on the results obtained, a strategy for the rational use of computer processing of gamma-camera liver scans is proposed.


Lymphoscintigraphy: a comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate.

In vitro comparison of 99Tc(m) antimony sulphide colloid and 99Tc(m) stannous phytate as well as in vivo studies in six rabbits and seven patients indicate disparity in the colloidal properties and localization of these two agents. The variability in lymphatic uptake and the relatively poor quality of scintigraphic images following interstitial injection of 99Tc(m) stannous phytate, when compared with 99Tc(m) antimony sulphide colloid, provide evidence of the unsuitability of this agent for lymphoscintigraphy. Maintenance of the diagnostic quality of the lymphoscintigraphic image and adherence to interpretive criteria already established therefore preclude the routine use of 99Tc(m) stannous phytate for interstitial lymphoscintigraphy.


High thyroid radiation dose associated with 131-I-19-iodocholesterol adrenal scanning.

We have examined two patients undergoing 131I-19-iodocholesterol adrenal scans in order to assess thyroidal radiation dose. Thyroid uptakes of 3--5% of the administered 2 mCi dose were found despite prior administration of Lugol's iodine. Analysis of serum samples over a ten day period after iodocholesterol injection indicated that less than 10% of the radioactivity was free iodide. Kinetic results showed a high value for the thyroid/plasma 131I ratio indicating thyroid retention of 131I. This was substantiated by thyroid scintigrams. The thyroid radiation dose was estimated to be 200--250 rad for the two patients. The associated carcinogenic risk is of sufficient magnitude, in our opinion, to warrant regular follow-up of all patients who have undergone 131I-19-iodocholesterol adrenal scanning.


A single injection technique for subtraction of blood background in 131I-hippuran renograms.

A method of subtracting blood background during proberenography is presented which does not require a prior injection of RIHSA and which produces results approximately 11% higher than the RIHSA method. The new method treats the renogram up to two-and-a-half minutes as a combination of a fraction of the blood curve and a fraction of the integral of the blood curve. Analysis of the data, using either a computer or a programmed calculator, enables these two fractions to be calculated, hence producing the "background subtraction factor" and the "uptake constant".


Blood flow clearance changes in pig skin after single doses of X rays.

Early and late changes in the functional vascularity of pig skin have been evaluated after X-irradiation. These changes were assessed using a quantitative isotopic clearance technique. Two waves of radiation-induced changes in isotopic clearance were demonstrated. The first wave, observed after an interval of three weeks, was characterized by the faster clearance of the tracer from areas of irradiated skin. The second wave, which reached a peak after 12 weeks, was denoted by a slowing of the clearance rate relative to normal skin. The modification in vascular function observed at 12 weeks was transient, function returning to normal as late radiation damage developed. The changes observed in the pig have many similarities with those recorded in man but are markedly different from those found in rodents. These differences are discussed with respect to the vascular structure of the skin of the animal species investigated.


Changing pattern in aetiology of pancreatitis in an urban Swedish area.

Two groups of patients admitted with a first attack of acute pancreatitis are reviewed. The first group, consisting of 105 patients, was admitted between 1968 and 1969; the second group of 204 patients was admitted between 1974 and 1975. These groups were compared with one of 454 patients admitted between 1956 and 1960 whose details were published earlier by our unit (Edlund et al., 1968). The aim of this study was to determine whether the incidence of factors associated with pancreatitis within the population of the city of Göteborg had changed in the 20-year period. In the 1956--60 group gallstone disease was the main associated factor (68 per cent), but in the later groups alcohol-induced pancreatitis assumed the leading role (68 and 66 per cent respectively). Alcohol-induced pancreatitis tended to occur at a younger age than gallstone pancreatitis. Thirty-one per cent of 449 patients admitted with an acute attack of alcoholic pancreatitis in the two last periods of study had had previous attacks.


The role of grey scale ultrasonography in the investigation of jaundice.

Sixty-seven patients were prospectively studied using grey scale ultrasound (GSU) to assess its possible role as part of a jaundice investigation programme. All scans were performed by one radiologist, without clinical information. When intrahepatic ductal dilatation was found an attempt was made to establish the level and cause of obstruction. The calibre of the intrahepatic bile ducts was correctly reported in 66 patients (98 per cent). Forty-three proved to have extrahepatic cholestasis, 24 had intrahepatic cholestasis. No patient with intrahepatic cholestasis had dilated ducts seen on ultrasound. In 43 patients with obstructive jaundice, GSU accurately detected the level of obstruction in 28. This accuracy varied with the cause of obstruction. A direct indication of diagnosis was possible in 45 of the 67 patients. In a unit specializing in the management of complicated hepatobiliary problems, GSU has been shown to be accurate in differentiating extra- from intrahepatic jaundice. Being non-invasive, it appears ideally suited for use as a screening procedure, permitting selection of appropriate invasive investigations to provide complete preoperative imaging of the biliary tree. In patients with jaundice due to gallstones, GSU may be the only imaging technique required before surgery provided good operative cholangiography is available.


The ultrasonic demonstration of portacaval shunts.

This study explores the use of ultrasound in the management of patients with portacaval anastomosis. Ten patients were studied; in 8 of these the status of the anastomosis was well demonstrated. It is suggested that ultrasound should be the initial investigation to determine the patency of a shunt.


Grey-scale ultrasonography and endoscopic pancreatography after pancreatic trauma.

We have recently used grey-scale ultrasonography and endoscopic pancreatography to investigate 11 patients with symptoms attributed to pancreatic trauma weeks, months or even years earlier. The pancreas was normal in one patient, and another, who presented with pain and jaundice after a car accident, was shown to have cancer of the pancreatic head. The remaining patients all had local lesions due to trauma; ultrasound showed a mass or cyst close to the point of duct obstruction or stenosis shown on pancreatography. Ultrasonography and pancreatography can together provide a precise map with which to plan effective management in patients having suffered pancreatic trauma.


Infusion cholecystography in the diagnosis of acute cholecystitis.

The use of infusion cholecystography as an aid in the diagnosis of acute cholecystitis was investigated in 21 patients. Seventeen of 18 patients (94 per cent) with positive cholecyst-tomograms who underwent laparotomy had confirmation of acutely inflamed gallbladders both macroscopically and histologically. These findings suggest that infusion cholecystography can make a significant contribution in reducing the incidence of misdiagnosis in acute cholecystitis, and that the investigation should be part of the management of patients in whom early surgery is planned.


Operative choledochoscopy.

We have reported the results of 121 examinations with the rigid choledochoscope performed by 13 different surgeons between 1969 and 1977. Pre-exploratory choledochoscopy was performed in 48 patients with a diagnostic accuracy of 94 per cent. Post-exploratory choledochoscopy was used in 73 patients to define whether the common bile duct had been adequately cleared of stones. Fifty-one patients were correctly assessed as having a clear duct and unsuspected residual calculi were demonstrated by choledochoscopy in 13 patients. However, choledochoscopy failed to identify 9 patients with retained stones. The accuracy of post-exploratory choledochoscopy alone was 87 per cent and the accuracy of post-exploratory cholangiography was 82 per cent, but when choledochoscopy was combined with post-exploratory cholangiography there were no errors. We conclude that the addition of choledochoscopy to conventional radiological techniques is likely to reduce the incidence of residual calculi after choledochotomy.


Modified surgical procedures in intestinal tuberculosis.

The results of modified surgical procedures in intestinal tuberculosis in 79 patients are presented. Special emphasis is laid on the role of limited ileocaecal resection and ileoplasty. These procedures are safe, quick and easy with preservation of functional portions of the bowel. They are of immense value in emergencies in chronically ill and emaciated patients.


The fibrinolytic activity of varicose veins.

The plasma fibrinogen concentration, plasma fibrinolytic activity and the vein wall fibrinolytic activity of hand, groin, knee, ankle and perforating veins have been studied in 10 patients with skin changes in the lower leg secondary to venous disease (lipodermatosclerosis), in 10 patients with uncomplicated varicose veins and in 17 normal volunteers undergoing surgery. There was significantly more vein wall fibrinolytic activity in normal volunteers than in the patients with lipodermatosclerosis, not only in the ankle (P less than 0.001) but also in the hand (P less than 0.05). It is suggested that the reduced tissue fibrinolytic activity is a causative factor in the skin changes and ulceration of the post-phlebitic leg, and that since the reduced activity is not confined to the leg, it may be a primary systemic defect rather than a state secondary to venous congestion.


Prevention of intraperitoneal adhesions: a comparison of noxythiolin and a new povidone-iodine/PVP solution.

Peritoneal adhesions were induced in 250 female Wistar rats by the excision and closure of a right lower quadrant parietal peritoneal defect. After closure of the defect each rat was randomly allocated to one of five treatment groups: A, control with no instillate; B, control with Ringer solution; C, noxythiolin 0.5 per cent solution; D, noxythiolin 1 per cent solution; E povidone-iodine/PVP solution. Two millilitres of the appropriate solution were injected into the peritoneal cavity just before closure of a standard 4-cm midline incision. Assessment of adhesion formation was made at 1 week in ignorance of the treatment group. Noxythiolin 1 per cent was more effective than Ringer solution and noxythiolin 0.5 per cent in reducing the mean number of adhesions (P less than 0.05) but was inferior to povidone-iodine/PVP (P less than 0.05). Povidone-iodine/PVP solution significantly reduced the number of adhesions compared with the four other groups. In addition, it significantly reduced the mean length of attachment of each adhesion compared with the two control groups (P less than 0.001).


Mercury nephrotoxicity from peritoneal lavage.

Two cases of acute renal failure following intraperitoneal administration of mercury are described.


A new appliance for collecting ileostomy and jejunostomy fluid in the postoperative period.

A new lightweight two-piece ileostomy appliance was tested in 11 patients with newly established ileostomies and jejunostomies. Seven of the patients presented difficult stoma care problems. The appliance was fitted in theatre on completion of the operation and the patient was followed until discharge from hospital. The appliance remained in place for an average of 4.8 +/- 1.2 days. In a total of 204 patient-days the pouch became dislodged from the flange on 10 occasions and there was leakage under the body flange on 7 occasions. All but one of the patients continued to use the appliance on discharge. No patient was allergic to the appliance nor complained of odour. It is concluded that this new appliance represents an important advance in postoperative stoma care.


Hyperosmolar diabetes presenting as acute urinary retention: report of three cases.

Three elderly patients presented at one hospital in a 2-week period with acute urinary retention precipitated by the hyperosmolar non-ketotic diabetic state. In each case routine urine testing was reported as showing 1 per cent glycosuria. The first two patients were admitted at night and blood glucose estimations were not done. This led to a delay of 16 and 12 h respectively before the appropriate therapy was instituted. It is suggested that this clinical presentation, previously unreported, may not be a rarity and represents an avoidable cause of death in patients with acute urinary retention.


Cytological study of fluid from breast cysts.

A series of 215 patients with breast cysts have provided 348 specimens of cyst fluid for cytological diagnosis. Only one of these specimens was reported positive for malignant cells and this patient had a carcinoma. Nine specimens were reported as suspicious, but none of these patients had or subsequently developed carcinoma. In 338 specimens cytology was negative. A total of 178 patients (294 specimens) was available for follow-up. Of these 2 proved to have carcinomas on immediate follow-up, i.e. a lump presisted after aspiration, and a further 2 patients developed cancers in the same breast, one 4 and the other 7 years after aspiration. We therefore conclude that the routine submission of breast cyst fluid for cytology is wasteful of time and resources.


Haematogenous osteomyelitis of the metatarsal sesamoid.

A case of haematogenous osteomyelitis of the medical first metatarsal sesamoid is presented and the differential diagnosis discussed. Review of the literature suggests that the condition is rarely seen and tends to present in childhood and adolescence. This contrasts with metatarsal sesamoid osteomyelitis due to direct spread of infection, which occurs in the elderly as an important complication of the diabetic foot.


Psychological rehabilitation after myocardial infarction.

The value of psychological counselling in rehabilitating patients after myocardial infarction was assessed. A total of 143 men who had recently had a myocardial infarction were randomly allocated to either a group receiving intensive rehabilitation or a control group, their outcome being examined after six months. Patients with neurotic, introverted personalities had a poor outcome in the control group but a satisfactory outcome when rehabilitated. Neurotic personalities responded to help, and rehabilitative measures did not increase neurosis. In addition all patients with a negative attitude towards their illness and future had a poor outcome but those with a positive attitude did well. Selection by simple methods of patients who would benefit from psychological rehabilitation seems desirable.


Shortening hospital stay for psychiatric care: effect on patients and their families.

A one-year cohort of patients from a defined catchment area with acute functional disorders were allocated at random to brief care (experimental group) or standard care (control group) in hospital to examine the effect of shortening hospital stay on the clinical and social functioning of patients and the distress abnormal functioning caused to others. A total of 127 patients were interviewed on entry to the study, and 106 were followed up. The brief care group had significantly shorter mean and median lengths of stay than the control group, but there was no difference between the groups in the number of days spent in hospital during subsequent admissions. The groups were well matched for clinical and social variables. Rates of improvement over 13 weeks were essentially the same by all measures of outcome, including the Present State Examination and Patient's Behaviour Assessment Scale, which was developed for the study to measure deterioration in behaviour and social functioning and adverse effects and distress on others. There was no difference between the two groups in burden to the community supporting services, social security requirements, or GP attendances. Improvement rates were nearly identical on all measures within and across diagnostic subgroups. Brief care resulted in a 33% reduction in average length of stay compared with the year before but was associated with a corresponding increase in day hospital use. The short-stay policy continued the year after the study finished.The findings confirm the value of shortening hospital stay and improving day care facilities for most localities.


Value of 1-alpha-hydroxy vitamin D3 in treatment of primary hyperparathyroidism before parathyroidectomy.

The postoperative course of six patients with primary hyperparathyroidism and obvious radiological evidence of bone disease pretreated with 1-alpha-hydroxy vitamin D3 (1 alpha HCC) was indistinguishable from that of six patients with a similar clinical and radiological picture who were not pretreated. 1alphaHCC may increase the hypercalcaemia in some cases and cannot be recommended for the routine preparation of such patients for surgery.


Open-access endoscopy service for general practitioners.

An open-access general-practitioner referral service for endoscopy of the upper gastrointestinal tract was established in a district general hospital, and the impact of the service over three years was assessed. The reason for referral, duration of symptoms, and amount of disease detected were the same in patients referred by general practitioners and those attending from hospital outpatient departments. Despite a steady increase in the number of patients referred for endoscopy, the number of barium-meal examinations performed did not correspondingly decrease. The number of ulcers and cancers detected in each six-month period of the study did not increase, and the combined overall pick-up rate for these two conditions fell from 25% to 13%. All general practitioners in the area were sent questionnaires. Most thought that clinic referral had been reduced and patient management helped as a result of the introduction of the service. While the value of negative endoscopic findings cannot be assessed, there is little objective evidence of benefit. Hence the large increase in numbers of endoscopies performed as a result of the introduction of the service cannot be justified.


Population characteristics and the distribution of general medical practitioners.

By applying the logic of the Resource Allocation Working Party to the analysis of the distribution of general medical practitioners, the relevant Family Practitioner Committee (FPC) populations were weighted according to known patterns of use related to specific characteristics--namely, age, sex, marital state, and socioeconomic group. Comparative weightings were also calculated using standardised mortality ratios. Adjusting the populations to take account of differential use has relatively little impact on national variations in list sizes but an appreciable effect on particular FPCs, notably East and West Sussex, Dorset, and the Isle of Wight. Inequalities in the distribution of general practitioners are increased considerably, however, if figures taking account of the inflation of list sizes and cross-boundary flows are used. To formulate and monitor policy about the distribution of general practitioners more sensitive measures of population and its likely demand for services must be developed.


Patterns of bleeding in adolescents with severe haemophilia A.

Eighty-two boys with severe haemophilia A who spent some time at Lord Mayor Treloar College during 1973-7 were studied. All episodes of bleeding that occurred during term time were recorded, along with the number of transfusions. The bleeding frequency among these boys, most of them aged 10-17 years, increased steadily from 8,31 episodes/100 days in 1973 to 12,63 episodes/100 days in 1977. At the same time there was a steady fall in bleeding frequency with age. Altogether 24% of bleeding episodes were into the elbow joint, 22% into the knee, and 15% into the ankle. As the boys grew older the proportion of bleeding episodes in the legs declined and that in the arms increased. The overall results reflect the fact that special schools now see only the severest cases of haemophilia. The pattern of bleeding during adolescence suggests that concepts of management of arm bleeding need modifying.


Smoking and subarachnoid haemorrhage.

A retrospective study of 208 patients with ruptured cerebral aneurysms showed a highly significant excess of cigarette smokers among both men and women compared with the expected incidence. Results suggested that continued smoking increases the risk of suffering a subarachnoid haemorrhage (SAH) by a factor of 3.9 for men and 3.7 for women. Other factors besides smoking must affect the genesis of aneurysmal SAH since it is found in non-smokers, but continued cigarette smoking appears to increase substantially the risk of aneurysmal SAH occurring.


Excess smoking in malignant-phase hypertension.

The smoking habits of 82 patients with malignant-phase hypertension were compared with those of subjects in three control groups matched for age and sex. Sixty-seven (82%) of the patients with malignant-phase hypertension were smokers compared with 41 (50%) and 71 (43%) of the patients in two control groups with non-malignant hypertension, and 43 people (52%) in a general population survey. The excess of smokers in the malignant-phase group was significant for men and women, together and separately, for cigarette smoking alone, and for all forms of smoking. There were no significant differences between the control groups. The chance of a hypertensive patient who smoked having the malignant phase was five times that of a hypertensive patient who did not. Twelve patients in the malignant-phase group had never smoked. All were alive three and a half years on average after presentation (range 11 months to seven years). Twenty-four (36%) of the smokers with malignant-phase hypertension died during the same period. The mortality rate was significantly higher among patients with renal failure, as was the prevalence of smoking. Eighteen patients with malignant-phase hypertension had a serum creatinine concentration higher than 250 mumol/l (2.8 mg/100 ml); 17 were smokers and one an ex-smoker. Eleven of these 18 patients died.It is concluded that hypertensive patients who smoke are much more likely to develop the malignant phase than those who do not, and that once the condition has developed it follows a particularly lethal course in smokers.


Malignant hypertension and cigarette smoking.

The smoking habits of 48 patients with malignant hypertension were compared with those of 92 consecutive patients with non-malignant hypertension. Thirty-three of the patients with malignant and 34 of the patients with non-malignant hypertension were smokers when first diagnosed. This difference was significant, and remained so when only men or black and white patients were considered separately. Results suggest that malignant hypertension is yet another disease related to cigarette smoking.


Study of special-care baby services in North-west Thames region.

During three months in 1975 admissions to 17 of the 21 special-care baby units in the North-west Thames region were analysed by birth weight and category of care. Of the 1,718 babies admitted, one-third needed only observation. Neonatal intensive care formed only a small proportion of the work load in most units. Considerable variation in the pattern of admissions was found. There was some evidence of concentration, about 100 babies being transferred for urgent medical or surgical reasons, and the work load of one unit suggested that it was serving as a referral centre. It is concluded that the quality of care given to some infants needing intensive care might be improved by greater concentration, and that some units should review their admission policies in order to prevent unnecessary postpartum separation of mother and baby.


Medical manpower two years on.

Medical manpower in Britain, with particular reference to the NHS, was analysed for 1976 and 1977. The output of British medical schools increased. The total of doctors in the NHS rose by 2% between 1975 and 1976 and by 2.4% between 1976 and 1977. The highest and lowest growth rates were in junior and senior hospital staff grades respectively, while the highest growth rate in career grades seemed to be in community medicine and health. The inflow of overseas doctors remained high, though few tended to remain permanently in Britain. Continuous evaluation of the medical manpower position is needed before long-term predictions can confidently be made.


Short-term treatment of gonorrhoea with intramuscular and oral forms of trimethoprim-sulphamethoxazole.

Fifty-nine male patients and 41 female patients with uncomplicated gonorrhoea were treated with an intramuscular dose of 1600 mg sulphamethoxazole plus 320 mg trimethoprim followed by an oral dose of 2400 mg sulphamethoxazole plus 480 mg trimethoprim 12 hours later. Forty-nine out of 52 male patients and 37 out of 38 female patients who were re-examined were cured. One of the men probably had a reinfection.


Antibodies to Chlamydia trachomatis in acute salpingitis.

Recent isolation studies have shown Chlamydia trachomatis to be an important aetiological agent in acute salpingitis in women. The present serological study indicates that C. trachomatis is the probable aetiological agent in two-thirds of 143 women with pelvic inflammatory disease (PID). In general, high levels of chlamydial antibody were found in sera and fluids aspirated from the pouch of Douglas and such antibody titres were shown to correlate with the severity of clinically graded tubal inflammation.


Ureaplasma urealyticum and Mycoplasma hominis in chlamydial and non-chlamydial nongonococcal urethritis.

Urethral specimens from 726 patients with nongonococcal urethritis (NGU) were examined for Chlamydia trachomatis, Ureaplasma urealyticum, and Mycoplasma hominis. Chlamydiae were isolated from 35.9% of ureaplasma-positive patients and from 36.5% of ureaplasma-negative patients. Ureaplasmas were isolated from 52.5% of chlamydia-positive patients and from 53.1% of chlamydia-negative patients, an observation which contrasts with that of some workers who have suggested that ureaplasmas are significantly associated with chlamydia-negative NGU. Furthermore, the numbers of ureaplasmas isolated from patients who did or did not harbour chlamydiae were not significantly different nor was there a particular association of ureaplasmas with chlamydia-negative NGU in patients experiencing their first episode of disease. In addition, M. hominis was not isolated more frequently from those from whom chlamydiae were or were not isolated. The only significant associations were the isolation of M. hominis from patients who were ureaplasma-positive and of ureaplasmas from those who were M. hominis-positive. These findings do not necessarily mitigate against ureaplasmas being responsible for some cases of chlamydia-negative NGU.


Necrotising balanitis due to a generalised primary infection with herpes simplex virus type 2.

Virological studies have proved herpes simplex virus type 2 to be the cause of the severe primary infection in a 37-year-old man with necrotising balanitis. Symptoms of urethritis preceded the appearance of a severe local lesion; dissemination of infection occurred and lesions developed on the skin of the scalp, neck, trunk, buttocks, arms, legs, and feet. No evidence of involvement of the central nervous system was found, and the penile and skin lesions improved rapidly after the application of 5% idoxuridine in dimethylsulphoxide. Recurrences occurred at various skin sites at six to seven months after the primary infection.


Serum immunoglobulin response in uncomplicated gonorrhoea.

Sera from 225 men and 140 women were examined by an indirect immunofluorescent antibody technique for antibody reactive with Neisseria gonorrhoeae. Antigonococcal IgM was demonstrated at a titre of greater than or equal to 16 in about 45% of infected, but in only 3% of non-infected, patients. Most of this antibody occurred in sera of patients who had been infected for less than 14 days. Antibody of the IgA class was found at a titre of greater than or equal to 16 in over half the infected, but in none of the non-infected, patients. IgG antibody reactive with the gonococcus was found in each infected patient at a titre of greater than or equal to 16 but in only 8% of controls. The mean log titre of this antibody was significantly higher in patients who had been infected for more than seven days than in those whose infection was of shorter duration.


Current approaches to the diagnosis, treatment, and reporting of trichomoniasis and candidosis.

The current approach to the management of trichomoniasis and candidosis in sexually transmitted disease (STD) clinics in England and Wales is described. Microscopy alone was used in the diagnosis of trichomoniasis in 44% of clinics and of candidosis in 35% of clinics. Oral metronidazole was used for the treatment of trichomoniasis in women in 92% of clinics. Vaginal pessaries containing nystatin or clotrimazole were routinely used to treat candidosis in 95% of clinics. Male sexual contacts of female patients with candidosis and trichomoniasis were invited to attend for examination in 88% of clinics. Physicians in 81% of clinics prescribed treatment on epidemiological grounds for male contacts of female patients with trichomoniasis. A more uniform approach to the diagnostic categories used for the quarterly returns for cases treated epidemiologically is recommended.


A theory of the epidemiology of gonorrhoea.

Gonorrhoea is a typical endemic disease. Its continuity has been traditionally attributed to the existence of a pool of infected promiscuous women. Alternative theories have suggested a dynamic approach which gives equal importance to the man and the woman. Models constructed to simulate the epidemiology of gonorrhoea have so far failed to be realistic. An hypothesis that the distribution of infections is limited by the number of opportunities for transmission presented by the pattern of sexual behaviour may explain the low prevalence of the disease in England.


Treatment failure with penicillin in early syphilis.

A patient with primary syphilis had a recurrence of his penile chancre after generally acceptable penicillin treatment. Retreatment with a similar but extended penicillin regimen was successful. This is the first report of such a treatment failure.


Duchenne muscular dystrophy: plasma membrane loss initiates muscle cell necrosis unless it is repaired.

Study of biopsies from 30 boys with Duchenne muscular dystrophy suggests that necrosis of muscle cells is initiated by loss of plasma membrane, followed, after a short interval, by Z disc lysis and mitochondrial changes to constitute the picture of fully developed necrosis. Empty basal lamina tubes containing collagen indicated that regeneration may fail to occur. The tubes form a basis for collagen deposition. Evidence suggests that small patches of membrane loss can be repaired, though a slice of superficial cytoplasm is lost, and a piece of detached basal lamina results. The markedly hypercontracted fibres seen did not show features of necrosis.


Defective cardiovascular reflexes and supersensitivity to sympathomimetic drugs in autonomic failure.

In 10 patients with chronic autonomic failure the clinical features and cardiovascular reflexes were correlated with the pressor responses to intravenous noradrenaline and tyramine. In all patients there was an exaggerated response to noradrenaline but a normal or only mildly exaggerated response to tyramine. Patients with lack of sinus arrhythmia and by implication baroreceptor reflex loss had greater responsiveness to pressor drugs than patients with preservation of this reflex. The responses to tyramine infusions imply that there must be sufficient noradrenaline released at defective sympathetic endings for a pressor response to occur. However, the lack of rise of plasma noradrenaline following tyramine, except in the patients with pure autonomic failure, clearly separates these responses from those of normal subjects. These results can be explained by the presence of lesions of both central and peripheral sympathetic pathways in patients with chronic autonomic failure and multiple system atrophy or Parkinsonism. The peripheral lesion, which is incomplete, may consist of replication of the receptors so causing supersensitivity with a duration of response that is little prolonged. The peripheral defect in the two patients with pure autonomic failure was found to be more complex and the prolonged response in one of these patients suggests the possibility of defective re-uptake or metabolism of noradrenaline. Clearly further study of the defects of sympathetic endings is required, including the use of other techniques such as catecholamine fluorescence. The extreme supersensitive responses underline the need for blood pressure monitoring during pressor drug studies prior to treatment, if the hazards of recumbent hypertension are to be avoided.


Subjective referral of the timing for a conscious sensory experience: a functional role for the somatosensory specific projection system in man.

Subjective experience of a peripherally-induced sensation is found to appear without the substantial delay found for the experience of a cortically-induced sensation. To explain this finding, in relation to the putative delay of up to about 500 ms for achieving the "neuronal adequacy" required to elicit the peripherally-induced experience, a modified hypothesis is proposed: for a peripheral sensory input, (a) the primary evoked response of sensory cortex to the specific projection (lemniscal) input is associated with a process that can serve as a 'time-marker'; and (b), after delayed neuronal adequacy is achieved, there is a subjective referral of the sensory experience backwards in time so as to coincide with this initial 'time-marker'. A crucial prediction of the hypothesis was experimentally tested in human subjects using suitably implanted electrodes, and the results provide specific support for the proposal. In this, the test stimuli to medial lemniscus (LM) and to surface of somatosensory cortex (C) were arranged so that a minimum train duration of 200 ms or more was required to produce any conscious sensory experience in each case. Each such cerebral stimulus could be temporally coupled with a peripheral one (usually skin, S) that required relatively negligible stimulus duration to produce a sensation. The sensory experiences induced by LM stimuli were found to be subjectively timed as if there were no delay relative to those for S, that is, as if the subjective experience for LM was referred to the onset rather than to the end of the required stimulus duration of 200 ms or more. On the other hand, sensory experiences induced by the C stimuli, which did not excite specific projection afferents, appeared to be subjectively timed with a substantial delay relative to those for S, that is, as if the time of the subjective experience coincided roughly with the end of the minimum duration required by the C stimuli. The newly proposed functional role for the specific projection system in temporal referral would be additional to its known role in spatial referral and discrimination. A temporal discrepancy between corresponding mental and physical events, i.e., between the timing of a subjective sensory experience and the time at which the state of 'neuronal adequacy' for giving rise to this experience is achieved, would introduce a novel experimentally-based feature into the concept of psychophysiological parallelism in the mind-brain relationship.


A spinocerebellar degeneration with X-linked inheritance.

A spinocerebellar degeneration is described affecting ten members of a family over five generations with transmission by X-linked recessive inheritance. The clinical features include pes cavus, scoliosis, increased lumbar lordosis and signs of cerebellar dysfunction. There is a slowly progressive distal muscle atrophy, pyramidal weakness, brisk tendon jerks and the plantar responses are extensor. Sensory abnormalities were observed only in the two eldest members and consisted of mild impairment of position and vibration sense. A sural nerve biopsy showed loss of large diameter fibres and uniformly short internodal lengths as is usually found in Friedreich's ataxia. However, the electrophyisological findings of retained sensory action potentials and reduced motor conduction velocities contrast with those of Friedreich's ataxia. Post-mortem examination of one of the affected members revealed spinal cord pathology similar to that seen in Friedreich's ataxia with degeneration of the dorsal columns, and spinocerebellar and corticospinal tracts although the loss of Purkinje cells in the cerebellum was greater than is usually seen in that condition.


Semantic access dyslexia.

An analytical investigation of the residual reading capacities of a single patient with dyslexia without dysgraphia is reported. Both his ability to name and to comprehend letters and words were severely impaired. The major finding of this investigation was AR's striking capacity for categorizing words he could not read. In addition there was evidence of semantic priming effects. Thus AR was frequently able to achieve partial comprehension of words he could not read. The orthodox interpretation of the dyslexia without dysgraphia in terms of a disconnection syndrome is shown to be inappropriate, at least for the present case, where the deficit appears to be within the semantic domain; it is argued that this type of dyslexia is due to an impairment in accessing semantic information.


Neurofibrillary degeneration on Guam: frequency in Chamorros and non Chamorros with no known neurological disease.

In a neuropathological study of the brains of 69 members of the Guamanian Chamorro population without known evidence of dementia, parkinsonism or amyotrophic lateral sclerosis, the incidence and severity of neurofibrillary degeneration was determined in relation to age at death. It was found that neurofibrillary degeneration is present at an earlier age than has been reported for a comparable population in Japan, and much earlier than reported for two similarly comparable English populations. Our data suggests that neurofibrillary degeneration is the common denominator of the Guam neurological syndromes of parkinsonian dementia, amyotrophic lateral sclerosis and dementia without parkinsonism. This conclusion would imply that the aetiological factor of neurofibrillary degeneration is more widely dispersed in the population than suggested by the cases of parkinsonian dementia and amyotrophic lateral sclerosis alone. Both sexes were equally affected while clinical parkinsonian dementia is three times more frequent among males. The sample data suggests a positive association with the amyotrophic lateral sclerosis-parkinsonian dementia rate in village of birth and residence, and also with family history; the results in the small subsamples are not significant. Senile plaques were found in few control cases in this study, just as there has been a relative absence of senile plaques in cases of parkinsonian dementia. In a small group of Caucasians who had spent many of their adult years on Guam, the frequency of neurofibrillary degeneration in relationship to age was comparable to that in the English populations.


The importance of knowing our own presuppositions.

This essay is in two parts. In the first part, consideration is given to specific issues raised in the preceding article, stressing two considerations. First, although Dr. Hughes disclaims an essentialist position, he in fact argues consistently for a classification of nerve cells based on key, essential features; except where, briefly, he argues for a numerical taxonomic approach. He apparently has not understood the hypothetico-deductive approach proposed by us. Second, he has not given consideration to important biological aspects of the problem of cell classification, in particular to the significance of variation of properties both within groups of cells and between corresponding groups. In the second part we argue that underlying the exchange of specific criticisms are differences in scientific methodology. We attempt to identify these differences, and to relate them to the present discussion. We hope that this will help focus subsequent discussion on the central issues involved and we argue for increased awareness on the part of neurobiologists of our own presuppositions about how science works.


Ultrastructural effects of 4-aminopyridine on the presynaptic membrane in the rat spinal cord.

The effects of 4-aminopyridine (4-AP, 1 mg/kg, i.v.) on the ultrastructure of synapses in the ventral horn of the spinal cord were examined in rats anesthetized with 50 and 100 mg/kg, i.p., pentobarbital sodium and alpha-chloralose respectively. The presynaptic membrane of the 4-AP-treated animals, in both S- and F-type synapses, was wrinkled and gave frequently rise to omega-shaped profiles. However, it was not prominently lifted in comparison with the controls. In both extracellular (EF) and protoplasmic fracture faces (PF) of freeze-etched replicas, the frequency of the presynaptic membrane modulations (PMM) per unit area rose significantly under the influence of 4-AP. The ratio of open (crater-like) to total PMM in EF increased almost twice under the experimental condition. No differential 4-AP effects were seen between pentobarbital- and chloralose-treated animals. The morphological evidence is consistent with electrophysiological data showing that 4-AP facilitates the transmitter release at synaptic endings.


Effect of cyclic changes in environmental lighting and ambient temperature on the daily rhythm in melatonin excretion by rats.

Melatonin excretion was measured by radioimmunoassay in 6 h or 12 h urine specimens from individual control rats and from animals previously blinded by bilateral orbital enucleation. Among sighted rats, the rate of melatonin excretion was greatest during the daily 12 h of darkness (1.44 +/- 0.06 ng/12 h dark period vs. 0.53 +/- 0.07 ng/12 h light period; P less than 0.001). Moreover, greater quantities of melatonin were excreted in the latter half of the dark period than in the first half (e.g. 0.55 +/- 0.08 ng/first 6 h vs 0.97 +/- 0.05 ng/second 6 h; P less than 0.001). When the onset of the daily light period was shifted forward by 12 h, 5--7 days were needed for the daily rhythm in melatonin excretion to become re-entrained to the new light--dark cycle. Among blinded rats, the rate of melatonin excretion also varied rhythmically; however, the rhythm was neither synchronized with the light-dark cycle nor influenced by alterations in the lighting schedule. Similarly, artificial cycles in environmental temperature were not effective in entraining the daily rhythm in melatonin excretion among blinded rats.


The development of some peripheral and central auditory responses in the neonatal cat.

The development of cochlear nerve action potential thresholds at different frequencies (AP audiograms) and inferior colliculus (IC) single unit thresholds and tuning was examined in barbiturate-anaesthetized kittens. AP thresholds decreased over the whole frequency spectrum during the first 5 weeks of life. Thresholds to high-frequency stimulation remained higher in 7-week-old animals than in adults. These results are in contrast to previous reports which have suggested that the AP response and gross cochlear anatomy are mature by the end of the second week. These differences may be due to the fact that the AP audiogram technique provides a measure of the activity of discrete regions along the cochlear partition. IC units in animals younger than 3.5 weeks had significantly elevated thresholds and broader tuning than those of the adult cat. Comparison of AP audiogram and IC unit thresholds in the adult revealed that these indices show similar frequency-dependent sensitivity. The slower maturation revealed by the AP audiogram may be due to the greater number and/or synchrony of cochlear nerve discharges needed to produce the gross AP. If this were the case, perception of suprathreshold sounds might not develop as quickly as thresholds for sound detection.


Partial interocular transfer of brightness and movement discrimination by split-brain cats.

Interhemispheric transfer of discriminations of brightness and direction of movement, two types of stimuli which may be processed by midbrain visual areas, was compared to transfer of control patterns in cats with sections of the optic chiasm and forebrain commissures. Transfer in these split-brain cats was further compared to transfer in partially split-brain cats with sparing of either the splenium of the corpus callosum or the anterior commissure. An intact splenium was necessary for high levels of interhemispheric transfer of all of the discriminations, which implies a prominant role for cortical mechanisms in such tasks. However, animals with complete section of the corpus callosum often showed partial interocular transfer of both brightness and movement discriminations, which may reflect a limited but selective participation of subcortical areas in visual perception. Cats in which the anterior commissure was spared did not show greater transfer on any of these tasks than did cats with section of both callosum and anterior commissure.


Variability in maps of identified neurons in the sea lamprey spinal cord examined by a wholemount technique.

A technique is described for preparing toluidine blue-stained wholemounts of lamprey spinal cords. By this technique virtually all the neurons in the spinal cord can be studied with respect to their soma size and shape, their primary dendrites, and sometimes secondary dendrites and proximal portions of the axon. Several cell types previously studied physiologically and described by others in cross section are described in wholemounts. These are dorsal cells, giant interneurons, edge cells and lateral cells. In addition, several unique cell types are noted in wholemount which were previously unremarked upon. These include obliquely oriented bipolar cells, trident-shaped cells located mostly in the rostral two-thirds of the spinal gray column, and small neurons with cell bodies in the dorsal and ventral axon tracts. Edge cells, which had previously been described as having large cell bodies close to the lateral edge of the lateral axon tracts with large medially oriented dendrites, are shown to be quite heterogeneous in size, location of soma and dendritic tree configuration. By use of the wholemount technique, 4 spinal cords of large sea lamprey larvae, close to transformation, were mapped for lateral cells, giant interneurons and dorsal cells. Considerable variability was noted in numbers and locations of these cells. The possible significance of this finding for the development of the vertebrate nervous system is discussed.


Synaptic density in human frontal cortex - developmental changes and effects of aging.

Density of synaptic profiles in layer 3 of middle frontal gyrus was quantitated in 21 normal human brains ranging from newborn to age 90 years. Synaptic profiles could be reliably demonstrated by the phosphotungstic acid method (Bloom and Aghajanian) in tissue fixed up to 36 h postmortem. Synaptic density was constant throughout adult life (ages 16--72 years) with a mean of 11.05 X 10(8) synapses/cu.mm +/- 0.41 S.E.M. There was a slight decline in synaptic density in brains of the aged (ages 74--90 years) with a mean of 9.56 X 10(8) synapses/cu.mm +/- 0.28 S.E.M. in 4 samples (P less than 0.05). Synaptic density in neonatal brains was already high--in the range seen in adults. However, synaptic morphology differed; immature profiles had an irregular presynaptic dense band instead of the separate presynaptic projections seen in mature synapses. Synaptic density increased during infancy, reaching a maximum at age 1--2 years which was about 50% above the adult mean. The decline in synaptic density observed between ages 2--16 years was accompanied by a slight decrease in neuronal density. Human cerebral cortex is one of a number of neuronal systems in which loss of neurons and synapses appears to occur as a late developmental event.


Development of high affinity choline uptake and associated acetylcholine synthesis in the rat fascia dentata.

The ontogenic development of hemicholinium-sensitive, high affinity choline uptake and the synthesis of acetylcholine from exogenous choline have been studied in particulate preparations of the rat fascia dentata. Between 6 days of age and adulthood the rate of high affinity choline uptake increases 3-fold, when expressed with respect to protein, and 125-fold, when expressed independently of protein. This process develops most rapidly during the period around 16-17 days of age, similar to the ontogenesis of choline acetyltransferase activity. This observation supports the idea that cholinergic septohippocampal boutons develop mainly at this time. Unlike choline acetyltransferase activity, the velocity of high affinity choline uptake increases to as much as 161% of the adult value at about 30 days of age. It is suggested that at 25-31 days of age a relatively high endogenous septohippocampal firing rate increases the rate of choline uptake. At 6 days of age we detected no synthesis of acetylcholine from the accumulated choline. Uptake-synthesis coupling develops mainly between 6 and 13 days of age, earlier than any other presynaptic cholinergic property. Acetylcholine synthesis from exogenous choline develops in paralled with high affinity choline uptake, but developmental increases in uptake velocity result in comparable increases in synthesis rate only after a delay of several days. Some limiting factor other than choline acetyltransferase activity appears to link the accumulation of exogenous choline to acetylcholine synthesis during development.


Protein and RNA synthesis in kainic acid-injected striata.

Injections of kainic acid into rat neostriata destroy neuronal soma in the injected area. Kainic acid-injected neostriata show a significant increase (as compared with control) in the incorporation in vitro of label from radioactive leucine into the TCA-insoluble protein fraction at all time periods studied (from 1 to 80 days after the kainic acid injection), with the greatest stimulation ((6-7-fold) occurring between the third and eighth day. At 1-5 days there was also increased incorporation in vitro of label from uridine into RNA. The increased protein synthesis is probably due to the astrocytes which invade the injected area and are still seen in electron microscopic studies 2-3 months after the injections.


Effect of pentobarbitone on the spontaneous efflux of gamma-amino acids from rabbit retina.

The effect of pentobarbitone on the spontaneous release of radioactivity from rabbit retinas preloaded with [3H]GABA, [3H]DABA, [3H]beta-alanine and [3H]glycine was studied. In high concentration of pentobarbitone (10(-3)M) the rate of spontaneous efflux of neuronal [3H]GABA, [3H]DABA and [3H]beta-alanine was reduced but not that of [3H]glycine. Glial release of [3H]GABA was much less influenced. At lower concentrations (10(-4)-10(-5)M) there was an initial increase in the release of [3H]GABA, [3H]DABA and [oH]beta-alanine followed by a decrease, indicating several components in the release system for the amino acids.


Retinohypothalamic tract development: alteration by suprachiasmatic lesions in the neonatal rat.

The suprachiasmatic nucleus (SCN), the terminal nucleus of the retinohypothalamic (RH) tract, was ablated electrolytically in 2-day-old rats. Since previous studies have demonstrated that the earliest retinal fibers arrive on postnatal day 3 to 4 (refs. 4, 17), the lesions were inflicted prior to the formation of retinal connections. At day 25, [3H]proline was injected into the eye and autoradiography performed to determine if developing RH fibers would exhibit plasticity and innervate any hypothalamic nucleus other than the SCN. No evidence was found for the formation of anomalous retinal connections after complete, bilateral SCN lesions. Incomplete lesions, however, result in some alteration in the distribution of retinal fibers to the SCN. If a part of the caudal three-quarters of the SCN remains, RH projections form in a pattern dependent upon the size and location of the intact SCN fragment. These results indicate a high degree of specificity in developing RH fibers for their normal target tissue and a minimal capacity for plasticity in contrast with the various forms of neuronal reorganization observed after early destruction of other components of the visual system.


Neonatal suprachiasmatic nucleus lesions: effects on the development of circadian rhythms in the rat.

Previous studies of the effects of suprachiasmatic nucleus (SCN) destruction and visual pathway transections in adult rodents have revealed the primary significance of the SCN and the retinohypothalamic (RH) projection in the generation and entrainment of circadian rhythms. In the present study we found that complete ablation of the SCN in 2-day-old rats, prior to its innervation by the RH projection, permanently eliminates circadian rhythms in spontaneous locomotor activity and drinking; activity and drinking appear randomly distributed over the light-dark cycle. In addition, females exhibit long periods of constant vaginal cornification and an absence of normal estrous cycles. These effects are independent of the animal's visual status; that is, they occur in blinded as well as sighted animals. Incomplete SCN lesions results in partial disruption of rhythmic functions such as damping of circadian rhythms in activity and/or drinking, irregular estrous cycling, and/or complete disruption of only one or two of these measures of rhythmicity. The absence of spared functions after early SCN destruction is consistent with the high degree of specificity for the SCN exhibited by developing RH fibers and further emphasizes the significance of the SCN in circadian rhythm generation. Neither morphological nor functional plasticity has been found following neonatal ablation of the SCN in the rat.


Age-dependent effects of 6-hydroxydopamine on locomotor activity in the rat.

This experiment examined the effects on locomotor activity of intraventricular 6-hydroxydopamine (6-OHDA) administered to developing and adult rats. 6-OHDA was administered subsequent to pargyline treatment at 3 and 6 days of age; or 6-OHDA was administered subsequent to desmethylimipramine (DMI) treatment (6-OHDA/DMI) at 3 and 6 days of age, 11 and 14 days of age, 20 and 23 days of age, or 46 and 48 days of age. Locomotor activity of vehicle-treated rats assessed in stabilimeter cages peaked between 14 and 16 days of age and subsequently declined to levels characteristic of the adult. Treatment with pargyline and 6-OHDA at 3 days of age, or 6-OHDA/DMI at 3 and 6 or 11 and 14 days of age, did not alter the early rise in locomotor activity but prevented the decline in activity normally seen during the third and fourth weeks of life. When tested as adults, locomotor activity was greater in rats that had been treated with 6-OHDA/DMI at 3 and 6 and at 11 and 14 days of age than in those that had been treated at 20 and 23 days of age. Treatment with 6-OHDA/DMI at 46 and 48 days of age was without significant effect on locomotor activity. 6-OHDA (with pargyline pretreatment) produced large decreases in NE content in telencephalon and diencephalon and in dopamine (DA) content in striatum. 6-OHDA-DMI also produced large decreases in DA content in striatum and, in some of the treatment groups, only small decreases in norepinephrine (NE) content in telencephalon, diencephalon, and brain stem. These data suggest that the maturation of neuronal systems utilizing dopamine as a neurotransmitter is essential for the suppression of locomotor activity normally seen during development. The data further suggest that dopamine depletion per se does not lead to increased locomotor activity, but rather it is the destruction of dopamine-containing fibers prior to the normal period of locomotor suppression that increases locomotor activity.


Lesion-induced plasticity of high affinity choline uptake in the developing rat fascia dentata.

After removal of the perforant path input to the rat fascia dentata at the age of 11 days, cholinergic septohippocampal fibers invade the denervated area. We have examined the effect of this lesion on hemicholinium-sensitive, high affinity choline uptake and its coupling to acetylcholine synthesis, specific properties of the septohippocampal input. Removal of the ipsilateral perforant path fibers increased the velocity of high affinity choline uptake by dentate particulate preparations, usually within 1 day. Studies conducted 5--104 days after operation showed a consistent 50--65% elevation in the molecular (denervated) layer. In contrast, the choline uptake rate in the granular layer eventually decreased slightly. Calculation of choline uptake rates independently of protein (per whole region) revealed that fasciae dentatae from operated and control sides accumulated choline at approximately equal rates, but on the operated side a greater percentage was transported by structures from the molecular layer and a lesser percentage by those from the granular layer. The rate of acetylcholine synthesis from exogenous choline increased to the same extent as high affinity choline uptake from 3 days after operation onwards. The changes in high affinity choline uptake and acetylcholine synthesis coincided spatially and temporally with the reactive growth of septohippocampal fibers. Our results support the view that a perforant path lesion during development permanently alters the distribution of functional septohippocampal boutons in the fascia dentata. Acetylcholine synthesis is regulated to the same extent by high affinity choline uptake in the anomalous boutons as in normally located boutons.


Changes in canine postural control after injury to anterior vermal cerebellum.

For a preliminary exploration of cerebellar influences on postural control, dogs were trained to stand quietly erect. Posture was perturbed by sinusoidal movement of the supporting table while the dogs were sighted and while they were blindfolded or stimulated by sinusoidal optokinetic stimuli. Postural responses were evaluated by measuring the relative amplitude of pelvis movement over a series of perturbing frequencies; frequency response descriptions were derived. Lesions of the cerebellar vermis in 3 dogs involved the cortex of lobules V and VI, of lobules IV, V and VI, and of lobules IV--VII plus damage to the medial portion of nucleus fastigius. The two smaller lesions degraded the animal's tracking ability under all three conditions temporarily with extensive but incomplete compensation in 14--21 days. The larger lesion effectively and permanently eliminated the animal's ability to track table or visual field motion. Elimination of visual cues by blindfolding or perturbing the posture with optokinetic stimuli significantly exaggerated the control deficiencies produced by the lesions. It is concluded that the visual input to the cerebellar vermis finds expression through postural control channels.


Histogenesis of the superior colliculus of the albino rat: a tritiated thymidine study.

The pattern of generation of neurons in the albino rat superior colliculus has been studied in adult and fetal material. Neurons are generated between embryonic days 12 to 17, with rostrolateral colliculus in advance of caudomedial parts. More of the cells contributing to the deeper layers are generated early, while more of the later generated cells are located superficially. The cells of individual laminae are not formed on specific days as in the cortex, nor are the complicated gradients described previously for the chick optic tectum evident. While the largest cells (found deep in the colliculus) are among the first formed and the small marginal cells among the last, there is in general a broad range of cell size being generated at any one time. The observed patterns are consistent with the concept of simultaneous production of several cell types from the ventricular epithelium on any given day. Studies of material at short times after [3H]thymidine injection allow correlation of the time of arrival of cells in their appropriate layer with time of arrival of afferents. In addition they suggest that factors controlling the final placement of cells in the mature nervous system is a very complex process and may involve some form of intercellular recognition.


Penetration of grafted astrocytic scars by regenerating optic nerve axons in Xenopus tadpoles.

The following study was performed in order to determine the effect of a dense glial scar upon the outgrowth of neurites in the regenerating optic nerves of Xenopus tadpoles. Glial scars, primarily comprised of hypertrophic astrocytes, were formed in the optic nerves of postmetamorphic, juvenile Xenopus by unilateral enucleation. After 25--40 days, segments of glial scar tissue were then grafted near the cut retinal stumps of the transected optic nerves in stage 54--56 tadpoles. Within 7--10 days bundles of unmyelinated axons were seen among the cytoplasmic processes of the implanted astrocytes, and many of the fibers had traversed the entire extent of the graft by 7--10 days. The results indicate that in this regenerating system an extremely dense glial scar, formed by mature, hypertrophic astrocytes, does not represent a major obstacle to axonal outgrowth. These observations are discussed in relation to the problem of glial scarring and the general failure of regeneration in the mammalian central nervous system.


Current-voltage relationships of repetitively firing neurons.

The current-voltage curves of repetitively firing neurons show non-linearities in the subthreshold region. Microsurgically isolated molluscan neuron somata were studied under voltage clamp using ramp voltage command signals. During the depolarizing 1/2 cycle a region of negative slope conductance was observed. Ion substitution experiments suggest that this results from non-inactivating or slowly inactivating Na+ and Ca2+ currents. The hyperpolarizing 1/2 cycle reveals a hysteresis effect which results at least in part from a Ca2+ activated 5+ current. Similar characteristics have been described in bursting neurons. Their occurrence in the non-bursting neurons studied here shows that they are not unique to this class of neurons and suggests that their primary contribution is to create electrical instability necessary for repetitive firing.


Is there an active mechanism limiting the influence of the sympathetic system on the cerebral vascular bed? Evidence for vasomotor escape from sympathetic stimulation in the rabbit.

The influence of the cervical sympathetic chain on cerebral circulation in the rabbit was studied by means of 3 complementary techniques. Two dynamic techniques involving chronically implanted probes were used: blood flow in the caudate nucleus (CN) was measured by thermal clearance; tissue PO2 and PCO2 in the same structure were measured by mass spectrometry. Other variables measured continuously and simultaneously included arterial blood pressure (BP), PaO2 and PaCO2. The third technique was a tissue sampling method based on the Fick principle and using 14C1 ethanol as tracer. Blood flow in 7 regions was measured at stable BP, PaO2 and PaCO2. Stimulation of the sympathetic chain at 15 Hz induced mean maximal decreases in CN blood flow of 23.9% (thermal clearance) and 24.4% (ethanol technique). Mean decrease of PO2 in the CN at 15 Hz was 16.6%. Significant falls in blood flow were observed with the ethanol technique in all 7 structures measured. During prolonged stimulation (greater than 1 min) CN blood flow and PO2 were found to escape towards the baseline level, which was sometimes even exceeded during the stimulation (blood flow). Stimulation frequency had only a very moderate influence on the rate of escape, and no evidence of a metabolic mechanism was found, although injection of barbiturate decreased the escape. These results are discussed with respect to the conflicting evidence on the effects of sympathetic stimulation in the brain, and to possible mechanisms for the escape phenomenon.


Electron microscopic identification of cerebellopontine axon terminals in the opossum.

Following unilateral cerebellar nuclear ablation or transection of the brachium conjunctivum, degenerating axon terminals were identified within the pontine nuclei of adult opossums. Most frequently observed was a category of large boutons (1.5-7.5 microns) exhibiting an early filamentous reaction (1-5 days survival) and later becoming electron dense and shrunken (9-12 days survival) while being engulfed by phagocytic elements. Such boutons characteristically were found nestled within a cluster of spine-like projections taking origin from somata as well as proximal and intermediate dendrites. A smaller variety of dark degenerating boutons (0.5-2.0 micron) was observed after survival periods of intermediate length (6-10 days) and although there was some overlap in size with the smallest filamentous boutons, the majority (71%) were clearly less than 1.5 micron in their greatest dimension. The small dark boutons formed synaptic contacts only with the shafts of intermediate and distal dendrites rather than the claw-like dendritic complex apposed to the large filamentous degenerating boutons. Because of this difference in postsynaptic locus and their small size it was suggested that such boutons might represent the terminals of a second population of cerebello-pontine axons. Such observations lead to the hypothesis that the large filamentous endings contacting the distinctive claw-like somal or dendritic projections from axons of relatively large cerebellar nuclear neurons which also project rostrally to the red nucleus and thalamus where they form similar boutons and synaptic complexes. On the other hand, the small dark boutons may have arisen from small projection-type cerebellar nuclear neurons, the majority of whose axons project caudally to the inferior olive after contributing a relativley small number of collateral branches to the pontine nuclei.


Anin vivo method to prepare normal Schwann cells free of axons and myelin.

A viable population of undifferentiated Schwann cells may be prepared from chronically denervated peripheral nerves. Nerve transection stimulates a sequence of cellular events in distal stumps leading to removal of axons and myelin, and proliferation of Schwann cells. Sealing the ends of nerve stumps prevents reinnervation and leaves daughter Schwann cells residing in longitudinal columns. Schwann cells may be harvested from the endoneurial tissue of the nerve stumps 5-12 weeks after nerve transection. Unlike myelinating cells prepared from intact tissue, where function has been specified by associated axons, Schwann cells obtained from denervated stumps are functionally naive. Their usefulness in analyzing axonal regulation of myelinogenesis and mitosis is therefore suggested.


Septo-hippocampal pathway necessary for dentate theta production.

In acute experiments in urethane-anaesthetized rabbits a small lesion at the septo-hippocampal border, from 0.8 to 1.5 mm from the midline, abolished theta activity ipsilaterally. This lesion severed fibres from the lateral part of the medial septal nucleus. Lesions of the main body of the fimbria or the dorsal fornix, alvear bundle and perforant path or the hippocampal commissures failed to change the dentate theta activity. Theta activity also survived the establishment of a 2 mm wide 'gate' near the rostral pole of the hippocampus; the gate was produced by cutting the main body of the fimbria and medially adjoining tissue and the dorsal fornix and laterally adjoining tissue. Cuts behind the 'gate' showed successive reduction of the dentate theta when the lesion passed beyond a threshold depth of about 1.5 mm. The degree of theta reduction appeared dependent upon the amount of the hippocampal tissue destroyed below this level. Thus, the fibres of importance for theta production seem to run through a bottleneck just behind the medial septum. Their further course is found in the basal part of the fimbria on its medial aspect and the adjoining parts of CA3 (lower blade) and hilus of the dentate fascia. Because the whole of this area had to be destroyed to block all theta activity, it is suggested that the fibres of importance for theta production are relatively dispersed within this region.


The spontaneous firing patterns of forebrain neurons. IV. Effects of bilateral and unilateral frontal cortical ablations on firing of caudate, globus pallidus and thalamic neurons.

To assess the effects of partial deafferentation of the neostriatum on spontaneous neuronal activity in the basal ganglia and related thalamic nuclei, ablations of frontal cortex were carried out in adult cats. Postoperative measures of interspike intervals of single neurons in the caudate nucleus, globus pallidus and ventral anterior-ventral lateral complex of the thalamus revealed a slowing of neuronal firing in these structures as compared with non-lesioned controls. The fact that deafferentation by cortical damage produces changes in neuronal firing in target neurons of the striatum (globus pallidus) and in thalamic neurons at least two synapses removed from the striatum is noteworthy. The possible extent to which these results might have been influenced by reduction of cortical inputs to or denervation of the thalamus is discussed.


Noradrenaline, fear and extinction.

It has been suggested that noradrenaline in the central nervous system is involved in fear and anxiety. To test this postulate extensive depletion of ascending noradrenaline systems was accomplished by intracerebral injection of the selective neurotoxin 6-hydroxydopamine. Fear and anxiety were assessed using a Sidman avoidance task and a conditioned emotional response paradigm. No alteration in fear motivated acquisition learning of either of these tasks were detected. Resistance to extinction was seen on the conditioned emotional task, perhaps because of its continuously reinforced nature, but not on the Sidman avoidance, perhaps as a consequence of the reinforcement contingencies which render this task more similar to a partially reinforced schedule. No evidence for a role of ascending noradrenaline systems in fear or anxiety was hence obtained, but a further demonstration of a role in extinction processes was found.


Effects of endorphins on single myenteric neurons.

Methionine-enkephalin, leucine-enkephalin and beta-endorphin were applied in known concentrations to an in vitro preparation of myenteric neurons from the guinea-pig ileum. All 3 substances caused a rapid, reversible and dose related inhibition of the firing of myenteric neurons induced and recorded with extracellular suction electrodes. This inhibition of firing occurred at low agonist concentrations (1-300 nM) and was reversed by naloxone and a benzomorphan narcotic antagonist. The inhibition persisted in solutions which were completely free of calcium ions -- thus indicating that the observed effect is taking place directly on the neuron from which the recording is made, and that calcium ions are not required for this inhibitory action of endorphins on neuronal firing.


Some temporal output properties of color opponent units in the ground squirrel retina.

Responses of BG-G units to equal energy stimuli of different wavelengths reveal a tonic to phasic pattern of responses in which short wavelengths (blue) evoke tonic activity, medium wavelengths (green to yellow) evoke phasic activity and intermediate wavelengths evoke in-between patterns. The patterns correlate with wavelength but are relatively insensitive to intensity. Output patterns of BG-G cells to white and to monochromatic light at the animal's neutral point are almost identical, and the pattern identities may be a neural correlate to the behavioral phenomenon of the neutral point.


Cholinergic binding sites in rat hippocampal formation: properties and ontogenesis.

The hippocampal formation of the rat contains two types of membrane-bound cholinergic binding sites, as revealed by specific binding of [3H]quinuclidinyl benzilate (QNB) or of a-[125I]bungarotoxin (a-Btx). The sites differ in pharmacological profile, sensitivity to detergents and ontogenesis. The major binding site (about 17 pmol per adult hippocampus) is of a muscarinic nature, and binds [3H]QNB with an on-rate of 2 x 10(6) M-1 sec-1 and an apparent KD of 0.4 nM. This binding is displaced by low concentrations of muscarinic ligands but not of nicotinic ligands. The earliest increase in binding level is detected at about day 4 postnatal and a sharp increase in total binding takes place between days 10 and 15. Total binding continues to increase gradually about 3-fold until an age of about 7 weeks, at a rate resembling that of acetylcholinesterase. a-Btx-binding sites (about 0.6 pmol per adult hippocampus) display a nicotinic profile with an on-rate constant for a-[125I]Btx of 6 x 10(4) M-1 sec-1 and an apparent KD of 2 nM. Ontogenesis of these sites clearly differs from that of muscarinic sites and acetylcholinesterase. Absolute binding reaches mature levels at an age of 12--14 days postnatal, and binding per tissue protein is higher during the first postnatal days than at maturity. It appears that the level of toxin-binding sites attains mature values before the major synaptogenetic events in the area are completed.


Adrenaline levels in brain stem nuclei and effects of a PNMT inhibitor on spontaneously hypertensive rats.

The adrenaline content of specific brain stem areas was decreased in young (4 week-old) but not in adult (14 week-old) SHR. Some of these areas also showed increased PNMT activity, indicating a possible enhanced release or metabolism of adrenaline early in the development of the hypertension. Dopamine and noradrenaline levels, on the contrary, were not changed either in young or adult animals. Administration of a PNMT inhibitor to adult SHR resulted in a decrease of the blood pressure in SHR to control levels. These observations support the hypothesis of a participation of adrenergic mechanisms in the development of genetic hypertension, and indicate the possibility for the use of PNMT inhibitors as hypotensive agents.


Electrophysiological and biochemical responses of noradrenergic neurons to a non-amphetamine CNS stimulant.

Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whg rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those  which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.


The dorsal bundle extinction effect:dependence on subtle changes in acquisition.

Destruction of the ascending noradrenergic innervation to the forebrain in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine (4 microgram in 2 microliter injected bilaterally into the dorsal bundle in the mesencephalon) was found to cause resistance to extinction of a continuously reinforced lever press response. However, this effect occurred only if the lesion were present during acquisition training on the reinforced schedule and not if intact animals were trained and the lesion inflicted after completion of acquisition training and just prior to the extinction phase. Thus, the behavioural effect that manifests itself during extinction appears to be due to subtle changes in the acquisition learning process. This is consistent with the predictions of an attentional theory of noradrenergic function and appears to exclude most other suggested explanations of the dorsal bundle extinction effect.


Characterization of proteins associated with nuclear ribonucleoprotein particles by two-dimensional polyacrylamide gel electrophoresis.

Rat liver nuclear ribonucleoprotein particles were prepared by two different methods and defined as 40S ribonucleoprotein (40S RNP) and heterogeneous nuclear ribonucleoprotein (HnRNP) particles. The RNP particles were either solubilized in 8 M urea--6 mM 2-mercaptoethanol--20 mM glycine--20 mM Tris--HCl (pH 8.4) or subjected to removal of RNA by phenol extraction prior to solubilizing the proteins in the urea buffer. The proteins associated with 40S RNP and HnRNP were heterogeneous and very similar in their electrophoretic patterns when analyzed by two-dimensional PAGE, except a protein with molecular weight of 62 000 and an isoelectric point (pI) of 6.2 was present only in HnRNP particles. At least 12 major and 22 minor components could be identified in both preparations. The major proteins were found at pI values varying from 6.0 to 8.5 and with molecular weights from 32 000 to 42 000, and a group of proteins with molecular weight approximately 65 000 were more prominent in HnRNP than in 40S RNP. The other components were found mainly at pI ranges from 5.0 to 6.5 with molecular weights from 43 000 to 65 000. The phenol method extracted essentially all proteins associated with either 40S RNP and HnRNP, but was less effective in extracting a group of proteins with pI values from 5.0 to 5.5 and more efficient for proteins with pI values from 7.5 to 8.5. When chromatin proteins isolated by phenol extraction were compared with HnRNP particle proteins isolated by the same method, the electrophoretic mobilities of the HnRNP particle proteins were found to be identical with a fraction nonhistone chromatin proteins. The 40S RNP particles were further purified by metrizamide isopycnic density gradient centrifugation. The electrophoretic patterns of these proteins were very similar to those prepared by sucrose density gradient centrifugation. Therefore, we concluded that the proteins of RNP particles constituted part of the chromatin proteins.


Histochemical and cytochemical localization of acetylcholinesterase in retina and optic tectum of teleost fish.

The activity of cholinesterase and its cellular and subcellular localization were investigated in the retina and optic tectum of Eugerres plumieri and in the retina of Carassius carassius by means of radiometric, histochemical, and cytochemical procedures. In both fishes only the presence of acetylcholinesterase could be demonstrated. This study, besides confirming previous findings that acetylcholinesterase is located in the ganglion and amacrine cells of the retina as well as in the inner plexiform layer, in addition provides evidence that the enzyme is also present at the region of photoreceptor synapses between the cell bodies and apposing extensions of the horizontal cells of the same layer. The latter localization may indicate the involvement of a cholinergic mechanism at the functional contacts (transferapses) between the horizontal cells. In the optic tectum of Eugerres plumieri, histochemistry reveals fine distinguishable bands of acetylcholinesterase activity; two of the bands are quite sharply defined, whereas three others have rather a more diffuse appearance. The presence of these bands and their distribution may suggest a widespread distribution of cholinergic elements in the optic tectum.


Effect of phalloidin on actin proteolysis as measured by viscometry and fluorimetry.

Even at low concentration, phalloidin shows a marked protection of F-actin against the action of trypsin or pronase. G-actin is not protected at any concentration of phallodin. The kinetics of the proteolysis show that a change in the environment of tryptophan residues is preceded by disruption of the filamentous structure of F-actin.


Relationship between tissue levels of S-adenosylmethionine, S-adenylhomocysteine, and transmethylation reactions.

The concentrations of S-adenosylmethionine (AdoMet), S-adenosylhomocysteine (AdoHcy), and various methyltransferases were determined in the cerebrum, cerebellum, and liver of rats during development and aging. The liver contained from 3 to 7 and from 10 to 15 nmol AdoHcy per gram in young and adult rats, respectively. The AdoMet concentration was 60 to 90 nmol/g liver from rats of the same age and sex. It did not vary significantly with age. In the brain the AdoMet concentration was 45 to 50 nmol/g at birth and decreased to 20 nmol/ g tissue with maturity of the organ. The level of AdoHcy in this organ was less than 1 nmol/g tissue throughout the life-span of the rat. Since the ratio of AdoMet to AdoHcy is relatively high, the rate of methylation of histones, DNA, or phosphatidylethanolamine in the liver or brain was not significantly influenced by AdoHcy. Under normal nutritional conditions, the tissue concentration of AdoMet is far above the Km values of histone and phosphatidylethanolamine methyltransferases. The levels of activity of these enzymes in liver and brain did not correlated with the cellular concentration of AdoHcy. Thi histone methyltransferase activity was elevated in rapidly proliferating tissues and declined markedly in the absence of histone biosynthesis. Phosphatidylethanolamine methyltransferase activity was elevated during development of the liver. The specific activity of the AdoHcy hydrolase remained relatively constant in the rat brain and liver. The activity of this enzyme was 10 times higher in liver than in brain, yet the concentration of AdoHcy was much lower in the latter organ. The tissue levels of this compound are evidently dependent on the rates of removal of homocysteine and adenosine. Adenosine deaminase was present in the liver and brain at relatively high concentrations, particularly during development.


Effect of lysolecithin in solubilizing membrane-bound glycosyltransferases.

Microsomal membranes were solubilized by incubation with lysolecithin which caused considerable release of galactosyl- and N-acetylglucosaminyl-transferase into a high-speed supernatant fraction. With a critical concentration of lysolecithin (2.5 mg/10 mg protein in 1 mL microsome suspension), there was a maximal binding of radioactive lysolecithin to the sediment fraction obtained after high-speed centrifugation. Increase of lysolecithin concentration (above 2.5 mg/mL) in the incubation mixture caused a progressive release of the enzymes into the supernatant fraction. Lysolecithin binding to the membrane was greatly inhibited by 1 M NaCl, and high salt concentration also inactivated galactosyltransferase in the sediment, suggesting an electrostatic interaction between lysolecithin and membrane enzyme. In contrast, high NaCl concentration had no inhibitory effect on the enzyme activity in the sediment when the fraction was prepared by treatment with Triton X-100. Lysolecithin-treated microsomal sediment and supernatant galactosyltransferase was inactivated by oleoyllysophosphatidic acid but not by palmitoyllysophosphatidic acid or egg yold lysophosphatidic acid. Triton X-100 treated microsomal fractions were also similarly affected by different species of lysophosphatidic acid. The results suggested a similarity of interactions of lysophosphatidic fatty acyl species with lysolecithin and Triton-treated galactosyltransferase.


A structural basis for four distinct elution profiles on concanavalin A--Sepharose affinity chromatography of glycopeptides.

Twelve 14C-acetylated glycopeptides have been subjected to affinity chromatography on concanvalin A (Con A)--Sepharose at pH 7.5. The elution profiles could be classified into four distinct patterns. The first pattern showed no retardation of glycopeptide on the column and was elicited with a glycopeptide having three peripheral oligosaccharide chains: (abstract:see text). Such glycopeptides have only a single mannose residue capable of interacting with Con A--Sepharose; an interacting mannose residue is either an alpha-linked nonreducing terminal residue or an alpha-linked 2-O-substituted residue. The second type of profile showed a retarded elution of glycopeptide with buffer lacking methyl alpha-D-glucopyranoside (indicative of weak interaction with the column) and was given by glycopeptides with the structures: (abstract: see text) where R1 is either H or a sialyl residue. The third profile type showed tight binding of glycopeptide to Con A--Sepharose and elution as a sharp peak with 0.1 M methyl alpha-D-glucopyranoside; glycopeptides giving this pattern had the structures: (abstract: see text) where R2 is either H, glcNAc, Gal-beta 1,4-GlcNAc, or sialyl-Gal-beta 1,4-GlcNAc. These glycopeptides all have two interacting mannose residues, the mimimum required for binding to the column; one of these mannose residues must, however, be a terminal residue to obtain tight binding and sharp elution. The fourth profile type showed tight binding of glycopeptide to the column but elution with 0.1 M methyl alpha-D-glucopyranoside resulted in a broad peak indicating very tight binding; glycopeptides showing this behaviour had the structures: (abstract: see text) where R3 is either GlcNAc,Gal-beta 1,4-GlcNAc, or sialyl-Gal-beta 1,4-GlcNAc. Therefore it can be concluded that although a minimum of two interacting mannose residues is required for binding to Con A--Sepharose, the residues linked to these mannoses can either strengthen or weaken binding to the column.


Heterogeneous catalysis by phospholipase A2: formulation of a kinetic description of surface effects.

The kinetics of hydrolysis of aqueous dispersion of long-chain, saturated phosphatidylcholines (PC) catalysed by Crotalus atrox phospholipase A2 (PLA) have been analyzed, and a reaction mechanism proposed which takes surface effects into account. PLA is proposed to form an enzyme-substrate complex with surface substrate molecules, thereby undergoing a conformational change which exposes sites that interact with the lipid surface. After a hydrolytic event, the enzyme can either desorb from the surface (path 1), or diffuse along the surface to an adjacent substrate molecule (path 2). The path 1 dominated mechanism leads to Michaelis-Menton steady-state kinetics, and characterizes hydrolysis of gel phase PC. Evidence for saturation of the surface with PLA was obtained at high enzyme concentrations. The path 2 mechanism dominates when the desorption rate is very small; this mechanism describes hydrolysis of liquid crystalline phase PC and is characterized by an initial burst of hydrolysis followed by a very slow reaction. The velocities in these two phases of the reaction are independent of bulk PC concentration. When gel and liquid crystalline PC phases coexist, as in mixtures of dimyristoyl- and distearoyl-PC, the liquid crystalline phase is preferentially hydrolysed. Products of the reaction (lyso-PC and fatty acid) stimulated hydrolysis, apparently by stimulating desorption of PLA. The desorption rate constant appears to be a linear function of the surface concentrations of lyso-PC and fatty acid. The proposed model describes hydrolysis progress curves extremely well and is consistent with current ideas on the mechanism of catalysis by this enzyme.


Experimental oral and nasal transmission of rabies virus in mice.

Weanling female white Swiss mice were exposed to challenge virus standard rabies virus and street virus isolates from various domestic and wild animals. Virus was given free choice as suspension or as infected mouse brain by stomach tube, by single injection of suspension into the oral cavity of unanesthetized mice, by repeated injection into the oral cavity of anesthetized mice and by single application to the external nares of anesthetized mice. Challenge virus standard virus in mouse brain suspension and a suspension of skunk salivary glands infected with street virus (titers greater than or equal to 10(6)MICLD50/0.03 ml) consistently produced high rates of infection in mice exposed intranasally, low to high rates of infection in mice exposed by forced feeding and other artificial methods of oral exposure and very low rates of infection when given free choice. Street virus isolates passaged intracerebrally in mice had titers less than or equal to 10(4.5) MICLD50/0.03 ml and rarely caused rabies in mice exposed orally or nasally by any method. The results indicate that with the isolates used, virus of high titer (greater than or equal to 10(6)MICLD50/0.03 ml) is required to consistently produce infection in mice by the nasal route and that the mucosa of the nasal cavity probably is the chief route of infection even after oral administration.


Anastomoses of intestinal tract as a sequela to rectal stricture in swine.

Rectal stricture with anastomoses of colon and/or small intestine to a spherical dilatation of the descending colon proximal to the stricture was observed in six swine. In three of these swine, feces bypassed most of the colon in passage from the small intestine to the dilated colon. Rectal stricture with an anastomosis of a loop of colon to the rectal stricture was observed in one pig where feces bypassed much of the stricture.


Prenatal infection following maternal exposure to porcine parvovirus on either the seventh or fourteenth day of gestation.

Intranasal and oral exposure of two gilts to porcine parvovirus on either the seventh or 14th day of gestation resulted in prenatal infection. Normal appearing fetuses and necrotic remnants of what were believed embryos and extraembryonic membranes were found when the gilts were necropsied seven weeks after exposure. The presence of masses of porcine parvovirus antigen throughout necrotic tissues of six of seven embryos, but not in any of the nine normal appearing fetuses suggested that embryonic death was due to porcine parvovirus.


Structural abnormalities of the X-chromosome in a heifer.

Structural chromosome abnormalities, some of them unusual, were found in 18 (36%) of 50 photomicrographed mitotic cells of a blood lymphocyte culture from a three month old Holstein heifer affected with chronic tympanism of the rumen. The aberrations involved more specifically the X-chromosome. The etiology of the anomalies and the cause of their X-chromosome propension are of unknown nature.


Brain viral persistence and myelin damage in nude mice.

Multiple foci of secondary demyelination were observed in the cerebellum of nude mice given two inoculations of avirulent Semliki Forest virus compared to single lesions seen in similarly treated Swiss A2G mice. The increased number of demyelinative plaques were attributed to brain viral persistence for 35 days in the nude mice with correspondingly low serum antibody titres. No neurological signs were observed in any of the mice.


The effect of vasoactive intestinal polypeptide on the urinary bladder and taenia coli of the guinea pig.

The effect of vasoactive intestinal polypeptide (VIP) on the contractile activity of the urinary bladder and taenia coli of the guinea pig has been investigated. In the urinary bladder VIP caused a weak contraction and a small potentiation of the nerve-induced contraction. In the taenia coli VIP caused a small relaxation and had no effect on the nerve-induced relaxation of the preparation. The present experiments provide no evidence that VIP fulfills a role as a neurotransmitter in the urinary bladder or taenia coli, but it could be a modulator of transmitter action in the urinary bladder.


Human lymphocyte migration in vitro: characterization and quantitation of locomotory parameters.

Using a time-lapse cinephotomicrographic technique, the locomotory paths taken by lymphocytes have been shown to satisfy the requirements for a continuous-time Markov chain analysis consisting of four directional states defined by the four quadrants of a Cartesian plane and state 0 in which the cells are stationary. The important parameters characterizing this path motion are the average time (waiting time) that a cell spends in each state and the state transition probabilites which, using the Markov model, allow the computation of the probability of the cells moving in a given direction. Our results show that lymphocytes moving alone on glass exhibit a random migration pattern.