Epiphyseal growth and osteoarthrosis in blotchy mice.

Blotchy mice which carry a gene causing inadequate cross-linking of collagen were investigated for the progress of epiphyseal growth and for the appearance of changes in the knee joints following cessation of growth. In male mice of the strain, which are hemizygous for the gene, early growth proceeded in a histologically normal fashion, although the metaphyseal bone was less abundant than usual. From the age of 3 1/2 months on, the animals developed osteoarthrosis of the knee joints and at the time of death at 5-6 1/2 months of age, 88% of the animals had osteoarthrosis. The findings are discussed with special reference to a possible role of the collagen of the articular cartilage in the pathogenesis of some forms of osteoarthrosis.


A simplified method for the isolation of sperm heads from the caput epididymidis of rodents and from ejaculated rabbit seminal plasma.

The present report describes a simple and rapid procedure to isolate highly purified sperm heads from mouse, rat and rabbit. The isolation procedure involves mincing of the caput epididymidis (CPE) of mice and rats to obtain a crude CPE suspension. This suspension is filtered to remove tubular fragments. The filtrate containing sperms and cellular contaminants is trypsinized, followed by sonication. To obtain rabbit sperm head suspension, ejaculated spermatozoa are briefly exposed to the cationic detergent CTAB-D, followed by trypsinization. Trypsin treatment of the suspension yields sperm heads and tails. The suspension containing sperm heads and tails is separated by discontinuous sucrose density gradient centrifugation. Highly purified and enriched sperm heads are recovered from the bottom of 2.5 M sucrose of the gradient. Enriched sperm heads contain less than 1% sperm tails.


The migration of lymphocytes across specialized vascular endothelium. III. Concanavalin A delays lymphocytes in normal traffic areas.

Radioactively labelled rat lymphocytes were treated in vitro with concanavalin A (con A) and injected intravenously into syngeneic recipients. By examining the blood and tissues at intervals from 30 min to 48 h after injection, it was confirmed that con A altered the distribution of lymphocytes. Comparison was made with the localization of alternatively labelled untreated lymphocytes injected into the same recipients and with untreated lymphocytes injected into other recipients. Within 1 h of injection there was a surplus of treated cells in the lungs and liver and deficits (of equal magnitude) in the blood, spleen and lymphonodes. By 24 h after injection there was a twofold surplus of treated cells in the spleen but a persisting deficit in lymphnodes. These perturbations can be ascribed to the prolonged retention of lymphocytes in normal sites of localization; there is no evidence that con A either hinders the migration of lymphocytes from the blood or diverts them to abnormal sites. It is not clear whether the delay in the recipients' tissues requires an active response to con A but, if so, then it does not proceed to blastic transformation.


Self-conscious behavior of infants: a videotape study.

The reactions of 4 infants each at ages 10, 15, and 20 months were recorded on videotape as they responded to their own simultaneous video image, their own previously taped video image, the image of a control infant, and that of a female stranger. The subjects' responses were coded by 2 research assistants, ignorant of the original stimuli and the purpose of the study. The following behavioral categories were used: attends, sociable behavior, curiosity, unhappiness-withdrawal, and self-consciousness. The 1st-step discriminant according to a matrix algebra analysis between age groups was self-conscious behavior in response to the simultaneous video image. Twenty month-old infants were significantly different in their display of self-consciousness from the 10 and 15 month-old groups; the latter did not differ from each other.


Ontogeny of behavior in two inbred lines of selected mice.

The development over 11 ages of 14 reflex responses, 26 behavioral components, jumpiness, and left-right discrimination learning was studied in 2 strains of mice genetically selected for high (SRH) and low (SRL) rearing response frequency. Significant age-dependent differences between the strains were found mainly, but not exclusively, in the behavioral components, e.g., rearing, jumping, scratching, defecating. Two-week-old pups of both strains showed good acquisition and retention in learning tests without shock, but the "jumpy" behavior disturbed performance to a certain degree in the SRH strain. Although less active initially, SRH mice were ahead at later developmental stages. Whether these differences are determined by the gene controlling rearing frequency or by other genes remains undecided.


Effect of arousal conditions during reinstatement treatment upon learned fear in young rats.

The role of shock and epinephrine-induced arousal in the reinstatement of learned fear was investigated in young rats. Groups of 21-day-old rats received classical fear conditioning to the black compartment of a black/white avoidance box. One week later each rat received one of a number of reinstatement conditions consisting of exposure to the apparatus cues, non-contingent foot shock, or exogenous epinephrine injections, alone or in combination. Subjects were tested for retention of spatial avoidance behavior 1 week following reinstatement. Reinstatement with epinephrine and exposure to the training contextual cues, non-contingent foot shock followed by cue exposure, and non-contingent foot shock alone were all found to be as effective as shock administered in conjunction with the cues (the same conditions as those prevailing during training). Cue exposure alone and epinephrine injections without the training cues were ineffective reinstating agents.


The role of auditory stimulation in responsiveness in young chicks.

The mechanism of action of the auditory signal in increasing responsiveness to a visual-auditory stimulus in chicks of 14-48 hr was examined. Stimulus effectiveness of an auditory signal dissociated from the visual stimulus was less than proximate auditory signal presentation but greater than a silent visual stimulus. Familiarity with the auditory signal increased and decreased responding under proximate and dissociated presentation, respectively. These data were interpreted as confirming the influence of auditory stimulation via increased arousal, and as indicating the possibility of selective responding to specific features of the auditory stimulus when its localization at the visual stimulus is possible.


Exploration and play with objects in domestic kittens.

The responses of 12 kittens to unfamiliar and familiar objects was tested. Four categories of behavior were measured: exploration, play-exploration, play, and non-manipulatory contact. The results indicated that exploration and play-exploration were used for longer durations with unfamiliar objects and play was used for longer durations with familiar objects. Rank-order correlations between the measures showed that objects explored were not correlated with objects played with or play-explored. Analyses of the rankings revealed that small size and mobility were important object properties of play. The results suggest that exploration involves learning about stimulus properties, play-exploration involves learning about perceptual-motor properties, and play involves learning to coordinate movements with those of moving objects.


Increase of the corticosterone level in ducklings during the sensitive period of the following response.

Increased fear may be one of the factors limiting the sensitive imprinting period. Thus, we analyzed corticosterone levels in 121 Peking ducklings during and after this sensitive period using the method of competitive protein binding. The data pointed to a corticosterone increase within a period of 12-28 hr after hatching as well as to the presence of a circadian rythm. The low coefficient of determination of post-hatch age and corticosterone level (8%) pleads for a multi-dimensional system. However, the corticosterone increase may be the basis for an increase in fear and a decrease in the likelihood of imprinting.


Development of learning and memory in mice genetically selected for differences in brain weight.

Mice selected for high (H), medium (M), and low (L) brain weight were trained to the goal arm opposite their preference in a shock-escape T-maze at 7, 9, 11, or 13 days of age. Twenty-four hours later, half of the trained groups at each age received additional training to the original goal, whereas the other half was trained to the opposite goal. Maturational control groups without prior training were trained on the selected retest days for the previously trained groups. Improvement in correct choice-point turns during training was suggested for the H-line by 9 days of age and by 11 days of age for the M- and L-lines. During retraining, H-line mice demonstrated 24-hr retention effects by 10 days of age, whereas 24-hr memory was not indicated for M- and L-lines at any of the ages investigated. These results indicate that the onsets of learning and memory were influenced by genes affecting brain weight, in that H-line mice demonstrated more rapid brain growth as well as heavier brain weights at every age studied as compared with M- and L-line mice which showed similar brain growth functions.


Actions of atmospheric ionization on spontaneous activity of an amphibian larva.

In Pleurodeles waltlii (Urodela) larvae, spontaneous activity and the tendency to leave water are significantly influenced by artificial air ionization. Atmospheric ions of negative and positive polarities have opposite effects: the latter reduce spontaneous activity by 48% whereas negative ions increase it by 39%. This difference must be considered the result of a specific behavioral effect rather than attributable to the stage of development of the larvae. A comparison of our results with data in the literature indicates that the action of the air ions on amphibian activity may involve the modulation of serotonin and prolactin releases.


Effects of stimulus intensity and stimulus duration during acoustic priming on audiogenic seizures in C57BL/6J mice.

The effects of stimulus intensity and stimulus duration were examined in C57BL/6J mice not susceptible to audiogenic seizures (AGS) on the 1st exposure to an acoustic stimulus. Two experiments were performed. In the 1st, 16-day-old mice were exposed to 108, 112, 120, or 127 dB for 60 sec. Mice were then tested for susceptibility to AGS at varying ages thereafter. Increasing intensity of noise during priming resulted in heightened peak seizure risk, and extended duration of peak seizure risk, and a prolonged time of seizure risk. In the 2nd experiment, mice were exposed for 5, 15, 30, or 60 sec to 127 dB of noise. Five seconds of noise was barely sufficient to induce later susceptibility to AGS. Increasing stimulus duration from 15 to 30 to 60 sec resulted in increasing seizure risk and duration of peak risk period.


Effects of thyroxine on infant development of undernourished rats.

The rehabilitative effects of exogenous thyroxine on infant development of undernourished animals were examined. Thyroxine injection accelerated the rate of body growth, age at eye opening, tooth eruption, and several emitted behaviors in undernourished infant animals. The data indirectly support previous findings that undernutrition induces hypothyroidism and that exogenous thyroxine might be an effective rehabilitative agent.


Non-accidental injury: a two-year study in central Liverpool.

In the two years following the implementation in Liverpool of a case conference system for dealing with non-accidental injury to children, 76 children were discussed at 73 such conferences. Factors in both the children and their families were identified as predisposing to non-accidental injury, notably male sex, illegitimacy, low birthweight, previous injuries in the children, the mothers having become pregnant at an early age, and the families having environmental stress factors. The evolving rôle of the case conference system in providing support for affected families is discussed.


Clinical application of evoked electroencephalographic responses in newborn infants. I: Perinatal asphyxia.

Evoked electroencephalographic responses are useful for the study of cerebral maturation in full-term and pre-term newborn infants. In an attempt to achieve wider clinical application, 57 newborn infants with differing degrees of perinatal asphyxia were examined. Altogether 154 examinations were performed. In all of them photostimulation was used, and in 72 investigations somatosensory evoked responses were also recorded. The following results were obtained: (1) Visual evoked responses were affected in 85 per cent of the cases. Somatosensory evoked responses were affected less often - in 65 per cent of the newborn babies examined. The incidence and degree of deviations were related to the degree of asphyxia. (2) The most characteristic features of the evoked responses in asphyxiated infants were abnormal response patterns, increase of latency and poor photic driving. (3) On the basis of all alterations observed, a scoring system was developed which enabled quantitative evaluation. The evoked response risk-score correlated well with the degree of asphyxia. (4) Repeated observations were important: a permanently high risk-score at repeated investigations was a serious prognostic sign.


Non-operative treatment of scoliosis in cerebral palsy: preliminary report on the use of a plastic jacket.

The use of a removable orthoplast jacket to treat scoliosis in 48 patients with cerebral palsy is described. Because of the short follow-up period - nine to 60 months - this paper reports preliminary findings only, but it is felt that the feasibility of conservative treatment of scoliosis in such patients has been demonstrated by the low incidence of complications and patient rejection, and its effectiveness has been shown by halting the progression of curvature in 38 of 41 patients followed for an average of 26 months.


Sensory nerve conduction in the spinal muscular atrophies.

Sensory conduction velocities were determined in the sural or median nerve in 16 patients with spinal muscular atrophy of the severe (Werdnig-Hoffmann), intermediate, or mild (Kugelberg-Welander) forms. In all cases there were normal sensory conduction velocities  in one of the nerves tested, although sural nerve responses were not obtained in the four youngest patients.


Bizarre posture and movement disorder with third ventricle astrocytoma.

An eight-year-old girl presented with a bizarre posture and gait and was diagnosed as having hysterical astasia-abasia. She walked with marked lordosis and head hyper-extended, and would walk backwards across the room to a bed or chair for support. She had a midline astrocytoma and the disorder was relieved with removal of the tumour. The unusual symptomatology accompanying many midline lesions is re-emphasized.


Smith-Lemli-Opitz syndrome: neuropathological and ophthalmological observations.

The case of a three-year-old boy with the Smith-Lemli-Opitz syndrome is reported. In addition to the constellation of skeletal and genital anomalies classically described in this syndrome, this patient had spontaneous opsoclonus-like eye movements, strabismus, lack of visual following responses and of opticokinetic reflexes. At autopsy the cerebellar vermis was found to be absent. There were retinal hemangiomas. Microscopical examinations showed loss of Purkinje cells and extensive neuronal degeneration within dentate nuclei, associated with patchy demyelination of cerebellar peduncles and central white matter. These findings may contribute to the explanation of the pathophysiology of opsoclonus and some of the neuro-ophthalmological findings.


Congenital hypocupraemia syndrome with and without steely hair: report of two Japanese infants.

Two Japanese infants with Menke's kinky hair syndrome are reported. The unusual finding in one infant was the absence of the hair abnormality characteristic of this disease; other findings were consistent with the diagnosis. It is suggested that hair abnormality cannot be relied upon for the diagnosis and that the term "kinky hair" is anappropriate. In its place "congenital hypocupraemia" is proposed as the diagnostic term to embrace patients with and without hair abnormality. Serum copper determination is a simple and reliable test in the diagnosis of this syndrome and should be done routinely in all male patients with unexpected deterioration. The angiographic features present in these patients with unexpected deterioration. The angiographic features present in these patients are characteristic but not pathognomonic of the disease. Subdural hygroma, a common finding, is the result of severe brain atrophy and little can be expected by surgical intervention.


The expression enzyme activity of biopsy tissue from the small intestine.

In a study to determine the most suitable method of expressing activity of jejunal mucosal enzymes, the effect of variation of thickness and protein concentration of biopsies was assessed. Despite wide variation of both these factors, we found no advantage in expressing enzyme activity by reference to either surface area or protein content. Expression of activity by reference to weight of biopsy gave the lowest variance for each of the enzymes studied and, since it is also the easiest measurement to make, it would appear to be the preferred means of expressing jejunal mucosal enzyme activity.


Functional and structural characteristics of the jejunum and ileum in the dog and the rat.

The dog jejunum is a much denser tissue than the ileum, with a greater weight per unit length and higher proportion of mucosal tissue. Morphometric analysis reveals longer and wider villi, deeper crypts and larger enterocytes in the jejunal mucosa. Uptake of phenylalanine or beta-methyl-glucoside by tissue slices in vitro is slightly greater in jejunal than in ileal tissue. The levels of acid phosphatase and alkaline phosphatase in the individual enterocytes are significantly greater in the jejunum, according to quantitative histochemical analysis. The absorption of water, sodium, potassium, chloride and glucose in vivo is significantly smaller in the jejunal than in ileal loops, particularly when expressed in terms of unit mucosal weight. Sodium and water absorptions are stimulated by glucose at both sites, but the stimulation is significantly greater in the ileum. Opposite results have been obtained in rats where the transport of phenylalannie in vitro is greater in the ileum, but water, electrolyte and glucose absorption in vivo is greater in the jejunum.


Massive pancreatic ascites without carcinoma. Report of three cases.

Three cases of benign pancreatic ascites have been added to 94 cases reviewed from the literature. Common characteristic of this syndrome were chronic alcoholism, intermittent abdominal pain, nausea, vomiting and considerable weight loss which occurred despite fluid accumulation. Markedly elevated protein and amylase levels in the ascitic fluid, hyperamylasemia and hypoalbuminemia were the major diagnostic clues as to the pancreatic origin of ascites. Predominant pathological findings were chronic pancreatitis with or without pseudocysts, pancreatic duct disruption, lesion which were considered to be the major pathogenic factor besides lymphatic obstruction by leaking pancreatic juice into the peritoneal cavity. Early laparotomy for diagnosis and treatment is essential. ERP might be of great value in diagnosis.


The effect of cholecystokinin on human taenia coli.

Superfusion of twelve human Taenia Coli strips with cholecystokinin (CCK) (boots and GIH Karolinska), CCK-octapeptide and glucagon at doses of 25--1,000 mIDu/ml evoked muscular contractions. Dose-dependent response to acetylcholine (ACH) (0.15--1.0 mug/ml) was not altered by an underlying contraction induced by CCK, CCK-octapeptide or glucagon. Though atropine (0.1 mug/ml) abolished ACH effects, hormonal responses were unaffected. The muscles' sensitivity was highest of CCK (Boots) and lowest to CCK-octapeptide, and the sigmoid colon was more sensitive than other parts of the bowel to both. Addition of glucagon had no effect on CCK-induced (Boots) responses. The results suggest (1) CCK and CCK-octapeptide act directly on the Taenia coli; (2) biologically active impurities in the whole CCK preparations explain their apparent increased activity; (3) glucagon does not block ACH or CCK, nor inhibit, directly, muscle contractions; (4) atropine (0.1) mug/ml)) does not interfere with CCK or CCK-octapeptide on colonic muscle.


Why tuberculosis is still a health problem in the aged.

Modern chemotherapy has made the treatment of tuberculosis effective and simple. What is required is a high index of suspicion for the disease, particularly in the older members of the population. When tuberculosis is suspected, a skin test should be performed and sputum examined for acid-fast bacilli. If the skin test is positive and the x-ray compatible, therapy with isoniazid and ethambutol should be initiated while evaluation of the patient continues. Therapy need not be complicated, and the patient can be returned to his usual environment promptly if a few simple rules are followed.


Life-threatening infections: how to choose the right antibiotics.

Pneumococcal pneumonia in two or more lobes in frail, elderly patients; staphylococcal and Gram-negative rod pneumonia in patients of any age; lung abscesses; septicemia; endocarditis; peritonitis; and meningitis are life-threatening infections. To save patients with these infections, the physician should know the causative organism and educate himself by cultures; estimate the whole body bacterial burden and decrease bacterial numbers by incision and drainage where large collections of pus are accessible; choose antibiotics with care and use two antibiotics if serious prognostic signs are present initially, if there is a change for the worse, or if the laboratory report indicates that multiple organisms are present; check the serum bactericidal level and repeat this test if the route of antibiotic administration is changed; watch for and treat underlying disease; and always monitor for septic shock. Aged patients need special care, as they often have severe underlying disease. The bacterial burden is often high before infection is recognized in elderly patients, and age itself interferes with host defenses.


Cephalexin: clinical effectiveness in geriatric patients.

A clinical and bacteriologic study was done in 298 elderly patients who had infections that were treated with cephalexin. Satisfactory clinical responses occurred in 93% of the 44 patients with respiratory tract infections, 96% of the 27 patients with skin and soft tissue infections, and 87% of the 227 patients with urinary tract infections (15 had asymptomatic bacteriurial); bacteriologic responses were satisfacoty in 80, 74, and 72 percent, respectively. The clinical response to cephalexin treatment was the same in 283 patients over age 65 as in 902 patients 16 to 64 years of age. Only 7% of 934 elderly patients had adverse reactions, which were generally mild. The BUN, SGOT, and hematopoietic values showed no change. Thus, cephalexin can be recommended for the oral treatment of many common infections in the elderly.


Can fracture of the femoral neck be predicted?

Hip radiograms made 15 to 25 years previously in 39 women were examined. These women were between 58 and 62 years old when the first radiogram was made, and all sustained cervical or trochanteric fracture of the upper end of the femur on an average of 14 years later. The trabecular pattern of the upper end of the femur was classifed according to Singh, and the medial cortex of the femoral neck was measured and expressed as a fraction of the total width (femoral neck index). For comparison, the same information was collected from a control sample of films taken during the same period in women who did not sustain subsequent hip fracture. The cortex was thinner in women who later had hip fracture than in control women. Women with coxarthrosis had the highest cortical ratio. The trabecular pattern in women who later had hip fracture shifted in the direction of osteoporosis in comparison with the controls. It was not possible to predict from either measurement which hip would fracture or when fracture would occur. This study demonstrates that by using only simple measurements on hip radiograms, it might be possible to include in a sample of women selected for a therapeutic trial those who are likely to sustain hip fracture.


Stroke: incidence and risk factors.

The incidence of stroke was estimated prospectively in a total population of 2,502 persons over age 65 who resided in homes for the aged. The incidence in persons born in Asian and African countries was close to that in persons born in European countries. No sex differential was found in either ethnic group, and there was no significant increase in the incidence of stroke with advancing age in either sex. In the European population, prior heart disease was the strongest risk-increasing factor, ranking ahead of hypertension. Diabetes mellitus was not associated with a higher risk of stroke among the women; the findings for the men were inconclusive. In the Afro-Asian population, the risk of stroke was related to heart disease and diabetes mellitus but was not associated with blood pressure. Total serum cholesterol or relative weight was not associated with stroke in either group. The early establishment of programs for the control of hypertension and stroke appears most desirable.


[Phenylalanine metabolites in the urine after oral phenylalanine loading. Significance for the discrimination between classical phenylketonuria and variations of hyperphenylalaninemia (heterozygotes and homozygotes)].

Modern newborn mass screening for inborn errors of metabolism results in detection of newborns with hyperphenylalaninemia. This investigation demonstrates that gaschromatographic analysis of phenylalanine metabolites in urine after phenylalanine challenge is a useful method for discriminating between classical phenylketonuria and hyperphenylalaninemic variants.


[Autologous ureter transplantation. Results of animal experiments].

Autologous transplantation of the ureter in the whole lengths was carried out successfully. After unilateral nephrectomy the ureter was cut from the bladder, denudated and wrapped in the omentum majus. 4 weeks after that operation revascularisation of the ureter was pronounced so that the ureter could be used for reanastomosis with the renal pelvis and the bladder on the contralateral side. One dog lived with the transplanted ureter for one year and then died during birth of 5 puppies. One dog is living now since two years and is healthy.


[Practical exercises in surgical technics in the traumatological laboratory].

The surgical training in the traumatological laboratory at the Surgical University Hospital in Munich has proven to be quite successful. The laboratory offers the young resident an opportunity to become familiar with the latest surgical methods within the fields of reconstructive and traumatological surgery. The so achieved knowledge will then be extended in the courses for osteosynthesis in which he will later participate. The laboratory also offers the possibility for experimental research as well as clinical followups and statistical documentation.


[Clinical findings in porphyria cutanea tarda].

Disturbances in the iron metabolism can quite frequently be observed in patients with porphyria cutanea tarda. Studies on 10 patients with porphyria cutanea tarda indicate that elevated iron levels are correlated with decreased latent and normal total iron binding capacity in the serum. Morphological examinations of the liver showed alterations as can be found in fatty liver up to cirrhosis, which -- in most instances -- were associated with iron deposits in the hepatocytes.


[Prevention of postoperative thromboembolic complications with subcutaneously administered small doses of heparin].

In a prospective study 3 x 5000 IU sodium heparin s.c. have been used for the prevention of postoperative deep vein thrombosis. Prevention started preoperatively in general surgical and urological patients. The diagnosis was made in all cases by means of the iodine 125fibrinogen test. In 2 out of 22 patients with a correct protocol deep vein thrombosis was diagnosed. 4 patients showed bleeding complications, in 2 of them heparin had to be stopped. A review of the world literature reveals that heparin prevention has been tested in general surgery in 2253 patients. The incidence of deep vein thrombosis was 8.6% compared to 28% in the controls. In orthopedic surgery only 279 patients are documented, the deep vein thrombosis frequency dropped from 46% to 22.2%. The results are contradictory. Both in urology and gynecology only few patients have been studied, definite conclusions are therefore not possible. The number of fatal pulmonary emboli in about 4000 patients under heparin prevention was 0.2%, in a control group of similar size 0.8%. This difference is statistically significant.


[Diagnosis of the placental function with special reference to the pregnancy-specific protein SP-1].

Following a description of the three different functions of the placenta (respiratory, nutritive, endocrine) and their failures the most common function tests are presented. Special emphasis is put on the evaluation of a recently described pregnancy-specific protein (SP1) in the maternal serum. The amount of the substance produced by the placenta correlates well with the fetal weight and well-being in cases of EPH-gestosis and idiopathic placental insufficiency; correlation was not as well in mild EPH-gestosis, diabetes and RH-incompatibility. The validity of measuring SP1-production seems to be similar to that of HPL. The method of quantitative determination is simple and possible even in a smaller hospital.


[Fibrinolytic therapy in deep venous thrombosis of the upper and lower extremity].

Fibrinolytic therapy was carried out in 59 patients suffering from a total of 60 deep venous thromboses of the iliac segment (n = 24), the femoropopliteal segment (n = 18), the deep calf veins (n = 2), or the subclavian vein (n = 16). 46 patients received streptokinase (SK), 4 were given urokinase (UK), and 10 were treated with streptokinase followed by urokinase (SK + UK). The duration of fibrinolytic therapy was between 19 and 596 hours (x = 166 +/- 111 hrs). Phlebographic examination was used to determine the location of the thrombotic occlusion as well as to evaluate therapeutic results. To assure sufficient anticoagulatory protection during therapy with streptokinase the dose of streptokinase was either reduced by steps of 20,000 U/hr to a minimum of 40,000 U/hr or heparin was added as a continuous infusion. Urokinase was administered with a mean loading dose of 75,000 IU followed by an average maintenance dose of 40,000 IU/hr; it was always given in combination with heparin. When therapeutic success was graded as complete/partial/no recanalisation, the following results were obtained: thrombotic occlusion up to 1 week old 35%/48%/17%; up to 2 weeks old 57%/14%/29%; 3 or 4 weeks old 12%/38%/50%; older than 4 weeks 13%/37%/50%. The two most common side effects were a fall of the hemoglobin and a rise of body temperature. Treatment with SK had to be interrupted for bleeding in two cases. One patient diet after rupture of the liver and of the spleen following development of subcapsular hematoma in these organs, 3 patients survived pulmonary embolism without major long-term impairment. Considering medical and social aspects (preservation of capability for working in young adults) it appears justified to administer fibrinolytic agents up to a thrombus age of 14 days, in some cases even up to a thrombus age of 28 days. Good results in cases of deep vein thrombosis of the lower limbs are often obtained only when fibrinolytic therapy is extended beyond 96 hours. It should be performed in intensive care units only. Follow-up examinations of the venous drainage capacity up to 2 years after fibrinolytic therapy document the good therapeutic effect that is warrented by streptokinase or urokinase induced complete recanalisation.


[Comparative echoventriculographic studies in premature, low weight and mature infants].

In 135 preterm and low-weight prematures and in 17 low-weight infants with normal time of gestation the diameter of the body region (= Cella media region) of the lateral ventricles and the width of the third ventricle were measured by means of one-dimensional echoencephalography. The observations were made during the period of the first 30 months. The diameter of the parietal cerebral matter was defined as difference of the biparietal skull diameter minus width of the body region of both lateral ventricles. By comparing healthy, maturely born children with preterm children the fetal age was taken as a basis. Statistics were taken from the age of one month onward. The preterm children showed significant lower values for the diameter of the cerebral matter and the index of the body region. Accordingly the values for the width of the body region were higher. The results are explaned not only with atrophic changes. According to our investigations they also can be caused by a retarded maturation of brain, which can be compensated partly or completely in the course of the child's development.


[The etiology of transitory hyperbilirubinemia in newborn infants].

Recent investigations have shown that haemolysis plays a major role in the etiology of transitory hyperbilirubinaemia of the newborn. Our studies indicate that unconjugated bilirubin itself is in part the causative agent for this haemolysis. In vitro bilirubin causes damage of red cells which finally results in haemolysis. Newborns suffering from transitory hyperbilirubinaemia have a red cell population which is especially sensitive to the haemolytic effects of bilirubin. The initial bilirubin increase after birth is caused by relative dysfunction of the liver, causing further haemolysis of bilirubin sensitive red cells. Hyperbilirubinaemia decreases when all sensible red cells are destroyed and liver function improves.


[Pathogenesis of multiple sclerosis. Work-hypotheses and experimental data].

In spite of a history of more than 100 years, the pathoaetiology of multiple sclerosis is still unknown today. Research is based on three working hypotheses, i.e. on an immunopathological disease origin, on the conception that MS, as an infectious disease, is caused by a specific pathogen (slow virus infection) and on the assumption of a disturbance of basal metabolism or utilisation. The present position of the scientific foundation of the working hypotheses is presented in detail and supplemented by the results of our own investigations. Of particular interest are the geomedical studies which show that MS occurs more frequently in temperate climatic regions. In Europe, a latitude of 46 degrees forms a conspicuous boundary; in the USA this boundary is found at 38 degrees. North of this line there is a morbidity rate of 30 to 60 patients per 100 000 inhabitants, while south of it 15 cases at most per 100 000 inhibitants are found. Asia, especially in China and Japan, and tropical countries, where Multiple Sclerosis is practically unknown in the native populations, are exceptions. The observation that immigrants from areas with a low MS incidence into regions with a high risk of MS fall ill with the disease after years remains also unexplained. These peculiarities have given rise to the consideration whether there is a still unknown factor in the soil of high-risk areas or a specific pathogenic spectrum. In this connection, the question is also discussed whether the risk of MS in northern countries is associated with the excessive consumption of animal fat. The possible therapeutic and prophylactic significance of unsaturated fatty acids is emphasized. Our own results with the Schilling-test, determination of gastric acids, rubella titres in serum and cerebrospinal fluid, the immunofluorescence test of the serum and CSF, determination of tissue antigens (HLA) in families with multiple incidence of Multiple Sclerosis are discussed. On evaluation of a large series of patients, it is striking that Multiple Sclerosis and juvenile diabetes seem to be mutually exclusive (Schrader). Likewise, in MS statistics no other immunopathologic disease such as rheumatic diseases or bronchial asthma was found. Interestingly, also in 400 MS patients examined, hyperuricaemia or gout, which are widespread among the populace, were not found in a single case.


[Analysis of therapeutic success and of obstetrical results in sterile marriages].

In the course of sterility therapy 375 pregnancies were observed in 296 patients. 63 women conceived twice or more. At the first visite the mean age of the patients was 25,8 years, the mean duration of sterility 2,7 years. A primary sterility was observed in 207 and a secondary sterility in 98 cases. The main therapeutic procedure was the induction of ovulation with FSH/LH releasing preparations (Clomiphen, Cyclofenil, Epimestrol) (40,3%), followed by the substitution therapy with human gonadotrophins (22,7%). 78 pregnancies ended by spontaneous and 4 by artificially induced abortion. The abortion rate in this study was 20,8 %, exceeding considerably the normal abortion rate. The rate of extrauterine pregnancies was also increased, being 2,4%. There was no significant difference in the abortion rate of pregnancies with or without induction of ovulation. The age at the time of conception and the duration of therapy had no significant influence on the rate of abortions. In 293 pregnancies the duration of gestation exceeded the 28th week. However, 33,1% of these pregnancies had complications that required hospitalisation. Almost 50% of the complications consisted of threatened abortion. The mean duration of gestation was reduced by 5 days, caused by a relatively high frequency of early births (16,9%). The mode of delivery of our patients was in 68,8% spontaneous delivery, in 16,2% caesarian section, in 15,0% forceps or vacuum extractions. This corresponds to the general mode of delivery of our hospital. Only after gonadotrophin therapy a higher caesarian section rate of 26,8% was noted. Out of the 310 live born children, 9,2% had a weight below 2500 g, owing to a multiple pregnancy rate of 4,1%. 4% of the children showed the signs of dystrophia. The perinatal mortality amounted to 5,1%. However, when the gonadotrophin induced multiple pregnancies are excluded, the rate is 2,7%. Only 2 cases of malformations were observed.


[HL-A polymorphism and its relation to cervix neoplasms].

Twenty-three HLA antigens were investigated in 121 patients with clinical cancer as well as 188 male and 212 female controls. Patients with cervical carcinoma showed significant differences in some HLA frequencies from that of controls. Patients with cervical carcinoma showed significant differences in some HLA frequencies from that of controls. In the localized form of the neophasia HLA-A3 was decreased, HLA-A9 and B 12 were increased. In the disseminated form of cervical carcinoma HLA-A 1 were found decreased and AW 32 and B 12 increased. HLA antigens could be factors, together with others yet unknown, i.e. immune response genes, HSV-2-infection, which produce an increased susceptibility to the disease.


[Significance of Australia antigen in the differential diagnosis and prognosis of hepatitis].

The Australia-antigen (HBSAG) is a simple detectable marker of an infection with hepatitis B virus. By demonstration of HBSAG an acute hepatitis B can be differentiated from other forms. Likewise the detection of HBSAG in chronic active hepatitis can differentiate the viral induced type from the autoimmune type. HBSAG is important with respect to the prognosis of an acute hepatitis B, because persistence for some months points at a transition to chronic hepatitis.


[Pulmonary emphysema. Changes in the pulmonary function of experimentally induced emphysema].

By intratracheal injection of the protease papain to experimental animals parenchymal changes in the lung can be induced, that resemble human emphysema. Papain (dosage 26 to 112 mg, 1 to 4 injections) was given intratracheally to 8 bastard dogs (weighing from 12.5 to 20 kg) during light general anesthesia. Pulmonary function was assessed in weekly intervals and related to morphologic changes in the lung. Static compliance of the lung and FRC measured during respiratory arrest were increased after papain, bronchial resistance, measured while artifically ventilated at constant pressure was also increased. Changes of static lung compliance and FRC were seen after the first administration of papain, but further increased with time of observation and after multiple doses of papain. Increase of resistance was not found before 5 weeks. At quiet breathing resistance was not increased at all. No significant changes were found of arterial pO2 and pCO2, pH, standard and actual bicarbonate, diffusion capacity for O2, tidal volume, minute ventilation and ventilatory rate. Morphological findings confirmed the changes described by others. Pulmonary function appears to be pathological at a time when morphology still seems to be normal. The question is discussed to what extent the model of experimental emphysema induced by proteolytic enzymes can contribute to the understanding of human pulmonary emphysema. Lung function in the course of experimental emphysema is compared with function in different clinical types of emphysema.


[Morbidity and mortality of widowed persons].

According to the literature, widowed persons show in comparison to married persons higher rates for mortality (especially due to cardiac diseases), for suicidality and for psychiatric morbidity. Potential sources of error appear to be unimportant. Younger widowed persons are at greater relative risk than older. Widowers react more immediately to the bereavement than widows.


[Diagnosis and therapy of lactose malabsorption].

Examinations of faeces (pH, Clinitest and Clinistix) are liable to contribute to the diagnosis of lactose malabsorption. To confirm the diagnosis the test is to be repeated while Lactase 500 is added to the child's milk. The enzyme does not split the lactase into the two monosaccharides, thus eliminating the malabsorption. The new drug Lactase 500 was used as a diagnostic parameter and for the treatment of lactose malabsorption in 20 infants. The effect on both groups was confirmed as mentioned by foreign authors. In addition to a very simple diagnostic method, which can be performed in the practitioner's office, there are two methods of treating lactose malabsorption: 1. feeding milk free of lactose, 2. feeding milk with an addition of Lactase 500. As in an earlier publication we assumed that about 10 per cent of the population suffers from secondary malabsorption of lactose, it seems advisable to check with the help of the described to simple methods all children with chronic diarrhoea.


Human adipose tissue in culture. VII. The long-term effect on growth hormone.

Biopsies of human adipose tissue were cultured for one week in vitro with or without different concentrations of human growth hormone (GH). After preincubation they were incubated in vitro for 2 hours analogous to the technique generally used for short-term experiments. The release of glycerol and incorporation of glucose into triglycerides were measured under basal conditions as well as in the presence of insulin or noradrenaline. An impairment in the basal glucose incorporation rate was found after the culture period with GH, but there was no concomitant effect on lipolysis. The effect of insulin on glucose incorporation was stimulating to the same extent as in the controls but the metabolis rate was even in the presence of insulin still below that of the controls. The effects of noradrenaline and of insulin on lipolysis were similar to those in the control group. It is concluded from the present study that a direct "diabetogenic" effect of GH on human adipose tissue can be detected. This effect developed successively over the seven days that the incubations were performed. It was due to a diminished basal rate of glucose incorporation and not to a direct resistance to the action of insulin and it was not related to increased lipolysis.


Alteration of plasma glucagon response to arginine after treatment in patients with diabetes mellitus, cushing's syndrome and hypothyroidism.

Effect of successful treatment on plasma glucagon response to arginine was studied in patients with diabetes mellitus, Cushing's syndrome and hypothyroidism. Exaggerated response of plasma glucagon to arginine infusion in diabetic subjects was normalized in those successfully treated with sulfonylureas and significantly improved in those treated with insulin. Patients with Cushing's syndrome and hypothyroidism also exhibited excessive responsiveness of plasma glucagon, which were completely normalized following treatment. The results suggest that the metabolic derangement is a main etiologic factor in inducing hyperresponsiveness of plasma glucagon to arginine in these disorders.


Increased glomerular filtration rate and glomerulopressin activity in diabetic dogs.

Studies of the chemical characteristics of glomerulopressin were carried out, and the results suggest that glomerulopressin is a glucuronic acid conjugate. Glomerulopressin activity, glucuronide concentration and glomerular filtration rate (GFR), plasma volume (PV), extracellular volume (ECV) and estimated hepatic plasma flow (EHPF), were measured in normal dogs, infused with saline or glucose and in pancreatectomized dogs infused with saline. Glomerulopressin activity, glucuronide concentration and GFR were also measured in pancreatectomized dogs infused with insulin (150 muU/min/kg) through the portal or femoral vein. The glomerulopressin activity, glucuronide concentration and GFR in glucose-infused normal dogs were similar to those observed in saline-infused animals, while they were greatly increased in pancreatectomized dogs. There was no difference between these three groups in PV, ECV, or EHPF. The infusion of insulin through the portal vein of pancreatectomized dogs reduced glomerulopressin, glucuronides and GFR to the values observed in normal dogs, while the infusion on insulin through the femoral vein did not decrease these levels. The increased glomerulopressin produced by pancreatectomy seems to be due to the lack of insulin reaching the liver. The results suggest that pancreatectomy induced an increase of glomerulopressin activity and that this humoral factor increases GFR.


Effect of prolonged glucose infusion on total serum fatty acids and free fatty acids in the rat.

This investigation evaluates the effect of prolonged glucose infusion on triglycerides and the composition in total serum fatty acids and free fatty acids in the rat. Glucose infusion over a period of 4 days leads to the following changes: serum triglyceride concentrations are two to three times elevated and serum insulin levels rise 10 times after 12 hours, followed by a steady decrease. Chain elongation is depressed in serum free fatty acids and even more in total serum fatty acids. In serum free fatty acids monodesaturation is unaltered whereas it is highly stimulated in total serum fatty acids. These alterations correlate with the changes of hepatic total fatty acids and do not correlate with changes of fatty acids from epididymal fat pads. The alterations reflect a specific carbohydrate-induced effect on hepatic fatty acid desaturation and chain elongation. They do not support the idea that serum free fatty acids are mainly secreted from the storage pool of adipose tissue; yet, they may have been newly synthesized in fat cells or even in the liver.


Effects of acetoxyprogesterone upon glycosaminoglycans in the uterus and salivary glands of rats.

The isolation and characterization of glycosaminoglycans was performed in uterus and submaxillary glands of castrated female rats receiving daily doses of 20 or 200 mug of acetoxyprogesterone and 100 or 1000 mug of progesterone. Chromatographic separation of glycosaminoglycans was performed on cellulose microcolumns. The uronic acid concentration in the uterus was decreased by acetoxyprogesterone, in every chromatographic fraction, but not by progesterone. The uronic acid concentration in the submaxillary glands was decreased by acetoxyprogesterone in fractions 1 (glycoporteins) and 2 (hyaluronic acid) and by progesterone in fractions 1 (glycoproteins), 2 (hyaluronic acid) and 7 (heparin);


Lipogenesis by hepatocytes of rats with hypothalamic obesity.

Hepatocytes were prepared from livers of rats with bilateral lesions of the ventromedial hypothalamic nucleus (VMN lesioned) and sham-operated control rats. The incorporation of tritium labeled water and 14C glucose and lactate into lipids was studied. Endogenous tritium incorporation into fatty acids in controls ranged from 7-20 muatoms 3H per 100 mg liver protein per hour, and in cells from VMN lesioned rats 25 to 80 muatoms per 100 mg/hour. In both types of cells addition of glucose had no effect on tritium incorporation, but the addition of lactate, pyruvate or alanine stimulated it 30-60%. There was little difference in the labeling of glycerol by the two groups. In cells from fasted refed control or lesioned rats, tritium incorporation was greatly increased and was equal in both groups. Incorporation of glucose carbon in VMN lesioned rats was three to ten times that of controls, but the contribution of glucose carbon to fatty acid synthesis was small.


Influence of contraceptive steroids on the turnover of plasma free arachidonic and oleic acids.

The turnover of plasma free oleic and arachidonic acids was determined in five healthy women before and after 3 months contraceptive treatment with a daily dose of 0.05 mg ethinyl estradiol and 0.25 mg d-norgestrel administered in a cyclic manner. The contraceptive steroids did not significantly influence the total plasma free fatty acid (FFA) concentration or the turnover of oleic acid. However, during hormone administration the fractional turnover of arachidonic acid increased by 40 per cent and its arterial concentration fell by 20 per cent. The portion of saturated fatty acids in the FFA fraction decreased during the contraceptive treatment. It is concluded that the treatment with contraceptive steroids (1) had no effect on the turnover of the main part of the FFA fraction, (2) increased the transport of the polyunsaturated arachidonic acid through the plasma pool, possibly as an effect of the estrogen component, and (3) stimulated the desaturation of saturated fatty acids to monoenes.


Role of endogenous calcitonin in the secretion of gastrin and gastric acid in rats.

Following pyloric ligation, serum immunoreactive gastrin levels and gastric acid accumulation in acutely thyroidectomized rats with autotransplanted parathyroid glands were significantly higher than those in thyroid intact rats. Furthermore, serum immunoreactive gastrin levels were higher in the absence than in the presence of the thyroid gland following the oral administration of glycine or rat chaw. These results suggest that endogeneous calcitonin has an inhibitory action on gastric acid secretion probably through the inhibitory action on gastrin secretion in rats.


Mechanism of the stimulation of RNA synthesis in rat liver nuclei by silybin.

The influence of the flavonolignane derivatives silybin, silybinhemisuccinate  and silybindihemisuccinate on the RNA synthesis in isolated nuclei from rat livers was studied. A stimulatory effect of silybin on the incorporation of [3H]UTP into nuclear RNA was found and the dose dependence could be demonstrated. The results support former findings that silybin stimulates RNA synthesis in rat livers in vivo and in hepatocytes. Experiments with purified nucleoli indicated that mainly the rate of rRNA synthesis is increased. The mechanism of this stimulation was elucidated by experiments with isolated RNA polymerases. It could be demonstrated that polymerase B is not affected by the flavonolignane, but the activity of polymerase A is increased, due to higher V at constant Km values. Thus silybin is shown to be an enzyme-stimulating effector.


Heterogeneity and partial purification of  human erythrocyte membrane acetylcholinesterase.

Triton X-100 solubilised human erythrocyte acetylcholinesterase (E0), when subjected to chromatography on Sephadex G-200, showed one enzyme activity peak (Eg) and a number of protein peaks (Pg). The same sample could be separated into several subfractions of enzyme activity on DEAE-cellulose by gradient elution with increasing sodium chloride. When the gel filtered enzyme peak (Eg) alone was rechromatographed on an ion-exchange column under identical conditions, it showed only one enzyme peak. But when Eg in combination with protein peaks (Pg) without enzyme activity is rechromatographed as a physical mixture on a DEAE-cellulose column under the same conditions, the preparation  could again be resolved into at least two fractions with enzyme activity. 2) Disc electrophoresis of fractions from DEAE-cellulose chromatography separated multiple bands which differ significantly from those produced by electrophoresis of E0. This suggests that E0 had undergone some form of conformational modification during the ion-exchange chromatography. However, this modification of E0 was avoided, if it was subjected to Sephadex G-200 chromatography before the DEAE-cellulose step. 3) A three-step technique (fractionation on Sephadex G-200, DEAE-cellulose chromatography and electrofocusing) has been performed for the purification of erythrocyte acetylcholinesterase. An enzyme preparation of high purity with a specific activity of 81 U/mg of protein was obtained.


Studies of the ligand binding to cholera toxin, II. The hydrophilic moiety of sialoglycolipids.

The binding between cholera toxin or its B-protein subunit and various ganglioside-related oligosaccharides was studied by equilibrium displacement dialysis. At low concentrations of ligand, the  binding of monosialo-gangliotetraitol exceeded that of the parent ganglioside II3NeuAcGgOse4-Cer, the possible cell surface receptor for the toxin. The terminal galactose residue and an intact carboxyl group of the sialic acid moiety of monosialo-gangliotetraose were found to be necessary for strong binding to the toxin.


Multihormonal regulation of sex-dependent 17beta-hydroxysteroid dehydrogenase activity in rat kidney cytosol.

The sexually differentiated activity of rat kidney cytoplasmic 17beta-hydroxysteroid dehydrogenase is subject to multihormonal regulation. Gonadectomy as well as the treatment of intact male animals with estradiol removes the repressive influence of testicular androgens, thereby allowing the activity in the male animal to reach the higher female level. The maintenance of this sexually undifferentiated activity level is a function of the thyroid gland, the adrenals and of growth hormone (somatotropin) and prolactin. Removal of the thyroid or the adrenals from intact animals decreases the activity and eliminates the sexual difference. Following the substitution of hypophysectomized animals with different hypophyseal hormones or gonadotropin preparations, only growth hormone and prolactin are effective in causing an increase in the very low activity. Thus, the sexual differentiation of renal 17beta-hydroxysteroid dehydrogenase activity observed in intact rats is clearly the result of the repressive action of testicular androgens on a multi-hormonally controlled activity level.


The changes in aldolase isoenzyme pattern during development of the human kidney and small intestine--demonstrated in organ extracts and tissue sections.

Aldolases A, B and C were determined by immunotitration analysis in extracts of human kidney and small intestine and demonstrated immunohistochemically in tissue sections of the same organs at various stages of development. By both techniques a change of isoenzyme pattern during development of the kidney and the small intestine was observed, leading from the predominance of A-type towards the predominance of B-type aldolase. In the extracts of kidney and small intestine the specific activity of aldolase B--but not that of aldolase A--rises with age by about one order of magnitude.  The histochemical investigation showed that the developmental change in aldolase pattern in the organ extracts is caused by the differentiation of proximal tubulus cells in the kidney and the differentiation of epithelial cells in the small intestine. Within these cells an increase in the concentration of aldolase B and a decrease in that of aldolase A takes place during development. The possible physiological role of this cellular change in aldolase isoenzyme pattern is discussed. Aldolase C was found only in low concentrations in fetal organs. Only in the kidney, a specific localization within the proximal tubules could be demonstrated.


The dissociation of the phalloidin-actin complex.

Phalloidin reduces the critical concentration [G]c = Kc-1 for the depolymerisation of rabbit muscle actin. Adding 1 equivalent of toxin reduces the [G]c by a factor of 30; adding 2 equivalents reduces the [G]c by a factor of 90. The depolymerisation of actin was measured by the exchangeability of 45Ca and [14C]ADP in equilibrium dialysis. Half dissociation of both the metal ion and the nucleotide were found at the same concentration. From this value we calculate the critical concentration for actin [G]c=1.05 x 10(-6)M. The analogous value in presence of 1 equivalent of toxin is [G]'c=3.7 x 10(-8)M. The dissociation from actin for a labelled phallotoxin, [3H]demethylphalloin, was likewise studied by equilibrium dialysis. The apparent KD for this toxin, as well as for the natural toxin phalloidin, is 3.6 x 10(-8)M. The value is identical to that of [G]'c. This indicates that the dissociation of the toxin and the breakdown of the filaments together with a concomitant release of Ca and ADP are interdependent events.


Studies on plant bile pigments, II[1]. Chemical and photochemical oxygenation of a phytochrome Pr chromophore model pigment to purpurins.

The chemical and photochemical oxygenation of 2,3-dihydrooctaethyl-1,19(21,24H)-bilindione (1), as a model for the chromophores of both phytochrome Pr and phycocyanin, has been studied in neutral and alkaline solution, and in the presence of zinc ions. By comparison with octaethyl-1,19(21,24H)-bilindione (5), the influence of ring A hydrogenation on the reactivity of bilins has been assessed. In the dark, 1 is attacked selectively and rapidly at C-5 yielding "purpurins", while 5 reacts slowly, and is attacked predominantly at C-10. Photooxidation of 5 yields the tripyrrinic "purpurin" 7 only. Photoreactivity of 1 is considerably enhanced, yielding "purpurins" and "violins" rapidly. In spite of UV-vis  and mass spectroscopic similarities, the "purpurin" 7 differs from the "purpurins" 6a,b by the loss of ring A. The facile cleavage at the C-5 methine bridge and the spectroscopic properties of "purpurins" are discussed.


Being with madness: personality characteristics of three treatment staffs.

The personality characteristics of the nonprofessional staff of Soteria House, an innovative residential treatment program for schizophrenics, are assessed and compared with characteristics of representative staffs from two more traditional mental health programs for schizophrenics: a university psychiatric ward and a community-based program staffed by a specially trained group of state hospital aides. A battery of self-report personality questionnaires was used. Analysis of the data indicates an over-all similarity of personality profiles in the three groups. All groups demonstrated two sets of characteristics considered desirable for therapists of schizophrenics: the ego-strength qualities of self-assurance, emotional maturity, independence, and autonomy, and the affective qualities of warmth, sensitivity, and empathy. However, within a third set of characteristics, descriptive of cognitive-attitudinal qualities, the Soteria staff possessed significantly more intuition, introversion, flexibility, and tolerance of altered states of consciousness. The authors speculate that it is this last set of characteristics that allows the Soteria staff to function in the program's intensive, unstructured treatment environment.


Length of stay and behavior patterns of hospitalized schizophrenics.

A behavioral observation system, which consists of a series of objectively described behavior categories and an apparatus for recording the duration and frequency of ongoing behaviors in each category, was used to study the behavior on the ward of 21 long-term and 21 short-term matched hospitalized schizophrenics. Results of the study supported the major hypothesis that long-term hospitalized schizophrenics show more withdrawn and inappropriate behaviors and fewer social and appropriate behaviors than short-term hospitalized schizophrenics. Among the short-term patients, those hospitalized from four months to one year showed the most adaptive behaviors and the fewest inappropriate behaviors.


Role expectations and behaviors in a group home program.

Patients and staff participating in a group home program operated by the Veterans Administration Hospital in Topeka, Kansas, were interviewed to determine their perceptions of what constitutes acceptable behavior and how the groups functioned. The interviews indicated that the behaviors accepted by group members--their own norms--differed markedly from the norms set by staff. The only behavior highly valued by both staff and group members was helping with household tasks. Staff placed great emphasis on personal hygiene and on participation in a daily work activity and a weekly group social activity, while group members placed emphasis on controlling open expressions of hostility.


Sensory dysfunction in adult schizophrenia.

The authors describe the postural abnormalities and sensory-integration deficits of process schizophrenics, or those who have had problems since childhood and who gradually slip into psychosis. A treatment program consisting of a variety of activities designed to correct those deficits was conducted for one year at the University of California, Irvine, Medical Center; it was coordinated by the occupational therapy department. At discharge the six participants had improved, and their gains were maintained at one-year follow-up. The authors believe similar programs would be useful in board-and-care homes and long-term-care facilities.


Patterns of psychiatric consultation in a general hospital.

The authors conducted a study of the rate of utilization of psychiatric consultation by various services at two general hospitals. The study found that the rehabilitation and plastic surgery services had the highest ratio of consultations to admissions. Depression was the most frequent reason cited in staff requests for psychiatric consultation. Male patients were overrepresented among the consultees in proportion to their number in the total general hospital census. The authors conclude that appropriate psychiatric consultation can enable the majority of patients with psychiatric problems to be maintained on the wards to which they were admitted, and that psychiatric liaison staff should be trained in a variety of consulting roles.


Shifting tuberculosis care to the general hospital.

Control of tuberculosis infection within the hospital is of major importance to general hospitals that assume the responsibility for providing tuberculous patients with primary care services. Because patients vary in their potential infectiousness, each patient's disease should be assessed individually. Patients who have completed a prescribed course of treatment are not infectious, and no precautionary measures are indicated. Patients with positive sputum who are receiving chemotherapy are rarely infectious, but they should be lodged in a room with air control. Effective antituberculous chemotherapy and adequate ventilation of the environment are the most important means of achieving infection control. Each hospital should have an infection control committee that is responsible for implementing infection control policies and for ensuring that patients with tuberculosis receive high-quality medical care. Educating personnel about tuberculosis, providing necessary consultation services, and making sure that patients are referred properly at discharge are important functions of the committee. Only those hospitals that are willing to meet these minimum standards should assume this responsibility.


Concentric hemorrhagic necrosis of the myocardium. A morphological and clinical study.

Froty-nine cases of concentric hemorrhagic necrosis of the left ventricular myocardium were reviewed in a series of 97 autopsy studies in patients subjected to cardiopulmonary bypass for various types of cardiac surgery. The gross and microscopic findings were analyzed in order to define the morphologic evolution of the lesion. The extent of involvement was graded by gross examination of serial transverse sections of the heart. Microscopically there were five major histologic changes, probably representing the sequential evolution of the lesion, i.e., contraction bands, subendocardial hemorrhages, coagulative necrosis, healing by granulation tissue, and fibrosis.  The location of the lesion conincided with the vulnerable region of the microcirculation. Owing to the implementation of new surgical techniques, the cases were subdivided into two groups, one covering the period from 1963 to 1970 and the other , 1971 to 1974. Concentric hemorrhagic necrosis was less frequent in the more recent group, but when it was present it was more pronounced in the individual heart. The lesion in the earlier group was milder but demonstrated a higher incidence of platelet microthrombi in the heart. In the recent cases concentric hemorrhagic necrosis tended to be more diffuse in aortocoronary bypass than in valvular replacement surgery. We discuss one possible explanation for the development of this lesion, i.e., transient hypoxemia occurring at the time of cardiopulmonary bypass, followed by reperfusion and accelerated necrosis with hemorrhage.


Carotid body hypertrophy in patients with cystic fibrosis and cyanotic congenital heart disease.

The carotid bodies from 71 patients ranging in age from 28 weeks' gestation to 30 years were obtained at autopsy. Patients were divided into two groups based on the presence or absence of chronic hypoxemia. There was a high correlation between the weight of individual carotid bodies in each case. Among the 12 patients with chronic hypoxemia, eight patients had carotid bodies heavier than predicted by statistical analysis. Of these eight patients, six had cystic fibrosis and two had cyanotic heart disease. Morphometric and cell population analyses of the carotid bodies from these eight patients and from those of the control population indicated that enlargement of the carotid bodies during normal or abnormal growth results from proportionate increases in lobule parenchyma and stroma. There was also an increase in the width and length of the lobules without an increase in the diameter of the cell cords or a change in the size or proportion of the chief cells. Growth and development of the carotid bodies were studied in a control group of 59 patients without chronic hypoxemia. There were no sex related differences in carotid body weights. The combined weight of the carotid bodies correlated most strongly with body weight, although there was some correlation with age and body length. A regression equation reflecting the data relating to body weight (BW) is: Combined weight of carotid bodies (in mg.) = 0.29 BW (in kg.) +3.0. Leukemic infiltrates were present in two patients with acute lymphocytic leukemia, and diffuse lymphocytic infiltration with nodule formation was present in one patient with mental retardation. Metaplastic cartilage was present in a carotid body of one patient.


Thymus related tumors and tumor-like lesions in childhood with rapid clinical progression and death.

Tumor and tumor-like lesions of the thymus, excluding Hodgkin and nonHodgkin lymphomas, are among the least frequent mediastinal tumors in childhood. For this reason the diagnosis is often overlooked. The clinical and pathologic features of four thymus related masses, three of which were thymomas and one a thymic cyst, are reported in children between the ages of five and 15 years. The thymic cyst occurred in a child with a five year history of aplastic anemia. A rapid clinical course to death occurred in all four cases. The behavior of these lesions is compared  with that described in the literature. The impression exists that thymomas in the pediatric age group are much more aggressive than those in adults. There are also some signifant differences in their histopathologic appearance.


Cell proliferation in normal human breast ducts, fibroadenomas, and other ductal hyperplasias measured by nuclear labeling with tritiated thymidine. Effects of menstrual phase, age, and oral contraceptive hormones.

The proliferative rates of terminal duct cells were studied by tritiated thymidine labeling in vitro in 104 specimens of benign breast tissue from 92 women, The tritiated thymidine labeling index showed a cyclic pattern consistent with regulation by female sex hormones. It was low during the segment of the menstrual cycle encompassing days 2 through 15 (early cycle) and often was elevated during the segment encompassing days 16 through 1 (late cycle). The early cycle geometric mean index for morphologically normal terminal ducts was 0.19,and for ducts of fibroadenomas it was 0.77. The geomitric means for latecycle were 1.03 and 1.67 respectively. The difference for normal ducts between early and late cycles was highly significant (p less than 0.001). For  both normal ducts and fibroadenomas the tritiated thymidine labeling index correlated negatively with the age of the patient, and the higher index value of fibroadenoma ducts relative to normal ducts was entirely accounted for by the younger mean age of the fibroadenoma patients. Oral use of contraceptive hormones could not be shown to change the index in either normal ducts or fibroadenoma ducts. Based on a postulated duration of DNA synthesis of 12 hours, the mean turnover time of the cells of normal terminal ducts would be approximately 22 days for 20 year old women with regular menstrual cycles, and would increase to 147 day at age 40. The mean potential doubling times of fibroadenomas would be approximately 33 days. The index values of other benign ductal proliferative lesions of the breast were similar to those of fibroadenomas and normal terminal ducts.


Peritoneal mesothelioma.

The cytohistology in 82 cases diagnosed as malignant peritoneal mesothelioma was correlated with available clinical and gross pathologic information. The cases were then evaluated as to ceratainty of diagnosis. The material had come from a large number of sources, most of it having been traced by a history of occupational exposure to asbestos. A relatively short interval of significant symptoms, with already existent diffuse peritoneal involvement and ascites, and an average survival time of less than a year characterized the group. The microscopic morphology formed a spectrum from highly characteristic, pure epithelial and mixed epithelial and sarcomatoid types, through nonspecific although relatively differentiated appearances, to pleomorphic analplatic proliferations. Local invasion and metastasis were common but much more limited than with tumors of other histogenesis showing comparable serous membrane involvement. Autopsy was of considerable exclusionary value although not in itself always determinative, and mucopolysaccharide histochemistry was occasionally decisive in diagnosis. Because of the microscopic versatlity of mesothelioma and the clinical and gross morphologic overlap with other neoplasms, all available data must be taken into consideration in arriving at a diagnosis. We believe that the dgree of certainty of diagnosis should be indicated by a succinct but reasonably explicit terminology.


Myocardial mitochondrial calcifiction in Reye's syndrome.

Ultrastructural and biochemical studies of myocardial tissue from a patient with the clinical and light microscopic features of Reye's syndrome showed evidence of intramitochondrial calcium deposition. The significance to recent experimental and clinical data concerning intramitochondrial calcium deposition.


Abdominal form of lymphomatoid granulomatosis.

A 54 year old white male died three months after hospitalization for hematemesis and melena due to a duodenal ulcer and two monthos after the  subsequent onset of progressive ascites and edema. At necropsy, lesions characteristic of "lympomatoid granulomatosis" as delineated by Liebow et al. were found in the liver, retroperitoneal lymph nodes, and mesenteric and retroperitoneal adipose tissue. This case appears to be the first case of "lymphomatoid granulomatosis" confined to the abdomen. This report further broadens the clinical spectrum of the newly delineated "lymphomatoid granulomatosis" and adds another situation to the differential diagnosis of space occupying lesions of the liver.


[New findings on the structure of chromosomes (author's transl)].

The structural element of eukaryotic chromosomes is the chromatin fibre consisting of histones and DNA. The chromatin fibre is about 100--200 A thick. One chromatid is built up from one chromatin fibre running through from one end to the other and laid in numerous irregular foldings. The chromatin fibre is a chain of nucleosomes. These are globular histone bodies around which the DNA winds. Nucleosomes can be observed in isolated chromatin fibrils as well as in thin sections of chromosomes after different modes of fixation. Prophasic chromosomes or early premature condensed chromosomes are thin uncoiled threads. With chromosome condensation a major coiling is seen. No constant regular arrangement of the chromatin fibril besides the major coils is observed. A rather diffuse decondensation takes place in ana- and telophase.


Premeiotic and early meiotic stages in the pollen mother cells of Eremurus and in human embryonic oocytes.

The premeiotic and meiotic stages are described in the pollen mother cells of the liliaceous plant Eremurus. In human oocytes from embryonic ovaries, the premeiotic and early meiotic stages up to dictyotene have been identified on morphological grounds. In Eremurus, in which each stage can be independently verified by the sequence of buds situated in a spiral, there is no indication of somatic pairing of homologous chromosomes, nor is there any sign of a premeiotic contraction of the chromosomes. The interphase following this mitosis is, in turn, succeeded by leptotene in which the DNA synthesis occurs, as determined by using autoradiography. This stage is followed by a "distance pairing" stage in which the homologous chromosomes lie parallel to each other at a distance. In typical zygotene, segments of chromosomes are paired intimately, others are unpaired, and the points at which pairing begins and ends are clearly visible. Each bivalent shows several pairing blocks. Pairing is completed at pachytene; diplotene which is characterized by the separation of the chromosomes follows. In mid-diplotene the chromosomes collect together in the so-called second contraction stage. The same meiotic prophase stages that occur in Eremurus, including the "distance pairing" stage, are found in the embryonic human oocytes. In the last premeiotic interphase, the chromosomes appear as condensed prochromosomes which unravel directly to form the leptotene chromosomes. In the oocytes, too, DNA synthesis seems to take place in leptotene.


Somatic stability of variant C-band heterochromatin.

Prominent C-band markers were found to be unchanged between different tissues of 9 individuals and during long term culture of 8 skin fibroblast and amniotic fluid cell strains.


Elimination of nucleolus organizers in a case of 13/14 Robertsonian translocation.

A Robertsonian translocation 45,XY, t(13q;14q) was detected in the leukocyte cultures of a phenotypically normal male. Silver staining technique for nucleolus organizer regions revealed that both acrocentrics involved in the translocation had lost their nucleolus organizers.


Tentative evidence for 3--4 haematopoetic stem cells in man.

Blood specimens from a random sample of 981 South African Negroid females were typed electrophoretically inter alia for their G-6-PD phenotypes, The allele frequency for GdB and GdnonB was found to be 0.8126 and 0.1874 respectively. Calculating the number of individuals expected for each phenotypic class, a highly significant deviation from the Hardy-Weinberg equilibrium became manifest, i.e. there was a deficit of 24.6% of heterozygotes and an excess of 12.3% of each of the two classes of homozygotes. Several possible reasons for this discrepancy e.g. the effects of pooling sub-samples, selection and misclassifications due to insufficient staining were examined and were found not be likely explanations for the observed phenomenon. Instead, the result is interpreted as due to only 3--4 stem cells which give rise to the haematopoetic system in man.


A photometric method for quantifying the polymorphisms in human acrocentric chromosomes.

Photometric measurements on photomicrographs of quinacrine mustard--stained metaphase chromosomes, processed by a reverse developing procedure provide quantitative data on the polymorphisms of human acrocentric chromosomes. The method described is intended for population studies. The method is easily reproducible, allowing comparisons of data obtained by different laboratories.


Prenatal diagnosis of globoid cell leukodystrophy (Krabbe's diseases). Third documented case.

A case of globoid cell leukodystrophy (Krabbe's disease) was diagnosed prenatally by demonstrating a profound deficiency of cerebroside beta-galactosidase in cultured amniotic cells. The diagnosis was confirmed in the fetus aborted in the 19th week. In the cell-free amniotic fluid, normal enzyme activity was found. This finding, which had been demonstrated in a previous case, is discussed.


A true microculture technique for human lymphocytes.

A true microculture technique utilizing only 0.01 ml of whole blood is presented. The blood is cultured in Eppendorf plastic microtubes in 1 ml of medium. This technique is easier, faster, and more economical than conventional methods. It is suitable for situations in which interphase cells or a small number (less than equal to 50) of metaphase cells are required.


Karyological characterization of a human lymphoblastoid cell line resistant to 6-thioguanine.

A mutant human lymphoblastoid cell line, Raji-TG, resistant to 10micron g 6-thioguanine (TG)/ml was produced from wild-type cells after exposure to ethylmethane sulfonate. The Raji-TG cells showed their failure to incorporate 3H-hypoxanthine, only 2% as much hypoxanthine guanine phosphoribosyl transferase (HPRT) activity as wild-type cells, and no revertant in HAT selective medium containing bypoxanthine, aminopterin, and thymidine. Raji-TG cells, which were maintained routinely in regular medium lacking TG for as long as 2 years, still retained resistance to the drug and inability to grow in HAT medium. A fusion of Raji-TG cells and mouse cells resistant to 5-bromodeoxyuridine and lacking thymidine kinase formed hybrids, and the resulting hybrid colonies proliferated in HAT medium. These observations strongly supported the hypothesis that Raji-TG line cells might be originated from a mutational event with deficiency of HPRT. Both parental and the mutant have a modal chromosome number of 49 with a remarkably stable karyotype. Excess chromosome materials are found in chromosomes 1, 5, 7, 14, and 16. Chromosome 8 is completely missing, but is represented by two respective isochromosomes of the short and long arms of No. 8. Five different marker chromosomes could be distinguished, and most of their origin has been determined. Isolation of Raji-TG X mouse hybrid clones which contained one of each marker chromosome is of considerable value in mapping human genes on regions within particular chromosomes.


Differential chromosomal radiosensitivity within the first G1-phase of the cell cycle of early-dividing human leukocytes in vitro after stimulation with PHA.

Human leukocyte cultures were irradiated with 200 RX-rays before the addition of phytohemagglutinin (PHA) in the Go-stage and at different times up to 25 h within the first G1-phase of the cell cyle after the addition of PHA. The results of the analysis of chromosomal aberrations show that the frequencies of dicentric chromosomes increase significantly when leukocytes leave the Go-stage, reaching a miximum yield of aberrations about halfway through the first G1-phase. After that, toward the end of the G1-phase, the frequencies of dicentric chromosomes decrease again to a level similar to that found in the Go-stage. Different possible explanations for the differential chromosomal radiosensitivity of human leukocytes within the first post-stimulation G1-phase are discussed.


Evidence for two additional common alleles at the PGM1 locus (phosphoglucomutase--E.C.: 2.7.5.1). A comparison by three different techniques.

Lysates of erythrocytes, leukocytes, lymphocytes, and extracts of sperms were investigated for the PGM1 isozymes by three techniques: starch gel electrophoresis, high voltage thin-layer agarose gel electrophresis, and thin-layer isoelectric focusing on polyacrylamide gel. On starch, only the well known common phenotypes 1, 2-1, and 2 were demonstrable. On agarose, different distances of the two main cathodal bands (a,b) among the phenotypes 2-1 were noted. Furthermore, on agarose, some types considered as homozygous on starch gel had a single, sharp banded pattern while others were broad and blurred. Optimal separation was achieved by isoelectric focusing on polyacrylamide gel. In 291 leukolysates, 10 different phenotypes were identified. These are considered as gene products of 4 different common allesles at the PGM1 locus as suggested by preliminary family investigations. In a random population from Hessen these four alleles had the following frequencies: PGM1al 0.6186, PGMa21 0.1718, PGMa31 0.1426, and PGMa41 0.067, The preliminary designation a1, a2, a3 and a4 was chosen as the assumed polymorphism was demonstrated on acrylamide and agarose. The sum of the frequencies PGMa11 and PGMa31 (the gene products of which have apparently the same electrophoretic mobility on starch) is similar to the frequency of the old PGM11 allele (0.757) in Caucasoids, PGMa21 and PGMa41 have a frequency of 0.2388 corresponding with the frequency of the old allele PGM21.


Duchenne muscular dystrophy. A population study.

By a general survey in the hopitals of northeast Italy, Duchenne cases have been located and identified over a 20-year period. In a more restricted area screening for Duchenne carriers has been carried out in affected families. This procedure made possible an exact estimate of the incidence rate, prevalence rate, and mutation rate in a large sample of population. Prevalence rate was found to be 34x10(-6), incidence rate about 28x10(-5), while mutation rate was found lower than 50x10(-6) by the direct method. The discrepancy between the results obtained by the Haldane formula and those obtained by the direct method for the estimate of the mutation rate is discussed.


A possible association of long Y chromosomes and fetal loss.

Long Y chromosomes is a relatively unbiased large sample of newborn infants were measured. The proportion of prior abortions was increased twofold in mothers of long Y infants compared to the control in the Caucasian sample. Our results indicate that an increased length of Y chromosome may be an important cause of fetal loss.


Klinefelter's syndrome and incontinentia pigmenti Bloch-Sulzberger.

We report a newborn with incontinentia pigmenti Bloch-Sulzberger and male phenotype. Chromosome analysis revealed a Klinefelter's syndrome 47,XXY. These findings are compatible with the hypothesis of dominant sexlinked genes carried on the X-chromosome in this disease.


The 11q -- syndrome.

An eighth case of terminal deletion of the long arm of chromosome eleven (11q--) is reported to emphasize both the distinctive facies, but otherwise non-specific nature of this disorder, and the female preponderance of affected patients. Growth and mental retardation, congenital heart disease and telecanthus are the other most constant features. The authors' experience with 3 unrelated cases in less than 2 years suggests that this syndrome is underdiagnosed.


Clinical and cytogenetic studies of two infants with partial monosomy G.

Clinical and cytogenetic studies are reported in two infants with a stable ring G chromosome. Identification of the abnormal chromosomes was performed by the G-banding and the Q-banding methods.


Non-random association of trypsin-banded human acrocentric chromosomes.

This paper deals with a computer-aided study of the associations between acrocentric chromosomes as well as between those other chromosomes which in our investigations were revealed to be significantly closer to each other than random. The chromosome pairs were identified by a trypsin-banding technique. The method used has been elaborated previously with the specific aim of determining associations in a manner that avoids all subjective criteria. The tendency for association between homologous chromosomes is in decreasing order: 21 and 13 greater than 1 greater than 14, 18 and 19 greater than 17. Among the nonhomologous acrocentric chromosomes the significant tendencies for associations are between D-D: 13-14 greater than 13-15 greater than 14-15; between D-G: 13-21 greater than 14-21 greater than 13-22 greater than 15-22. The implication of the different tendencies to associate are dicussed in terms of aetiology of numerical and structural chromosome abnormalities.


Different N-terminal amino acids in the MN-glycoprotein from MM and NN erythrocytes.

The major human erythrocyte membrane (MN-) sialoglycoprotein was purified from MM, MN and NN cells using detergent gel and ion exchange chromatography. N-terminal analyses with dansyl-chloride revealed serine in preparations from MM and leucine in those from NN erythrocytes, whereas glycoprotein isolated from MN cells contained both the above amino acids. These data strongly suggest that the above residues may represent the structural difference between the M and  N antigens. Evidence was also obtained that the Ss-glycoprotein,  which is associated with "N" activity, exhibits the same N-terminal amino acid (leucine) as the MN glycoprotein from NN cells.


Aanlysis of the frequency and distribution of sister chromatid exchanges in cultured human lymphocytes.

Lymphocytes from 20 notmal subjects (11 male and 9 female) were examined for the frequency and location of sister chromatid exchanges (SCE) by the BrdU--Giemsa method. The mean frequency of SCE was 6.37 with little significant variation. One subject had a high number of exchanges in chromosome 1 while the remainder showed a random distribution of exchanges between chromosomes. The frequency of exchanges generally increased with chromosome length. However, chromosome 1, 2 and the B group had more exchanges than expected while the E, F and G grous had less than expected. The distribution of exchanges in chromosomes 1, 2 and the B group was non-random with a concentration of exchanges below the centromere and to a lesser extent on the distal portion of the long arm. The majority of exchanges appeared to occur at the junction between the dark and light G bands. It is suggested that the concentration of exchanges may reflect differences in BrdU incorporation along the length of the chromosome.


Partial trisomy 10p and familial translocation t(7;10)(p22;p12).

A girl with partial trisomy for the short arm of chromosome 10(p12leads to pter) due to mal chromosome segregation in the father 46,XY,t(7;10)(p22;p12) is described. The major abnormalities in this case are: mottled skin, mid-facial hypoplasia, low percentiles for weight, length, and head circumference, and club feet.


A  chiasma map of man.

By fitting compounds beta distributions to chiasma frequencies the physical map obtained from banded chromosomes has been converted into a chiasma map giving the distribution of observed chiasmata in relation to several hundred cytological bands, assuming proportionality of mitotic and meiotic chromosomes. This is a genetic map if there is a precise correspondence between sites of chiasmata and crossing-over. However, if there is appreciable preanaphase movement of chasmata, then the chiasma map is a serious distortion of the genetic map. Predictions from the chiasma map can be confirmed or refuted only by genetic evidence for which the estimates of this paper serve as initial values to begin maximum likelihood iteration.


Origin of human trisomics and polyploids.

A mathematical theory is derived for the distribution of heteromorphisms in trisomics and polyploids. Applied to the sparse literature, it appears that most trisomy 21 is due to first division maternal nondisjunction, although there are case reports of second division nondisjunction, both paternal and maternal. Most triploids appear to be due to dispermy or failure of the first meiotic division in the oocyte. The need for larger systematic samples is stressed. This maximum likelihood analysis gives great resolution to epidemiological studies, permitting discrimination of etiological factors acting on fathers and mothers, at different meiotic stages, and on dispermy.


Further studies on the biological properties of guinea-pig IgG1 antibodies. III. Haemolytic efficiency in vitro.

The capacity of non-reciprocally contaminated guinea-pig IgG1 and IgG2 antibodies for sensitizing antigen-coated sheep erythrocytes for lysis was studied in the presence of serial dilutions of normal guinea-pig serum as the source of complement. IgG1 antibodies were highly efficient, provided complement was little diluted and not heated at 56 degrees. Chelation of Ca2+ by EGTA affected lysis of IgG1-sensitized cells by only 50%, while completely blocking lysis of IgG2-sensitized cells. The F(ab')2 fragment of IgG1, in contrast to the F(ab')2 fragment of IgG2, was almost as efficient as the parent antibody.


The effect of immunological adjuvants on the relative affinity of anti-protein antibodies.

Inbred mice of a strain (B1OD2 new) known to produce either no detectable antibody or antibody of low affinity to two protein antigens administered in saline, were immunized with human serum transferrin (HST) in one of nine adjuvants. Such immunization increases the level and relative affinity of anti-HST antibody. The adjuvants used varied in the degree to which they augmented these parameters of the antibody response--that is, FCA and FIA were capable of inducing high levels of high affinity antibody, whereas other adjuvants elicited lower levels of high affinity antibody. The possibility is discussed that substances with adjuvant activity may effect antibody production at two stages: (1) at the stage of antigen selection of cells for proliferation and (2) at the stage or proliferation of antibody producing cell precursors.


The response of protein-deficient mice to tetanus toxoid. Effects of antigen dose, adjuvants, period of deprivation and age on antibody production.

The effects of a 4% albumin diet initiated at weaning on primary and secondary responses to AIPO4-adsorbed and soluble tetanus toxoid (TT) were studied in C57BL mice. Responses of both groups were directly proportional to the dose of antigen over most of the range tested, but at very low doses protein-deficient mice produced higher primary titres than normal mice. In the primary response AIPO4-adsorption of the antigen essentially increased the effective dose irrespective of the diet, but after secondary challenge responses to soluble TT were more severely affected by the diet. Normal secondary titres to AIPO4-adsorbed TT were achieved when deficient mice were given high doses of antigen. Diet also affected the relative proportions of IgG and IgM produced in most responses. Gram-negative bacterial vaccines and lipopolysaccharide increased antibody production in both groups of mice. The low protein diet produced less dramatic effects when initiated at the time of inoculation or later, and mice maintained for longer on the diet produced more nearly normal titres. Mechanisms which may explain these findings are discussed.


Passive cutaneous anaphylaxis and vasoactive amine challenge in nude (nu/nu) mice. A comparison with nu/+, axenic and young normal animals.

Recent suggestions of a thymic origin or thymo-dependent differentiation of tissue mast cells prompted an investigation in the athymic nude (nu/nu) mouse. The outbred nu/nu examined were found to possess mast cells in at least comparable numbers to the phenotypically normal nu/+. These nu/nu were superior to nu/+ as recipient for mast cell-dependent, long latent period (IgE-type), passive cutaneous anaphylactic (PCA) reactions. A variety of studies performed, including competition with nu/+ serum, thymic restoration, quantitation of nu/+ homocytotropic antibody responses, comparison with axenic or young mice and time-course studies of skin sensitization suggested that the higher PCA titres in nu/nu skin were not entirely due to a lack of competitive inhibition of mast-cell sensitization. The nu/+ used in these studies were in fact poor IgE recipients, but were somewhat more sensitive than nu/nu to hypovolaemic shock induced by histamine and serotonin mixtures. Pretreatment with Bordetella pertussis greatly enhanced the sensitivity of nu/+, axenic, holoxenic and young normal mice to the vasoactive effects of histamine and serotonin, but was somewhat less effective in nu/nu and old mice.


Enthalpy-entropy compensation in dinitrophenyl--anti-dinitrophenyl antibody interaction(s).

The effect of varying the temperature over a wide range (-3 dergees -67 degrees) on the binding of xi-DNP-L-Lysine to bovine colostral anti-DNA IgG1, and also rabbit anti-DNP IgG revealed non-linear van't Hoff plots. The extent of the curvatures were found to be indicative of large positive heat capacity changes; and the thermodynamic parameters, calculated using a non-linear least-squares computer procedure for these anti-DNP antibody preparations, revealed an enthalpy-entropy compensation mechanism for hapten-antibody binding. The enthalpy factor was found to be the primary contributor for the binding process at low temperatures, but at increasing temperatures the entropy factor assumed greater importance. At physiological temperature (37 degrees), the entropy factor was the major contributor to the free energy of reaction for rabbit anti-DNP IgG, while for bovine colostral anti-DNP IgG it was predominant at temperatures higher than 37 degrees.


Induction of acute and chronic arthritis by intra-articular injection of preformed collagen-anticollagen complexes.

Three groups of rabbits were injected intra-articularly into the knee joints with preformed complexes of hydroxamated collagen and antiserum to denatured collagen respectively, with hydroxamated collagen and normal serum, hydroxamated collagen, anticollagen serum or saline as controls. From twelve rabbits, receiving only one injection and investigated 8 h later, only the joint tissues of rabbits which received immune complexes showed acute arthritis with severe infiltration of polymorphonuclears, leucocyte thrombi in vessels and haemorrhages. From six rabbits, receiving two consecutive injections (day 0 and day 2) and investigated 12 h after the last injection, only the joint tissue of rabbits which received immune complexes showed subacute-chronic arthritis. From sixteen rabbits receiving four consecutive injections day 0, day 2, day 7 and day 14) and investigated 7 days after the last injection, only the joint tissue of rabbits which received immune complexes showed severe chronic arthritis with infiltration of plasma cells, lymphocytes and nodule-like accumulation of lymphocytes whilst their joint fluid showed additionally a distinctly increased number of polymorphonuclears (3-15 x 10(6)) which differed with P less than 0-01 statistically from all controls.


Leucocyte chemotactic activity in the parallel bioassay of guinea--pig lymphokines.

This paper describes the application of parallel bioassay to determine the extent to which the leucocyte chemotactic activity of guinea-pig lymphokine preparations is associated with their lymphocyte mitogenic, inflammatory (increased vascular permeability) and macrophage migration inhibitory activities. A convenient test of chemotactic activity was devised whereby Coulter counter determinations were made of the number of peritoneal exudate cells passing through a Nuclepore membrane into the medium of the lower (test) compartment of a chemotaxis chamber. Symmetrical parallel line (2+2) dose assays were used to obtain potency ratio estimates of the chemotactic activity of seven lymphokine preparations whose mitogenic, inflammatory and migration inhibitory activities were already known. Statistical analysis of the results revealed a clear dissociation of chemotactic activity from mitogenic and migration inhibitory activities; but with six of the seven lymphokine preparations, a marked similarity was revealed between their chemotactic and inflammatory activities. Cytological studies showed that although the lymphokine preparations were chemotactic for different cell types, there was a preferential migration of neutrophils and the smaller mononuclear cells. The demonstration by parallel bioassay of an association between the ability of lymphokine preparations to increase vascular permeability in vivo and to promote chemotaxis of leucocytes in vitro is viewed in relation to the possible role of lymphokine in inflammatory processes.