The activities of brain dopamine-beta-hydroxylase and catechol-O-methyl transferase in schizophrenics and controls.

It has been suggested that deterioration of central noradrenergic pathways may be responsible for the production of certain schizophrenic symptoms, and that such a degeneration might be reflected in lowered dopamine-beta-hydroxylase (DBH) activity in the brains of schizophrenics. The present study revealed that in rats lowered DBH activity was a sensitive index of noradrenergic degeneration. In the postmortem brains of 12 controls and 12 schizophrenics, however, no significant difference in DBH activity between controls and schizophrenics was found. DBH activity was relatively unstable postmortem and adversely affected by neuroleptic drugs, and these factors may have contributed to the previous finding of lowered DBH activity in the brains of schizophrenics. The activity of catechol-O-methyl transferase, which has also been previously reported as low in the brains of schizophrenics, was found to be no different in the controls of the present study.


The effects of atropine on the tolerance and the convulsions seen after withdrawal from forced barbital drinking in the rat.

Male rats were forced to drink a barbital solution as their only drinking fluid for 33 weeks. During the last part of the treatment the average dose of barbital was around 200 mg/kg/day. In the abstinence period after barbital treatment, tolerance was recorded with a hexobarbital anaesthesia threshold utilizing an EEG criterium. Convulsions were recorded in jiggle cages. On days 3 and 28 of the abstinence period, i.p. pretreatment with atropine (2, 4, and 8 mg/kg) was given 1.5 h before threshold determinations. The barbital treatment induced a clear tolerance to the hexobarbital, which still could be detected on day 28 of abstinence. Atropine (8 mg/kg) reduced the hexobarbital threshold in tolerant and in control animals at both the time of maximum tolerance (day 3) and later during abstinence (day 28). The magnitude of the response was greater in tolerant animals, but no parallel shift in the dose-response curve was seen. The convulsions during abstinence were reduced for at least 8 h after atropine treatment (8mg/kg) on day 3. These results support the hypothesis that cholinergic mechanisms are involved in the changes induced by chronic barbiturate treatments.


Parkinsonism by haloperidol and piribedil.

Three groups of schizophrenic patients were treated with haloperidol, with a low dose of piribedil (a dopamine agonist), and with a combination of the two treatments, respectively. After a few days, all 7 patients treated with the drug combination showed marked rigidity and akinesia, while patients treated with haloperidol alone (4) and piribedil alone (4) showed either mild or no symptoms of parkinsonism. The drug combination induced mainly an akinetic-hypertonic syndrome, while tremors were absent or mild. The results suggest that low doses of the DA-agonist potentiate the extrapyramidal side effects of haloperidol by acting on self-inhibitory DA receptors, thereby blocking the compensatory increase in dopaminergic firing elicited by the neuroleptic agent.


Interaction between d-amphetamine and ethanol with respect to locomotion, stereotypies, ethanol sleeping time, and the kinetics of drug elimination.

The interaction between d-amphetamine and ethanol with respect to locomotor activity, stereotyped behavior, and sleeping time was investigated in rats. Ethanol 0.8 g/kg i.p. enhanced and prolonged locomotor activity produced by d-amphetamine 1 mg/kg s.c. The increased motility after 5 mg/kg d-amphetamine was not influenced by alcohol 0.8 g/kg i.p. or 3.2 g/kg orally, but slightly protracted. Stereotyped head and paw movements, as well as stereotyped licking, were distinctly strengthened and protracted by 3.2 g/kg ethanol orally. The modified d-amphetamine motility and stereotypies can be explained by alcohol-induced proloneation of the life of d-amphetomine. The effect is produced by alcohol's inhibition d-amphetamine p-hydroxylation in rat liver. After 3.2 g/kg ethanol i.p., the sleeping time of male rats amounted to 153 min. Simultaneous administration of 5 mg/kg d-amphetamine s.c. reduced the sleeping time to 84 min. This is obviously based on a central antagonism.


Effects of chlordiazepoxide, amitriptyline, imipramine, and their combinations on avoidance behaviour in mice.

Chlordiazepoxide, imipramine, and amitriptyline, given alone or in combination, were tested in mice subjected to 5 daily 100-trial avoidance sessions in the shuttle-box. When the drugs were given alone, chlordiazepoxide and the lower doses of imipramine facilitated avoidance behaviour. The higher doses of the two antidepressants impaired avoidance behaviour. Mixtures of chlordiazepoxide and imipramine produced some facilitating effects, while depressant effects prevailed in the chlordiazepoxide-amitriptyline combinations.


Facilitating effects of chlordiazepoxide on locomotor activity and avoidance behaviour of reserpinized mice.

Chlordiazepoxide increased the spontaneous locomotor activity of both normal and reserpinized mice and facilitated the avoidance behaviour of mice pretreated with reserpine. These effects of chlorodiazepoxide on reserpinized animals were unexpected, since they are usually considered characteristic of antidepressant drugs.


Facilitating effects of chlordiazepoxide on the performance of mice in an inhibitory avoidance task.

Inhibitory avoidance behaviour of mice was studied by using an automated procedure. Animals were subjected to five 15-min sessions. Facilitation of the inhibitory avoidance behaviour was observed following the administration of chlordiazepoxide at doses which did not produce significant effects on spontaneous locomotor activity.


Instinctive predatory behavior of the ferret (Putorius putorius furo L.) modified by chlordiazepoxide hydrochloride (Librium).

The predatory behavior of ferrets (Putorius putorius furo L.) consists mainly of instinctive behavioral patterns that are elicited by simple external stimuli. For the ferret, the time needed to catch and kill rats depends on the size of the rats in relation to that of the ferret. Killing success decreases with a relative increase in prey size. Chlordiazepoxide hydrochloride injections (1 mg/kg, i.m.) modified this behavior. Drugged ferrets needed less time and less bites to kill relatively large rats; killing success was also increased. Chlordiazepoxide seemed to disinhibit the ferrets when they were presented with large rats, which they normally attack more cautiously.


Effects of benzazepine (Sch-12679) on shock-induced fighting and locomotor behavior in rats.

Benzazepine (Sch-12679) reduced the shock-induced fighting behavior of rats in a dose-dependent fashion. However, the drug also impaired both locomotor behavior and rotorod performance. These results suggest that the aggression suppressive effects of Sch-12679 may be mediated by drug-induced sedation.


Monoamine oxidase activity in different density gradient fractions of human platelets.

Monoamine oxidase (MAO) activity measured in human platelets is reportedly altered by such drugs as epinephrine, lithium carbonate, and imipramine, and also reduced in a number of clinical disorders. To evaluate whether MAO activity might differ in platelet subpopulations, density gradient centrifugation with arabino-galactan was used to prepare four platelet fractions that differed in weight and volume. MAO activity in the lightest and smallest platelet subpopulation was approximately one-half that in the heaviest and largest subpopulation. Because platelet weight and size are thought to be related to platelet age, it is possible that some drug effects on platelet MAO activity might represent changes in platelet turnover. Factors other than platelet turnover rates may contribute to individual differences in platelet MAO activity, however, since one group of individuals with markedly reduced platelet MAO activity exhibited no shift in the proportion of lighter versus heavier platelets nor in the relative amount of MAO activity in each density gradient subfraction.


A genetic analysis of the hyperthermic response to d-amphetamine in two inbred strains of mice.

A genetic analysis of amphetamine-induced hyperthermia was conducted in inbred mice of the strains Balb/c and C3H and in their F1F2 and backcross generations. The results of biometric analysis indicate that the effect of amphetamine on body temperature is genetically determined. The mode of inheritance characterized by a partial dominance (Balb/C over C3H strain). However, a possible maternal effect of C3H can overcome the dominant effect in male progenies and inhibit amphetamine hyperthermic effect.


Pentobarbital, promazine, d-amphetamine, and scopolamine effects on behavior under multiple and primed schedules of reinforcement.

Pigeons responded under compound fixed-interval (FI) fixed-ratio (FR) schedules of food presentation. Distinctive discrimininative stimuli were either continuously present during each component schedule (multiple FI FR) or were present only for a brief period at the beginning of each component (primed FI FR). Similar rates and patterns of responding were maintained under the multiple and primed schedules. Pentobarbital, scopolamine, and d-amphetamine decreased FR responding, but promazine had little effect at the doses studied. d-Amphetamine and promazine increased FI responding at certain doses, pentobarbital had little effect, and scopolamine decreased responding. There were no systematic differences in the effects of drugs under the multiple and primed schedules, in spite of the differences in discriminative stimuli under the conditions.


Mandibulogram as a measure of stereotyped behavior in the rat.

A proposal of a device for continuous monitoring of the movements of the rat's mandible is outlined. Its utility in experimental psychopharmacology is suggested for monitoring of the effect of neuroleptics and antidepressants on oral stereotypies as induced by CNS stimulants.


Contrast agents for myelography: clinical and radiological evaluation of Amipaque and Pantopaque.

The diagnostic quality and side effects of Amipaque and Pantopaque as myelographic contrast agents were compared prospectively using the identical protocol in 167 cases (117 Amipaque, 50 Pantopaque). Good ratings were attained in 74% of Amipaque and 76% of Pantopaque examinations. Demonstration of nerve rootlets in the cauda equina and filling of lumbar root sleeves were superior with Amipaque. Amipaque more easily demonstrated the high posterior cervical subarachnoid space and the anterior and posterior margins of the cervical spinal cord. The incidence of postmyelographic headache was 38% with Amipaque and 32% with Pantopaque. Nausea and vomiting were more common with Amipaque. Two patients experienced grand mal seizures after examination sith Amipaque.


The effect of hydration on the acute and chronic complications of aqueous myelography. An experimental study.

The effect of hydration on the incidence of complications from myelography with aqueous media was studied. Myelography was performed with methylglucamine iocarmate in dehydrated and vigorously hydrated monkeys. The incidence of seizures and the severity of arachnoiditis were significantly greater in the dehydrated animals. The authors suggest that patients be permitted fluids ad lib. prior to myelography with aqueous media, or in some cases be given fluids intravenously.


Systematic patient-dose errors for 4- and 10-MeV microwave linear accelerators associated with rectangular collimator settings.

Systematic patient-dose errors relating to standard equivalent-square approximations and movable collimator-exchange effect were evaluated for rectangular fields of photon beams from 4- and 10-MeV microwave electron accelerators (Varian Clinac 4 and Clinac 18). Errors approached 2.5% at nominal treatment depths for highly elongated rectangular fields. The collimator-exchange effect should be considered when (a) evaluating ionization-chamber stem effect, (b) specifying relative output factors for rectangular fields, and (c) evaluating equivalent-square-field algorithms.


A simple method of protecting the eye from scattered radiations during mantle-field therapy.

The intensity and quality of scattered radiations incident on the eye during mantle-field therapy were measured for 4-MV x rays. Beam-shaping appliances were found to introduce considerable soft scatter. Eye shields reduce radiation exposure from the anterior field approximately threefold.


Neurologic computed tomography in a defined population group.

A total of 766 residents of Olmsted County, Minnesota, underwent neurologic computed tomography (CT) from June 1973 through 1976; 981 scans were performed. The number of CT scans per 1,000 population increased each year and, during the period studied, the average rate based on the initial scan in each case was 2.4 and the rate based on all scans was 3.1. The age-specific rates were greatest among patients 65 years old or older. If CT use plateaus at about 6 scans per 1,000 population, then under conditions similar to those in this community, a population of approximately 400,000 would be required to assure adequate use of a CT scanner for investigating neurologic disease.


Scattered radiation from beam modifiers used with megavoltage therapy units.

The magnitude and distribution of scattered radiation produced by scatterers inserted into megavoltage therapy beams, including the beams from an 8MV medical linear accelerator and a 60Co teletherapy unit, were investigated. The intensity distribution of scatter depends on the distance from the scatterer to the measurement plane (retraction distance) and also, to a lesser extent, on the atomic number of the scattering material. The effective energy of the scattered radiation was determined by depth dose measurements in tissue equivalent material using thermoluminescent dosimeters and was found to increase with photon beam energy.


Cost analysis of aggressive breast cancer screening.

It is estimated that mammographic and physical examination (PE) screening would cost $3,866 per person year gained; screening with PE alone would cost $4,550. Sixty thousand person years are gained with combined screening, and 24,000 with PE alone per million women screened. The cost per cancer found is $9,046; for each highly curable cancer $26,961, and for each death averted $61,100. An estimated 16 years are added to each life saved. The cost per patient screening examination, using all techniques, is $20.04.


Benign duodenocolic fistula due to duodenal diverticulum: report of two cases.

Two cases of benign duodenocolic fistula resulting from duodenal diverticula are presented. In both cases, the diverticula were located on the outer border of the second portion of the duodenum. The upper gastrointestinal study is the easiest and most useful examination for diagnosis. Hypotonic duodenography and the barium enema complement the upper series and serve to differentiate benign from malignant fistulas.


Differences in prostaglandin formation between thymocyte subpopulations.

The concentration of prostaglandin E and the activity of prostaglandin synthetase were determined in mature and immature mouse thymocytes. Hydrocortisone resistant thymocytes, or thymocytes separated from the immature cell population after agglutination of the latter by peanut agglutinin served as a source of mature thymocytes. It was found that mature thymocytes contain a much higher concentration of prostaglandin E and have an increased activity of prostaglandin synthetase than immature cells.


1-phenyl-3-pyrazolidone: an inhibitor of cyclo-oxygenase and lipoxygenase pathways in lung and platelets.

1-phenyl-3-pyrazolidone (phenidone) is a commercially available reagent used in the photographic industry. When tested as an inhibitor of arachidonic acid metabolsim in platelets and lungs it was found to be effective against both the cyclo-oxygenase and lipoxygenase pathways. It is suggested that this compound may be a useful pharmacological tool.


About the existence and endings of nerve fibres in the Cebus apella monkey's upper lip.

In the present research, fibres and nerve endings of upper lip of the Cebus apella monkey have been studied. Upper lip of 8 Cebus apella were analysed. The pieces were prepared according to the technic of Castro's silver impregnation and submitted to serial sections 8 micra thick. Our results permit to conclude that the Cebus apella monkey's upper lip has a great number of free nerve endings, between connective and epithelial layers in the mucosa and in the skin. The aspects of nerve fibres and their free and organized endings, like Meissner's corpuscles, in the upper lip mucosa of the monkey, allow comparison of similarity with those of man. The nerve endings in the lip skin of the Cebus monkey are also abundant, characterizing the hair follicles and sebaceous glands innervation and the free nerve endings encountered in the connective tissue as well as in the sub-epithelial layer.


[Low doses of insulin--comparison between hyperosmolar nonketotic coma and diabetic ketoacidosis (author's transl)].

The authors present a comparison between the results achieved in the treatment of 11 cases of nonketotic hyperosmolar "coma" and 13 cases of diabetic ketoacidosis using low doses of intramuscular insulin hourly. Surprisingly both, larger amounts of insulin and longer periods were needed to compensate the metabolic disturbance of the nonketotic hyperosmolar "coma" cases when compared to the ketoacidosis ones. The data obtained in this study suggest a possible direct relationship between the initial urea levels and the total amount of insulin needed to reduce the initial glycemia to a normal glycemic level.


On the process of activation and inactivation of dog skeletal muscle glycogen synthase.

The presence of additional forms of glycogen synthase (UDPG: alpha-1,4-glucan alpha-4-glucosyltransferase) besides the I form (independent on glucose-6-P for activity) and the D form (dependent on glucose-6-P for activity) long ago described, is inferred from patterns of their interconversions obtained by processes of phosphorylation and dephosphorylation. An intermediate form more phosphorylated than the I form and less than the D form, which is completely inactive in these assay conditions, and a superphosphorylated form, more phosphorylated than the D form and also inactive even in presence of 0.01 M glucose-6-P are described.


Presence of glucuronyltransferase activity in human lymphocytes.

Human lymphocytes contain glucuronyltransferase activity. This enzyme requires a high concentration of uridine diphosphoglucuronic acid and can be measured with testosterone as a substrate. This finding is of interest because glucuronidation is a deactivating process for many pharmacologically active compounds that are substrates of glucuronyltransferase.


Synthesis of immunoglobulin by normal and antigenically stimulated fetal sheep.

The rate of appearance, quantity and immunochemical character of serum immunoglobulins which appear normally during the development of fetal sheep and following the injection of antigens at different stages of gestation have been studied. After 70 days' gestation a percentage of normal fetal sheep synthesise IgM. Although the concentration of IgM in the circulation of these animals was very low, the precentage with IgM increased with fetal age. A few late term fetuses were detected which also had IgG1 in their circulation, although none were detected with IgG2 or IgA. Fetuses injected with antigens before 71 days' gestation only synthesised IgM, while fetuses injected after 79 days' gestation synthesised both IgM and IgG1. Neither IgG2 nor IgA were detected by single-radial immunodiffusion analyses during the first 14 days of primary immune responses to a variety of antigens, although trace amounts of IgG2 were detected late in responses occurring in older fetuses. The immunoglobulins synthesised by antigenically stimulated fetal sheep appeared identical to adult sheep 19S IgM, 7S IgG1 and 7S IgG2 respectively, when analysed by immunoelectrophoresis, isoelectric focusing and G200 Sephadex column chromatography.


Virus-like particles associated with porcine epidemic diarrhoea.

Porcine epidemic diarrhoea type II was reproduced in experimental pigs of various ages by oral dosing with minced intestine from a naturally occurring case of the disease. Virus-like particles which probably represent an unidentified coronavirus were seen by electron microscopy in the faeces and intestinal epithelium of infected animals.


Do penicillamine and Myocrisin act the same way in rheumatoid arthritis?

Our observations, as well as similarities between penicillamine and Myocrisin in clinical action and side effects in RA make it not unreasonable to think that thiomalate may have a penicillamine-like effect. Only a controlled clinical trial with thiomalate in RA can provide an answer to this question.


Gold treatment at an early stage of rheumatoid arthritis.

The progression of erosive X-ray changes over a period of 5--6 years was evaluated in 39 patients exposed to a mean dose of 2030 mg aurothiomalate during the maintenance period. The cause for the low dose was the initial high incidence of side-effects. The progression of erosions was highest in patients with the low dose of gold in the initial stages of the disease. The best result in preventing development of erosions was achieved in patients with the high dose of gold in the early phase of the disease. It appears that gold treatment prevents the progression of the erosoins. The earlier the inception of treatment, the better the result.


Comparison of two maintenance schedules of chrysotherapy in rheumatoid arthritis: preliminary report.

Comparison of maintenance injections of sodium aurothiomalate given at two-week or four-week intervals revealed no significant clinical or radiological differences over a six-month period. Higher serum gold levels were achieved with the more frequent injections and these were associated with a more pronounced fall of ESR during maintenance therapy. Whether this has any special implications for the subsequent progress of patients treated by the two regimes remains to be determined.


Perennial rhinitis - its causation and treatment, a trial of a new formulation of sodium cromoglycate.

A double blind cross over study on the effect on 2% aqueous solution of sodium cromoglycate in perennial rhinitis has been performed in 37 patients. It is concluded that SCG solution is a useful and effective therapy irrespective of whether the disease is due to exogen allergy or vasomotoric (intrinsic) type.


Phlebography in long-term catheterization of the subclavian vein. A retrospective study in patients with severe gastrointestinal disorders.

The frequency of superior central venous thrombosis was studied in a consecutive retrospective series of 27 patients with severe gastrointestinal disorders in whom long-term catheterization of the subclavian vein for parenteral nutrition was carried out. The patients had 35 periods of catheterization ranging from 14 to 766, mean 86, days and a total of 51 catheter periods. Only one patient showed clinical signs of thrombosis in spite of phlebographic findings revealing seven cases of central venous thrombosis. Recanalization was not seen. Exchange of catheter was performed 17 times in 10 patients using the Seldinger technique. This did not influence thrombosis rate. Septicaemia was found in five patients subsiding after catheter exchange. No fatalities occurred, and no correlation between the septicaemia and thrombosis rate was found. Catheters used for more than 100 days showed changes of mechanical properties. It is therefore advisable to exchange catheters after 3 months' use by the Seldinger technique. The discrepancy between the clinical and phlebographic findings emphasizes that repeated subclavian catheterization should be preceded by bilateral phlebography.


Waldenström's macroglobulinaemia with Ig E M-component.

A case of Waldenström's macroglobulinaemia with Ig E M-component was presented. A 76-year-old Japanese woman had a history of the operation for mammary carcinoma. Although neither lymphadenopathy nor hepatosplenomegaly was present, the immunohaematological findings typical for Waldenström's macroglobulinaemia were observed in this patient. Coexistence of the Ig M and Ig E M-components was recognized in the patient's serum protein. Positive reaction for FITC-conjugated anti-epsilon or rhodamine-conjugated anti-mu was noted in proliferating lymphoplasmacytic cells of the patient's bone marrow, but these reactions were not simultaneously observed in a single cell. The finding suggests that two separate populations of M-component-producing cells were present.


Myelomatosis after phenytoin therapy: a chance association?

The occurrence of a monoclonal gammopathy followed by IgG-lambda multiple myeloma is described in a patient receiving diphenylhydantoin therapy for 20 years for epilepsy. Despite the known association between the drug and the development of immunosuppression and lymphoma, we regard the association recorded in this case to be coincidence. It is suggested that periodic examination of the serum proteins in patients receiving the drug may be useful in detecting early aberrations of the immune system in these individuals.


Recurrent Pseudomonas infection associated with neutrophil dysfunction.

A 72-year-old male is described with a history of 4 episodes of Pseudomonas aeruginosa sepsis and chronic otitis media caused by pseudomonas species. In vitro testing of the patient's polymorphonuclear leukocytes (PMNs) revealed profoundly abnormal chemotactic responses and defective intracellular killing of Ps. aeruginosa, Staphylococcus aureus and Escherichia coli. Chemiluminescence production by the patient's PMNs in response to opsonized zymosan as well as endotoxin stimulated nitroblue tetrazolium dye reduction were markedly depressed. These data indicate the presence of a profound, apparently acquired, defect in PMN function in an elderly male. Detailed evaluation of adult patients with recurrent infections may reveal similar, apparently acquired defects in PMN function.


Gold serum levels in children with juvenile rheumatoid arthritis.

Serum gold levels were monitored in 66 children with juvenile rheumatoid arthritis, treated with different i.m. dosage schedules of sodium aurothiomalate (Myocrisin, Pharma Rhodia). The ages of the children varied from 1 to 15 years. Gold serum levels in children were related to the dose of Myocrisin calculated per kg of body weight or per square metre of body surface area. The results of our study indicate that in order to achieve a peak serum level at about 500--600 microgram/100 ml (25--30 micromol/l) with weekly injections, the dose of Myocrisin should be about 0.7 mg/kg, or 20 mg/m2. In order to avoid excessively high gold serum concentrations, the maximum single dose should not exceed 27 mg/m2 of body surface area.


Comparison of penicillamine and gold treatment in early rheumatoid arthritis.

In a series of 100 adult patients with definite rheumatoid arthritis of at most 3 years' duration and with no previous penicillamine, gold or systemic corticosteroid treatment, 50 patients were treated with D-penicillamine and 50 with gold for one yar. The dose of penicillamine was 600 mg daily. Sodium aurothiomalate was given 50 mg weekly up to a total of 13 mg/kg and thereafter 50 mg once a month. In both treatment groups a statistically significant decrease in the number of painful and/or swollen joints, an increase in haemoglobin and a decrease in ESR, serum ceruloplasmin-, alpha1-acid glycoprotein-, IgG-, IgM- and IgA levels was observed. All the changes in these clinical and laboratory tests were of the same degree in both treatment groups. In the penicillamine group 12 out of 20 seropositive patients became seronegative and in another 5 the Waaler-Rose titre dropped clearly. In the gold group, 7 out of 16 seropositive patients became seronegative, and the Waaler-Rose titre dropped in another 5. An equal increase in the number of eroded joints in hands and toes was seen in the penicillamine and the gold group. Penicillamine was discontinued because of side effects in 13 patients (26%), and gold treatment in 15 (30%). Proteinuria and/or haematuria were the most common causes of discontinuation in the penicillamine group.


Costs and benefits of measles vaccination in Finland.

Measles vaccination is fairly beneficial. During the third year after launching of the vaccination programme, cumulative benefits accuring from vaccination outweigh the cumulative costs of vaccination. This conclusion is based on a study of the vaccination programme in Finland. According to the vaccination programme, all 1-year-old infants in Finland are vaccinated. The duration of the period under survey has been set at 25 years, the measuring unit is the Finnish mark and the price level is that of the year 1975. When comparing costs and benefits, these are converted to present day monetary values. Vaccination costs per vaccinated infant amount to 32 marks, and in total during the period 1975--1999 they will amount to about 34 million marks according to an interest rate of 9% and to about 41 million marks according to an interest rate of 6% in current monetary value. Benefits gained by vaccination, compared with costs, are manifold. The benefits of one vaccination have been estimated at 230 marks. In total, benefits during the period 1975--99 constitute ca 117 million marks at an interest rate of 9%, and ca 159 million marks at an interest rate of 6% in current monetary value, without any deduction for vaccination costs. The net gain of vaccination--with a deduction of vaccination costs--is ca 84 million marks at an interest rate of 9%, and ca 118 million marks at an interest rate of 6% in current monetary value.


Calcium entry leads to inactivation of calcium channel in Paramecium.

Under depolarizing voltage clamp of Paramecium an inward calcium current developed and subsequently relaxed within 10 milliseconds. The relaxation was substantially slowed when most of the extracellular calcium was replaced by either strontium or barium. Evidence is presented that the relaxation is not accounted for by a drop in electromotive force acting on calcium, or by activation of a delayed potassium current. Relaxation of the current must, therefore, result from an inactivation of the calcium channel. This inactivation persisted after a pulse, as manifested by a reduced calcium current during subsequent depolarization. Inactivation was retarded by procedures that reduce net entry of calcium, and was independent of membrane potential. The calcium channel undergoes inactivation as a consequence of calcium entry during depolarization. In this respect, inactivation of the calcium channel departs qualitatively from the behavior described in the Hodgkin-Huxley model of the sodium channel.


Transient synapses in the embryonic primate spinal cord.

Electron microscopic and tritiated thymidine autoradiographic analysis of the embryonic spinal cord in the rhesus monkey reveals considerable rearrangement of cellular and synaptic relationships in the posterior (sensory) quadrant during early developmental stages. This remodeling involves the death of an entire population of neurons that received synapses from sensory afferent axons and the possible relocation of these afferents upon subsequently generated viable substantia gelatinosa neurons.


Primary hypothyroidism and pituitary insufficiency.

A 40-year-old man with primary hypothyroidism and sellar enlargement is described. There was deficiency of all pituitary tropic hormones except TSH which was elevated. TRH stimulation revealed responsiveness of pituitary thyrotropic cells, and thyroxine administration suppressed the elevated TSH. These findings are compatible with either a TSH-producing chromophobe adenoma resulting from primary hypothyroidism or, because of the suppressibility of the TSH secretion, thyrotropic hyperplasia secondary to hypothyroidism maintaining TSH secretion in the face of a non-TSH-secreting pituitary tumor.


Parenteral nutrition.

Parenteral nutrition therapy was born 35 to 40 years ago when the first steps were taken to perform a protein nutrition by the intravenous supply of amino acids in man. Since that time, many efforts have been made to supply adequate amounts of energy intravenously. These efforts have resulted in the two available systems for parenteral nutrition: the lipid-carbohydrate system and the glucose system. The lipid-carbohydrate system, which corresponds to the nutrient content of normal food, may be given either in a peripheral vein or through a central vein catheter. The glucose system is administered through a central venous catheter. Many problems concerning the parenteral nutrition need to be solved and further elucidated. However, our present knowledge and technique in this field are far advanced over earlier methods. Now all patients who cannot take food in adequate amounts orally or enterally may be kept in good nutritional status by parenteral nutrition. In this way it is possible to prevent starvation and its complications in these patients.


Destructive aortic valve endocarditis from Brucella abortus: survival with emergency aortic valve replacement.

Brucella abortus infection of the aortic valve caused acute aortic regurgitation leading to severe left ventricular failure in a 62-year-old man. He made an excellent recovery after emergency aortic valve replacement. This is the third reported case of successful heart valve replacement for Brucella endocarditis and the second such case involving the aortic valve.


Meseclazone, 5-chlorosalicylic acid and acetylsalicylic acid. Comparison of their effects on in vitro and ex vivo platelet aggregation.

Meseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on pletelet aggregation were evaluated in vitro and ex vivo with acetylsalicylic acid (ASA). In vitro, meseclazone and ASA exhibited almost identical inhibitory potency of secondary phase ADP aggregation while 5-CSA was less effective. Moreover, collagen aggregation was inhibited by all three agents: ASA greater than meseclazone greater than 5-CSA. Thrombin-induced aggregation was inhibited to approximately the same extent by 5-CSA and ASA while meseclazone was inactive. The in vitro effects on the release-inducing aggregants were confirmed by ex vivo experiments in rats. These demonstrated that ASA and meseclazone inhibited collagen-induced aggregation 1 and 4 hr after oral administration although ASA was three to four times more active. ASA, but not meseclazone, was still effective 24 hr after administration. Bleeding times in rats 1 and 4 hr following oral administration of meseclazone and ASA were not altered. It is concluded that meseclazone and/or 5-CSA inhibit in vitro and ex vivo platelet aggregation initiated by the release reaction similar to ASA and other non-steroidal anti-inflammatory drugs.


The effects cytochalasin B on the surface morphology of the toad urinary bladder epithelium: a scanning electron microscopic study.

Cytochalasin B depresses the hydroosmotic response of the toad urinary bladder to vasopressin without affecting basal (bulk flow) permeability, diffusional permeability, or the hormone induced increase in short circuit current. Fine structural studies demonstrated that this macrolide fungal metabolite, in the presence of both an osmotic gradient and vasopressin, induces the formation of large intracellular vacuoles or 'lakes' in epitelial cells lining the bladder mucosa. Some surface changes (shortening and irregularity of microvilli, clumping of the glycocalyx, etc.) were reported by transmission electron microscopy. Scanning electron microscopy demonstrates that cytochalasin B drastically alters the mucosal surface morphology of the hormone stimulated bladder. Lesser changes were seen in the absence of vasopressin. In the presence of arginine vasopressin, excessive cellular swelling and possible rupturing, as well as surface membrane infolding and rippling, were seen in the cytochalasin treated tissues, The specific entity most affected by this treatment is the granular cell.


Ovarian estradiol secretion during early pregnancy in monkeys: luteal versus extra-luteal secretion and effect of chorionic gonadotropin.

To determine the locus of ovarian estradiol secretion during early pregnancy, six monkeys were luteectomized (CLx) on days 22 to 24 of pregnancy. Daily peripheral serum concentrations of progesterone were maintained or slightly elevated despite removal of the corpus luteum (CL), while serum estradiol concentrations fell precipitiously (P less than 0.05). It is concluded that the CL of early pregnancy in these monkeys is the primary source of serum estradiol, but that ovarian tissues other than the primary luteal body secrete estradiol at low levels. Further, preliminary results suggest that mCG may be an important stimulus of ovarian estrogen secretion, by both luteal and extra-luteal compartments, in these primates. MCG may stimulate the CL to sustain estradiol secretion even after luteal cells are no longer responsive to this endogenous gonadotropin as regards progesterone secretion.


The Montgomery lecture, 1977. Curious colobomata.

The humble coloboma has been taken as a model in an attempt to illustrate the benefit of continued observation and the application of increasingly sophisticated methods of investigation in the genetic and biochemical areas. The recent literature is reviewed with particular reference to publications dealing with colobomata and systemic malformations. Polycystic renal disease has been produced in animals and the application of the method used to a study of the eye may help to explain some of the unusual systemic clinical combinations which may occur in human cases. A simple factor may yet emerge to account for these anomalies rather than the multifactorial explanations previously postulated.


The activity of serum ribonuclease in protein-energy malnutrition.

Serum alkaline ribonuclease activity and serum albumin concentration were determined in 25 normal children and 59 children with protein-energy malnutrition. The increase in serum ribonuclease was marked in marasmus and marasmic kwashiorkor. The ribonuclease activity dropped significantly after two weeks of treatment and returned to normal by four weeks. In kwashiorkor, serum ribonuclease activity was significantly lower than control and returned to normal after four weeks of treatment. These findings support previous observations that the serum ribonuclease is a good criterion of the nutritional status and indicates that the enzyme activity, particularly when related to serum albumin, is a good prognostic index in this respect.


Treatment of schistosomiasis. Factors affecting chemotherapy and reflections on ideal drug treatment.

The blood concentration of certain known schistosomicides or their active metabolites never reaches levels high enough to prove lethal to the parasite. The chemotherapeutic response is a function of the relations of the triad-drug, parasite and host. This article reviews the multiple factors which influence the chemotherapeutic response in schistosomiasis with references to researchers in this wide field. An understanding of these complex interactions is a basis for the design of drug trials in the search for the ideal schistosomicide.


Waldenström's macroglobulinaemia in South African Negroes.

Waldenström's or primary macroglobulinaemia has rarely been documented in Black Africans. Six South African Negro patients with Waldenströms macroglobulinaemia were assessed and followed during a 10-year period from 1966 to 1976. The hyperviscosity syndrome was the presenting feature in four patients and one patient each presented with the nephrotic syndrome and a lacrimal mass respectively. On initial evaluation of the six patients, the serum IgM varied from 1.3 to 4.8 g% and in two patients cryoglobulinaemia was found. The patients received supportive treatment, chemotherapy, and when necessary, plasmaphoresis. One patient was lost to follow-up, one patient died 7 years after the onset of his illness, but the remaining four patients are alive 18 months to 5 years after presenting with their disease. Although the disease occurred in a younger age group (mean age 43 years) than in Caucasians it did not differ in clinical features or response to treatment from other parts of the world.


The incidence of theilerial parasites in East African buffalo (Syncerus caffer).

245 buffalo from 13 areas of East Africa were examined for theilerial infections. The vast majority of buffalo (97.1%) examined had piroplasms in their erythrocytes. Theileria lawrencei was isolated from the buffalo by tick feeding and cell culture and was found to be common in most of these buffalo populations. Also over 50% of the buffalo had indirect fluorescent antibody (IFA) titres to T. lawrencei. T. mutans was only isolated from 3 buffalo populations but is probably common. Haematoxenus sp. was detected in the blood of 56% of the buffalo sampled. In the light of these results the role of buffalo as a reservoir of cattle pathogenic theilerioses in East Africa is discussed.


Ultrastructural study of Sarcocystis fusiformis (Railliet, 1897) infecting the Indian water buffalo (Bubalus bubalis) of Egypt.

Sarcocysts from the muscular layer of the oesophagus of 20 Indian water buffaloes (about 7--10 years old) have been collected in Egypt and studied by means of electron microscopy in Bonn (West Germany). Large and small cysts have been observed. The large type ranged from 7--30 X 3--7 mm, and the small cysts measured 1.3--5.1 X 0.7--2.2 mm. The metrocytes of both types of cysts as well as the merozoites were very similar concerning their shape, size and ultrastructural characteristics. The metrocytes of the large and small cysts were mostly located at the peripheral region of the cysts and multiplied by endodyogeny. They were variable in shape and size. They ranged from 7.6 X 4.8 micrometer to 9.2 X 5.4 micrometer. Most of them exhibited deep invaginations of their pellicle. Their cytoplasm was electron pale and often extremely vacuolated. The merozoites of both types of cysts were elongated with a length ranging from 14.6--17.0 micrometer and showed all characteristic organelles of these cells (conoid, rhoptries, micronemes, subpellicular microtubules etc.) The wall of the large and small cysts showed no distinct morphological differences. The great similarities between the walls of the two types of cysts as well as between the micromorphology of the developmental stages (metrocytes and merozoites) lead to the conclusion that the two types of cysts examined may belong to one species of Sarcocystis.


Catabolism of adenosine 5'-monophosphate in promastigotes of Leishmania tropica.

The specific activities of enzymes participating in AMP-catabolizing reactions in promastigotes of Leishmania tropica were determined. The following sequence of reactions is suggested: AMP leads to adenosine leads to adenine leads to hypoxanthine. The initial enzyme of this sequence, AMP nucleotidase, is apparently membrane-bound. The significance of AMP catabolism with respect to adenylate energy charge and a signal transfering mechanism is discussed. Adenine deaminase has been partially purified and characterized. Several purine analogues, inter alia allopurinol, proved to be inhibitors of the adenine deaminase catalyzed reaction.


Histopathology of experimental Chagas disease in NMRI-mice. A long term study following paw infection.

NMRI-mice were infected subcutaneously with T. cruzi Brazil and the pathohistological findings in 17 organs at different times after infection are described. The paw was chosen as injection site, for, due to the great variety of tissues found in a single histological section, the first reactions between host and parasite are best studied here. For this purpose the complete paw was embedded in plastic and sectioned longitudinally. After infection with 5 X 10(4) parasites a shift of parasitism from the initial host cells (macrophages) to the neighbouring muscle cells was observed. This occurred on the 9th day after infection. On the 18th day a generalized parasitism of organs containing muscle had developed, especially of myocardium and alimentary tract. Destruction and inflammation of heart muscle was the most important consequence with respect to mortality. The autonomous nervous system of heart and alimentary tract was involved, although not selectively. Liver and spleen played no role as host tissues. After infection with 10(2) or 10(3) parasites specific alterations in the animals surviving the acute phase were not observed from the 60th to 201st day. A perivenous encephalitis without cerebral parasitism was found in about one half of the experimental animals. It does not correspond to the known 'Chagas encephalitis' and is for the present defined as parainfectious.


[Effect of substances that disrupt cell adhesion to the substrate on the glycoprotein spectrum of normal fibroblasts in culture].

Alterations of glycoproteins pattern of normal mouse and chick embryo fibroblasts, caused by chemicals impairing cell-substrate adhesion were studied in culture. The chemicals used were proteases (trysin, pronase and papain), EDTA and urea. Using sodium dodecyl sulfat polyacrylamide gel electrophoresis, it was shown that mouse fibroblasts contained four major high-molecular mass glycoproteins that were removed from cells when the adhesion was impaired. Their apparent molecular masses were estimated to be 268 000 (GP-268), 260 000 (GP-260), 211 000 (GP-211) and 196 000 (GP-196). Each glycoprotein proved to be senitive only to one treatment: GP-268 - to very low doses of proteases (1--10 microgram/ml, 10 min), GP-260 - to long treatment with urea (1 M, 2h), GP-211 and GP-196 - to cell rounding and detachment from the substrate caused by long treatment with EDTA (200 microgram/ml, 30 min). In contrast to mouse cells, chick fibroblasts contained only one major high-molecular mass glycoprotein with an apparent molecular mass 266 000 (GP-266) sensitive to all the treatments tested, but to a different degree. The role of glycoproteins studied in the process of cell-substrate adhesion as well as the dependence of certain glycoproteins (GP-211 and GP-196) on the cell shape is discussed.


[Electron microscopic study of the nuclei of Euglena gracilis].

The ultrastructure of the Euglena gracilis nucleus has been studied with electron microscopy and prefential staining of ribonucleoproteins. The interphase nucleus chromatin is mainly concentrated in chromonemata - i.e. elongated threads of condensed chromatin. Part of them is directed to the nuclear envelope, with which they are in contact. The number of these contacts is approximately equal to the chromosome number. The Euglena gracilis nucleoplasm is rich in various RNP-components, which points to the transcriptional activity of chromatin, although the majority of chromatin is condensed.


Integrated therapy for invasive bladder carcinoma. Experience with 108 patients.

One hundred eight patients with invasive bladder carcinoma, clinically staged T3, who underwent preoperative irradiation followed by radical cystectomy and ileal conduit urinary diversion without pelvic lymphadenectomy at this Center between January 1, 1969, and December 30, 1975, were reviewed. Sixty-two patients are alive and free of disease twelve to ninety-six months after treatment. The incidence of recurrent pelvic disease is 8%. With protracted radiotherapy (5,000 rads TD/five weeks), pelvic lymphadenectomy is not necessary and has the benefit of distinguishing high-risk population who may benefit from adjuvant therapy.


Experimental acute renal failure in primates. Clinical and histopathologic evaluation in light and electron microscopy.

Acute renal failure or its equivalent, acute tubular necrosis, was induced in rhesus monkeys by a combination of dehydration, hemorrhagic hypovolemia, and packed cell transfusion. Clinicopathologic changes were studied at different time intervals. Increasing edematous swelling and disintegration of the epithelial cells in the convoluted tubules, thick loops of Henle, and collecting tubules during the first four hours were conspicuous. As a result, intratubular cellular detritus, red blood cells, and various types of casts were increased progressively between one and four hours, and decreased thereafter. As the time progressed, edema was subsiding but the absorption granules and fat droplets were increased in size and number from one to twenty-four hours. These findings would indicate widespread cellular degeneration and necrosis. Consequently, tubular integrity was impaired leading to necrosis, denuded tubular basement membranes, and occasional tubulorrhexis. Concurrently, some dilated peritubular or interstitial capillaries were ruptured releasing red blood cells and cellular debris, which eventually were picked up by the damaged tubules. Although the regeneration of the renal parenchyma was in progress after sixteen hours, groups of subcapsular tubules were dilated showing flattened epithelial cells. The glomerular capillaries were either dilated or engorged, empty or collapsed during the experiment. Bowman's spaces contained red blood cells and varying amounts of cellular debris. Although the clinicopathologic changes reported here may be attributed to one or more of the following factors, hypoxia, toxic effects and dehydration, most of the changes were apparently due to hypoxia.


[Properties of adenylate cyclase of rabbit skeletal muscle sarcolemma].

The sarcolemma fraction with a considerable adenylate cyclase activity sensitive to adrenalin is isolated from the rabbit skeletal muscles. Some its properties are established: pH-optimum of the activity, stability in storage and resistance to the effect of different pH and temperature. Acetylcholine and ruthenium red do not affect the adenylate cyclase activity of the sarcolemma. EGTA activates and Ca2+ inhibits it having no effect on sensitivity to adrenalin.


[Microbial contamination of dust in minimum-morbidity housings for pig rearing].

The range of the microbial contamination of 1 g of dust in minimum-morbidity pig rearing houses is from 2.9 . 10(7) to 7.6 . 10(9) in the microbes growing on meat-peptone agar (MPA), from 4.6 . 10(7) to 4.6 . 10(8) in moulds growing on the Czapek-Dox agar, from 1.4 . 10(2) to 7.0 . 10(4) in the total number of microbes growing on End's agar, and from 3.1 . 10(2) to 5.7 . 10(3) in the typically lactose-positive microbes growing on End's agar. The numbers of microbes in 1 g of dust in the conventional pig houses are close to the numbers found in pig rearing houses with minimum morbidity. However, in the moulds on the Czapek-Dox agar, the range of the microbial contamination of dust in the minimum-morbidity pig houses was much higher. The highest level of the contamination of dust with microbes was found on all types of media from houses with continual operation. It was revealed by the control of the effectiveness of disinfection in the minimum-morbidity piglet rearing section, operated on the all-in all-out basis, that in a half of the cases studied the disinfection had low effectiveness. The total number of microbes per 1 sq. cm was lower than required on the basis of research published in literature, but the occurrence rate of positive smears with lactose-positive microbes after disinfection was higher in percentual expression.


[Induction of labor and its synchronization in hogs].

The authors describe the synchronization of farrowing by the induction of parturition with a prostaglandin F2alpha analogue (Cloprostenol). The time sequence of the beginning of parturitions was recorded in 147 sows after administration of 175 microgram Cloprostenol. 93.7% of the parturitions take place between the 14th and 39th hour after administration, the peak time being between the 24th and 27th hour (31.2%). The schedule of the farrowing days is described as a prerequisite for a qualitative change in the organization of work in large pig herds.


[Agglutination and acrosome reaction of ram spermatozoa incubated in the bovine folicular fluid].

Fresh-ejaculated sperm of ram was incubated at a temperature of 38 degrees C in the bovine follicular fluid and homologous blood serum (blood plasma). The spermatozoa were studied in native state under a microscope with phase contrast and as ultra-thin sections under a transmission electron microscope. In the follicular fluid and in the blood serum, strong agglutination of spermatozoa occurred, with its maximum after about two hours. Only the heads of spermatozoa agglutinated, the flagella being loose were arranged parallelly. Although the progressive motility of spermatozoa was not observed, the motility of flagella was not affected. The investigation under the electron microscope showed that the agglutination occurred only in acrosomes of intact spermatozoa. It was also found out that the follicular fluid induced the acrosome reaction of spermatozoa. The course of the acrosome reaction is similar to that in the other mammals: first of all plasma membrane becomes undulated, then it fuses with the outer acrosome membrane, giving origin to vesicles within the entire acrosome, except the equatorial segment. The acrosome reaction was found in about 5% spermatozoa, and therefore it may be assumed that secretions of the oviduct and uterus play their role to induce the acrosome reaction.


[The effect of the antidiuretic hormone on the renal excretion of urea and electrolytes in fed and fasting sheep].

The effects of the antidiuretic hormone (ADH) on the renal excretion of urea and electrolytes were studied in sheep, subjected to water stress, before and after 36-hour fasting. The intravenous administration of synthetic lysine-vasopressin (L-VP) at the dose of 100 microgram per kg induced only a temporary, statistically insignificant, drop of the urinary urea outputs by the fed as well as fasting sheep. L-VP did not influence the excretion of sodium and potassium electrolytes either. It follows from the results that there are no differences in the renal response to ADH between the fed sheep and sheep that have fasted for 36 hours.


[Diagnosis of infectious anemia in horses using the Coggins test].

Coggins' immune diffusion test was modified, and was applied as a screening one in the study of the epizootic status. The positive reactions were characterized by the production of a precipitation line between the antigen and the respective serum that was tested. The appearance of such a line was associated with that formed with the use of the positive control serum, pointing to a reaction of identity. With the weakly positive reactions the ends of the precipitin lines, formed with the use of the positive control serum, were found to deviate slightly toward the site where the antigen had been placed. The specificity of the test was confirmed through biological experiments and clinical, morphological, and hematological investigations.


Ultrastructural nuclear changes in human lymphocytes following arabinosylcytosine treatment in vitro.

Human lymphocytes were separated by centrifugation and grown for 48--72 h in TC 199 medium. Synchronous cells, obtained by the addition of colchicine, were treated with arabinosylcytosine (Ara-C), an antimitotic substance which is known to produce nuclear changes in vivo and in vitro. In this case, alterations in the nuclear envelope closely resembling the malignancy associated changes described in human leukaemic cells were observed. The results allow us to suggest that such alterations may be due to a cellular derangement involving the renewal of the nuclear envelope in th G1 phase of the mitotic cycle.


A scanning electron microscopic study of rat Masugi nephritis.

Changes in the glomerular capillaries in the first phase of rat Masugi nephritis were studied by scanning electron microscopy. The changes developed immediately after the injection of nephrotoxic rabbit IgG and early endothelial lesions (2 to 6 h) were characterized by an increase in microvilli and a decrease in endothelial pores. The microvilli were fused and produced abundant pored projections (cytofolds). The peripheral endothelium was then lifted off from the glomerular basement membrane (GBM), leaving scattered endothelial fragments on the GBM. The denuded GBM exhibited a rather uniform, thick carpet-like appearance with occasional crater formation. Depositon of fibrin strands was seen associated with endothelial exfoliation. These later dissolved and were converted to a fibrinoid material, consisting of a complex of fragmented, thin fibrils. A parallel study using the electron microscope revealed that the fibrinoid material was removed by emigrating monocytic macrophages. At the stage of resolution (24 to 72 h), the denuded GBM was covered mostly with a regenerating endothelial layer. A possible process of reorganization of the endothelial pores is discussed.


An ultrastructural investigation of nephrotoxicity in rats induced by feeding cultures of Penicillium verrucosum var. cyclopium.

A renal tubular lesion was induced in male rats by giving them a culture homogenate or culture filtrate of Penicillium verrucosum var. cyclopium by gastric gavage for 20 days. The fungus was obtained from stored maize in an area of endemic nephropathy in Bulgaria. Changes in the proximal convoluted tubules were studied by light and electron microscopy. The lesion was confined to the pars recta in the outer stripe of the outer zone of the medulla. It consisted of degeneration and necrosis of epithelial cells, prominent karyomegaly, arrested mitotic divisions and production of binucleate and tetranucleate tubular cells. Two patterns of degeneration occurred with comparable frequency: a vesicular form with pyknotic nucleus and electron lucent degeneration. Nuclei of the epithelial cells in affected tubules contained segregated nucleoli. The necrotic cells were replaced by actively regenerating cells derived from adjacent viable epithelium. The similarity between the tubular lesions induced in rats and the changes found in patients with Balkan endemic nephropathy is discussed.


The effect of single and of multiple doses of prednisolone tertiary butyl acetate on cell population kinetics in the small bowel mucosa of the rat.

The effect of single and of multiple doses of prednisolone upon cell population kinetics in the rat jejunal crypt was investigated, using autoradiography and stathmokinetic techniques with vincristine. Single injections of prednisolone (2.5 mg/kg body weight) induced a depression both flash thymidine labelling and mitotic indices; this change was shown to be due to a decreased cell production rate. Recovery of these proliferative indices occurred over seven days after injection; measurement of crypt size parameters showed a transient decrease in crypt population. Multiple daily injections of prednisolone (1 mg/kg body weight) produced a more sustained decrease in labelling and mitotic indices, which lasted as long as injections were continued (7 days); stathmokinetic techniques showed decreases in cell production rates, and the crypt population was also depressed throughout this period. It is concluded that prednisolone depresses cell proliferative rates in rat jejunal mucosa.


Cell junctions in dyserythropoiesis.

Erythroid cell junctions have previously been reported in some cases of dyserythropoietic anaemia. This study has demonstrated that they are a relatively common occurrence in dyserythropoiesis. They range from apposition of cellular membranes with preservation of the intercellular space, to membrane confluence, to interdigitation and septate-like junctions. By special staining with colloidal lanthanum, ruthenium red and tannic acid, together with studies of the effect of proteolytic enzymes, their structural composition has been identified and it was confirmed that they are not artefact. The role of cell junctions in dyserythropoiesis is discussed.


Cytogenetics in malignant lymphoma.

There appear to be four primary areas of interest in the application of cytogenetic techniques to the study of malignant lymphomas: (1) the role of cytogenetics in the diagnosis of lymphoma in problem cases, (2) as an aid to the classification of malignant lymphomas, (3) whether specific chromosomal patterns will have prognostic significance for response to therapy or survival, and (4) the role of cytogenetics in staging of malignant lymphomas. A case of reactive lymphoid hyperplasia is reported in which cytogenetic studies demonstrated an aneuploid clone suggesting that cytogenetic abnormalities of lymphoma may precede the diagnostic histopathologic picture. The occurrence of 14q+ marker chromosomes in plasmacytic myeloma, plasma cell leukemia, malignant lymphomas, Burkitt's lymphoma, and ataxia-telangiectasia suggest that a common etiologic or pathogenetic mechanism may be present in some of these disorders. A preliminary pilot study of spleens removed at staging laparotomy for Hdgkin's disease suggests that cytogenetic studies may be able to detect Hodgkin's disease that is not apparent histologically. Further studies are required to provide answers to these areas of interest in cytogenetics in malignant lymphoma.


Hairy cell leukemia: an analysis of the chromosomes of 26 patients.

We studied the chromosomes from 26 patients with hairy cell leukemia (HCL) to ascertain the frequency and types of consistent chromosomal abnormalities. Samples from 21 patients were obtained from peripheral blood cultures grown 24 and 48 h without phytohemagglutinin, or from bone marrow samples. Two male patients had similar, consistent abnormalities; one patient's karyotype was 46, X, +12; that of the second was 46, X, +C marker. In the latter case, the distal long arm of the C marker most closely resembled chromosome No. 12 from band q14 to q terminal, but the short arm and proximal long arm were of undetermined origin. Both karyotypes lacked the Y chromosome. Nine of the 21 patients had abnormalities in single cells. One patient had, in one sample, a single abnormal cell with an extra No. 3 and an extra No. 12 (48, XY, +3, +12), and in a later sample, a second cell of poor morphology which also could have been trisomic for No. 12. Another patient had one cell with an unusually bright short arm, as well as two cells, with different abnormalities, both involving the short arm of chromosome No. 1. The two patients with consistent chromosome abnormalities had rapidly progressive disease in spite of splenectomy, and their clinical course from the time of diagnosis was relatively short (5 and 7 months, respectively).


Cytogenetics of chronic T cell leukemia, including two patients with a 14q+ translocation.

Chromosome studies were done on 7 patients with chronic T cell leukemia. Their lymphocytes responded in culture to one or more T cell mitogens: PHA, Con A, or the calcium ionophore A23187. Clones of cytogenetically-abnormal cells were present in all seven patients, but on occasion the frequency of such cells varied greatly in cultures stimulated with different mitogens. There was no consistent chromosome change, but alterations of chromosome 2 were noted in four individuals and of chromosome 14 in three. In two patients, there was a translocation to the long arm of chromosome 14, producing a 14q+, with the break point in the terminal portion, an abnormality previously observed in B cell lymphomas. One of these patients also showed evidence of clonal evolution in sequential cytogenetic studies, but more data are needed to determine whether such investigations are of prognostic value with respect to the clinical course of the disease.


Chromosomes in solid tumors.

Systematic chromosomal studies in solid tumors have been scanty (excepting meningiomas), because of the fact that it is difficult to obtain tumor material at desired times and only in about 10--15% of the cases adequate chromosome preparations are suitable with a direct technique or short term culture. A few facts that emerge from the study of various solid tumors are as follows: 1. modal number of chromosomes in parimary tumors tends to be lower that of metastatic; 2. certain chromosomes and chromosome regions are more susceptible for breakage to oncogenic conditions, hence, there is non-random involvement of certain chromosomes in human neoplasia and 3. certain chromosome changes are more often associated with metastatic spread than others.


Abnormalities of chromosome No. 1: significance in malignant transformation.

Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.


Tumors as clonal proliferation.

Cytogenetic studies indicate that most tumors are clonal (i.e. unicellular in origin) and have karyotypic alterations. These are not consistent, but non-random abnormalities are being increasingly identified by banding techniques, pointing to the sites on human chromosomes where genes important in neoplastic development are located. It is postulated that tumor progression occurs as a result of genetic lability within the neoplastic clone, leading to emergence of increasingly mutant subpopulations (often recognizable cytogenetically) with more malignant properties. In the context of this hypothesis, acute leukemia, chronic leukemia, and preleukemia can be viewed as differing only in the rate at which an abnormal hemic clone is expanding, with progression to a more aggressive phase (e.g. the "blast crisis" of chronic granulocytic leukemia) reflecting emergence of a new predominant subpopulation as the result of an additional genetic change. These concepts, and the cytogenetic data from which they have been derived, may help our understanding of basic tumor biology, and have some practical applications in the diagnosis of human neoplasms.


Some comments regarding chromosome pulverization (premature chromosome condensation or PCC, prophasing).

Premature chromosome pulverization (PCC) or prophasing is a much misunderstood cytological entity. It must be separated from chromosome damage caused by a number of chemical, physical and biological agents. Prophasing is observed in fused cells in which one of the constituent cells must be in metaphase and another in interphase. The morphology of the "pulverized" interphase nucleus will depend on the phase of the cell cycle in which the interphase cell was in when exposed to a substance present in the cytoplasm of the metaphase cell leading to "prophasing". Prophasing is a normal cellular phenomenon occurring prematurely or under abnormal conditions (fusion of cells) and its demonstration in human cells or tumors may be indicative of the presence of a virus (or its products) which leads to cell fusion, but does not play a role in prophasing.


Preleukemic syndromes.

Acute nonlymphocytic leukemia (ANLL) is preceded by a hematologic illness representing the "preclinical" stages of the disease in many patients. This "preclinical stage" or preleukemic stage is difficult to recognize by conventional hematologic morphologic techniques. A prospective study was carried out to determine whether cytogenetic studies would be helpful in the recognition of preleukemic states and whether the presence of cytogenetic abnormalities would have prognostic significance. A study of 284 patients with suspected preleukemia has yielded 62 patients with progression to overt ANLL. Cytogenetic abnormalities were found in 30% of suspected preleukemic patients, whereas 53% of the patients progressing to acute leukemia had cytogenetic abnormalities. These studies show that the presence of cytogenetic abnormalities aid in the recognition of preleukemia but are not specific for early leukemia. Patients with cytogenetic abnormalities are more likely to develop overt ANLL. Banded chromosome studies demonstrated cytogenetic abnormalities in the preleukemic phase in 13 of 26 patients. A variety of clonal chromosomal abnormalities were observed.


Chromosome studies in polycythemia vera.

Polycythemia vera (PV) represents an apparent monoclonal stem cell proliferation with a frequent transition to full neoplastic behavior. Up to 26% of untreated PV patients can be expected to have some chromosome abnormalities in the marrow at the time of diagnosis, and 10--15% have an abnormal cell line or clone. Both structural and numerical aberrations occur. Aneuploidy is the most common type of chromosome abnormality, however, with hyperdiploid clones occurring more frequently than hypodiploid clones. Chromosomes 1, 8, 9 and 20 are involved in a non-random pattern, and aberrations of all the F group, or at least the No. 20 chromosome seem to be associated to some extent with diseases involving erythroid hyperplasia. Leukemia develops in a certain percentage of patients regardless of the type of treatment they have received, but the relationship, if any, between the chromosome abnormalities and the development of leukemia is still uncertain. The abnormal clones that occur in PV appear to be quite stable and there is no indication at this time that they correlate with a prognosis of leukemic transformation.


Cytogenetics of acute and chronic myelofibrosis.

In myelofibrosis, acute or chronic, as well as in other myeloproliferative disorders which carry an increased risk of developing leukemia, a clone of hemic cells with a chromosome abnormality is a relatively common occurrence. To date, however, the presence or absence of a cytogenetic alteration has not been of prognostic value with respect to subsequent clinical course. No particular karyotypic change is specific for myelofibrosis, but many of the same non-random abnormalities occur as in other leukemic and preleukemic states. Both cytogenetic and isoenzyme data indicate that the fibrous tissue in the marrow is not part of the myeloproliferative clone.


Cytogenetic patterns in acute nonlymphocytic leukemia.

Analysis of chromosomal banding patterns in acute nonlymphocytic leukemia (ANLL) reveals that approximately 50% of patients have an abnormal karyotype. Although there is substantial variability, certain nonrandom abnormalities occur, e.g., +8, -7, and the 8;21 translocation (often accompanied by loss of an X or Y chromosome). The 15;17 translocation appears to be highly specific for acute promyelocytic leukemia. These abnormalities usually are not seen in remission, but reappear in relapse, sometimes exhibiting further clonal evolution; a +8 is the most frequently observed evolutionary change. Patients with ANLL following treatment of a malignant lymphoma tend to have hypodiploid modal numbers and frequently show loss of a chromosome No. 5 or No. 7.


Clinical implications of chromosome abnormalities in acute non-lymphocytic leukemia: current status.

Data currently available on banded chromosome studies on patients with ANLL suggest that the presence of a chromosome abnormality in such patients indicates a poor prognosis, and that different treatment strategies need to be developed for these patients. However, patients with at least one normal metaphase survive nearly as long as those with only normal metaphases. A specific chromosome abnormality in APL [t(15;17)], an unusual association of a translocation [t(8;21)] in association with loss of a sex chromosome, and a rare association of thrombocytosis and a chromosome insertion (3;3 ins), suggest that some chromosome changes in ANLL are specific.


The Philadelphia chromosome in acute leukemia.

The cytogenetics, cytology and cytochemistry, clinical findings, therapeutic response and survival of patients presenting with acute leukemia and the Philadelphia chromosome (Ph1) are briefly reviewed based upon a survey of the world literature and 16 cases seen at the University of Minnesota during the last 10 years. Details regarding the 16 cases from the University of Minnesota series are presented and two appendices listing the majority of reports of Ph1 + acute leukemia are included. Comparison of adults with Ph1+ and Ph1- acute leukemia demonstrate important clinical, therapeutic and prognostic differences. In general, patients with Ph1+ acute leukemia respond less well to treatment and survive significantly shorter periods of time. Since the presence of the Philadelphia chromosome in acute leukemia has therapeutic and prognostic significance, marrow chromosome studies should be performed in adults presenting with acute leukemia, especially acute lymphocytic leukemia.


Chromosome studies in myelomatosis.

Cytogenetic studies of patients with multiple myeloma and plasma cell leukemia have shown that chromosome abnormalities occur in the bone marrow and/or the PHA-stimulated blood of at least half the patients. The abnormalities include numerical and structural aberrations and are highly variable. Hypodiploid modes occur fairly frequently. Addition of material to the long arm of the No. 14 chromosome (14q+ marker) occurs in about 17% of the small series of patients that have been studied with banding so far.


Significance of 14q translocations in non-Hodgkin lymphomas.

Chromosome studies were performed on malignant cells obtained from 22 patients with non-Hodgkin lymphomas. A marker chromosome resulting from a translocation that affected the long arm of No. 14 (14q+) was the single most frequent abnormality and was noted in 14 of these patients. The frequency of the 14q+ marker chromosome varied with the type of lymphoma as defined by Rappaport. When the Lukes and Collins classification was used, the 14q+ marker was consistently associated with lymphomas having a clone of large noncleaved cells, small cleaved cells, and small noncleaved cells, but was absent in lymphomas composed of a clone of large cleaved cells and small lymphocytes. The findings suggest that, in certain groups of lymphoid malignancies, cells with a 14q translocation have a proliferative advantage compared with cells having other chromosome rearrangements, and that these malignant cells could be derived from a common progenitor.


Sulphur-containing metabolites of beta-bromostyrene formed by the marmoset, rabbit and rat.

1. The administration of beta-bromostyrene to the rat results in a fall in the level of hepatic glutathione. 2. Marmosets, rabbits and rats dosed with beta-bromostyrene excrete two mercapturic acids. One of these, N-acetyl-S-(2-hydroxy-2-phenyl-1-bromoethyl)-cysteine is readily converted into N-acetyl-S-(1-phenyl-2-bromo-2-ethenyl)-cysteine, the structure of which was established by mass spectrometry. 3. Mass spectrometric evidence suggests that the second mercapturic acid is N-acetyl-S-(1-hydroxy-2-phenylethyl)cysteine. 4. Mandelic acid was detected as a metabolite in all three species.


The disposition and metabolism of flurbiprofen in several species including man.

Flurbiprofen was rapidly absorbed in all species studied. 2. Half-lives of elimination measured 0 to 12 h after a single dose were: mouse 3.4 h, rat 2.5 h, dog 10.1 h, baboon 3.1 h and man 3.9 h. A second phase of elimination was seen in the dog. Flurbiprofen accumulated in the circulation of the dog on repeated dosing. 3. After dosing with [14C]flurbiprofen, tissue levels of radioactivity in dog and baboon were similar to that in plasma. In the rat, levels were slightly elevated in liver, kidney, large intestine and thyroid after repeated dosing. 4. The dog excreted equal amounts of radioactivity in urine and faeces. In other species renal excretion was the more important route. 5. Six metabolites have been detected, the most important being: 2-(2-fluoro-4'-hydroxy-4-biphenylyl)propionic acid (metabolite 1), 2-(i-fluoro-3',4'-dihydroxy-4-biphenylyl)propionic acid (metabolite 2) and 2-(2-fluoro-3'-hydroxy-4'-methoxy-4-biphenylyl)propionic acid (metabolite 3). The proportions of the metabolites and the extents of their conjugation varied among the species. 6. Metabolites were detected in the circulation of rat, mouse and baboon but not in dog and man. 7. Flurbiprofen did not affect the hepatic drug-metabolizing enzyme system of rat. 8. Flurbiprofen was extensively bound to serum protein of rat, dog, baboon and man.


Effects of crops on the humus accumulation process in the grey forest soils of Priangarye.

The influence of a number of agricultural plants in the crop rotation on the grey forest soils in the Irkutsk Region upon the intensity of the humification process was investigated by means of microbiological and biochemical tests. The synthesis, decomposition, and the accumulation ratio of humus were concluded from the phenoloxidase activity. The cellulose-decomposing microflora and algaeflora were taken into consideration as well. The humus synthesis processes were most active in the wheat and lucerne plots, they were less effective in the fallow and virgin soils. The lack of organic matter in the permanent fallow soil cuts down the humus accumulation ratio and the counts of microorganisms. The soil cultivation intensifies the humus synthesis processes and changes the composition of microorganisms in the soil. Algae which are mainly represented by green and blue-green species are an additional source of organic substance in the soil. Decomposition of organic substances in the soil proceeds with an active participation of cellulose decomposers which are mainly represented by fungal and bacterial flora. In rare cases actinomycetes can be found. Application of mineral fertilizers intensifies the humus accumulation process and improves the qualitative and quantitative composition of microflora in all the plots under investigation.


Mechanism of action of bilharcid and tartar-emetic.

An investigation on the mechanism of action of bilharcid and tartar-emetic produced the following results. Deoxyribonucleic acid (DNA) synthesis by cell of E. coli B from either the maximum stationary phase or the exponential phase are inhibited by 3.62 mM of bilharcid or 16.81 mM of tartar-emetic immediately upon addition of the inhibitor. These drugs cause a downshift of the Tm of native DNA. They displace MG from the DNA-MG complex. They increase the specific viscosity of DNA solution. Also the synthesis of constitutive enzyme (alkaline phosphatase) was stopped, as was the induction of the synthesis of new enzyme (beta-galactosidase). Bilharcid and tartar-emetic act primarily on cell membrane and cause the release of 260 mM absorbing substances from E. coli B. Moreover, they lyse not only protoplasts of B. subtilis, but also spheroplasts of E. coli B.


[Post partum rubella vaccination and anti-D prevention].

The effectiveness of a routinely performed puerperal rubella vaccination was tested. Additional a possible adverse influence of simultaneously administered anti-D immunoglobulin on the effectiveness of the rubella vaccination was examined. Rubella antibody titers (HHT) in pregnant women were determined; after delivery puerperal women with titers of less or equal 1:16 were selected for rubella vaccination. 2 1/2 to 3 months later rubella antibody titers were done again. 15% of 130 vaccinated women did not show a conversion of the former negative titer or a low titer of 1:8 remained. Also reductions of the antibody titers were seen. When simultaneously rubella vaccination and anti-D immunoglobulin was administered only in 1 case out of 27 patients a negative titer remained after vaccination. The used anti-D immunoglobulin contained rubella antibodies of a titer 1:256 to 1:512; according to experimental studies, this concentration should not have any influence to the immunologic response of rubella vaccination. Our practic results could not confirm the reservations concerning simultaneous rubella vaccination and anti-D prophylaxis.


[Light and electron microscopic studies to the development of muscle cysts of Sarcocystis suicanis in experimentally infected pigs (author's transl)].

Six young pigs were experimentally infected with 100000 sporocysts of Sarcocystis suicanis and killed on the 32nd, 47th, 55th, 64th, 81th and 90th day p.i. The ultrastructure of sarcocysts in the muscle cells was studied. Light microscopical preliminary examination on the 32nd day p.i. showed cysts which lay in muscle fibres and were surrounded by a fine membran. On the 55th day p.i. the cyst wall showed radial light and dark stripes of 2.6 micrometer thickness, which reached a thickness of 3.2 micrometer on the 90th day p.i. The electron microscopic study of the cyst wall on the 32nd day p.i. showed a unit membran the numerous small outward projections of which are underlined by osmiophilic material that is absent in the inwardly directed invaginations. During the growth of the cyst, this primary cyst wall became regularly folded, forming many protrusions on the 55th day p.i. These appeared palisade-like and contained 57--62 filamentous elements in a single layer under the primary wall at a distance of 10 nm. In the centre of the protrusions there were 5--8 groups, comprising 2--5 filaments each. They have their origin in the ground-substance. As these filaments maintain their arrangement also in old cysts, they can be regarded as characteristic of Sarcocystis suicanis. The groundsubstance is homogenous; on the 32nd day p.i. it contained only metrocytes, and developed septa towards the interior of the cyst on the 47th day p.i. The parasites were reproduced by endodyogeny and appeared very similar to the structure of all cyst forming coccidians. Some old cysts degenerated fattily and the host cells were destroyed. The cysts of Sarcocystis suicanis with complete development of the protrusions of the primary wall can thus be differentiated from cysts of Sarcocystis suihominis with certainty.


[Detection of antibodies to Rickketsia prowazekii by using the antigen neutralization test].

The authors studied a possibility of using the antigen neutralization test with dry immunoglobulin typhus erythrocytic diagnostic agent for the purpose of detection of Rickettsia prowazeki antibodies. Blood sera of 315 healthy persons, 24 patients with sporadic typhus, and 18 laboratory animals immunized with R. sibirica and R. burneti, as well as with Proteus OX19 were examined. The results obtained pointed to the high specificity and sensitivity of the given serological test. A possibility of its use for antibody detection both in the typhus patients and in persons who sustained this infection in the past was demonstrated. In difference from the complement fixation test it permits to study anticomplementary sera.


[Model of meningococcal sepsis in mice].

The authors studied a possibility of obtaining experimental meningococcus sepsis model on mice. The use of cyclophosphane, iron compounds, yolk medium produced no significant organism. When 4--5% mucine was injected intraperitoneally together with meningococcus culture mice died with sepsis phenomena. Differences were revealed in the sensitivity of linear and mongrel mice to meningococcus infection--AKR mice proved to be more sensitive. At the same time it was found that mongrel mice weighing from 10 to 12 g could be used to induce meningococcus sepsis.


[Analysis of the dynamics of typho-paratyphoid infection morbidity over the years in the USSR].

Statistical materials of recording the number of patients and of the typhoid-paratyphoid infections morbidity level in Russia and the USSR from 1891 to 1976 was studied. A stable tendency to reduction of this morbidity was noted. In analysing the empirical and flattened--by 3 and 5 points--curves of the number of patients and the morbidity level a regularity of declining morbidity rises was revealed. Elevation periodicity persisted, despite the reduction of morbidity level. The mean duration of the whole cycle constituted 12 years. The period of increasing morbidity from minimal to maximal in each cycle constituted 4 years, and of the declination period--8 years. Formalized empirical series of the number of patients and of the morbidity level deviated from 1908 to 1956 not more than by 1 year from the formalized basic curve. Cyclic changes of typhoid-paratyphoid infections morbidity should be taken into consideration in determining the efficacy of prophylatic measures, particularly of mass vaccination.


[Parathyphoid B-antigen containing a complex of protective surface antigens].

The authors obtained a complex antigen from paratyphoid B bacilli containing complete O-, K- and H-antigens. The preparation was nontoxic and was characterised by marked antigenic properties. In intravenous and oral administration it stimulated production of specific O-, K-, and H-antibodies in high titres. Complex paratyphoid B antigen possessed a marked protective activity and provided intense immunity in subcutaneous and oral administration to experimental animals.


[Subclasses of human IgG. I. Production of antisera to IgG subclasses].

Guinea pigs were used for preparing antisera to human IgG subclasses for anti-IgG1, and rabbits--for anti-IgG2, anti-IgG3, and anti-IgG4. Schemes of laboratory animals immunization with myeloma paraproteins of four IgG subclasses were determined. Methods of antisera absorption for bringing them up to strict monospecificity were worked out. Antisera specificity were determined by the precipitation test after Ouchterlony with standard myeloma proteins in the concentration of 1 mg/ml, and in the passive hemagglutination test with erythrocytic antigenic diagnostic agents. Precipitating antisera to four human IgG subclasses were obtained.


[Ovarian morphology during experimental blastomogenesis in the cerebellum].

A morphological and histochemical study of the ovaries in 79 rats with cerebellar blastomogenesis due to DMBA in comparison with the ovaries of intact rats, rats with trauma of the cerebellum, rats with a paraffin pill implanted into the cerebellum, as well as with the ovaries of rats with a chemical cancerogenesis of the intestine, permitted to claim, that the most characteristic changes of the ovaries in cerebellar blastomogenesis consist in reduced amount of premordial follicules, athresia of the growing follicles and a formation of multiple follicular cysts. These processes are underlain by destruction of premordial follicles and a degeneration of the ovule in the growing follicles.


Induction of laccase in Basidiomycetes: the laccase-coding messenger.

Formation of the mRNA specific for the inducible forms of laccase was evidenced in Coriolus versicolor, Pleurotus ostreatus and Pholiota mutabilis. The half-life time of these mRNAs in the fungi species studied were, respectively, 30, 37 and 24 min. Molecular weight of the newly synthesized mRNA in Pleurotus ostreatus was about 4.5X10(5), consistently with the size of the inducible laccase protein. The polysome obtained from the ferulic acid-treated mycelium, synthesized in vitro a polypeptide with the electrophoretic mobility similar to that of laccase.


Binding of protoporphyrin and haemin to human spectrin.

Haemin and protoporphyrin IX, but not bilirubin, are extensively bound by human spectrin. The absorption spectrum of the bound haemin is indicative of coordination of the iron by nitrogenous ligands in the protein. The protoporphyrin IX generates difference spectra on binding, which change with ligand:protein ratio, showing the existence of at least two structurally distinct types of site. The binding of both ligands is complex, and may be cooperative. Binding isotherms, based on spectrophotometric titrations, are given. Haemin and protoporphyrin IX also bind strongly to erythrocyte ghosts. At ionic strengths near physiological we can find no evidence of binding of haemoglobin to spectrin, as judged by sedimentation velocity, and it appears that reported interactions of this nature represent only non-specific binding at low ionic strength.


Studies on red cell flexibility in spherocytosis using a polycarbonate membrane filtration method.

A method for studying red cell flexibility as reflected by red cell rigidity and fragility is described. Using an infusion pump, suspended red cells are filtered through a polycarbonate membrane with 3 micron pores. The filtration pressure, which is continuously monitored, is considered to reflect red cell rigidity. The hemoglobin released by the disruption of red cells passing through the membrane is regarded as an indirect measure of red cell fragility. In all of the patients with hereditary spherocytosis studied and in some of their symptomless relatives, the decreased flexibility observed was associable with increased rigidity of the red cell. In vitro effects of chlorpromazine and vinca alkaloid on red cell flexibility were also studied. High concentrations of chlorpromazine and vinblastine induced formation of spherocytes displaying altered cell flexibility.


Atypical nuclear structures in the buccal mucosal cells of the rhesus monkey.

During evaluation of cytologic buccal samples obtained from nine female rhesus monkeys over a period corresponding to three menstrual cycles, unusual nuclear changes were observed in the exfoliated cells. The changes ranged from small nuclear protrusions to bi-lobed and multi-lobed structures.


Folic acid binding protein in chronic granulocytic leukaemia: the effect of methotrexate.

Folic acid binding protein (FABP) has been measured in the supernatant of leukocytes of 12 patients affected with chronic granulocytic leukaemia (CGL). The folate binding capacity ranged from 1.37 to 697.52 pg/mg protein, showing a considerable heterogeneity. When the supernatant was preincubated with methotrexate (MTX), the inhibition of folic acid binding was complete in some cases whereas in others it was negligible: these findings have been confirmed by studying the 3H-MTX binding capacity by the same supernatants. In this case the range of bound 3H-HTX varied from 0.00 to 927 pg/mg protein. The presence of a binder in the cytoplasm of leukocytes might represent a new step in the regulation of endogenous folate metabolism. The MTX, widely used as an antifolate drug, may also be bound by FABP of CGL leukocytes, although in different amounts from case to case: this finding suggests a new point of interference of MTX in the folate metabolism. It has also been demonstrated that FABP, which is present in serum, may reduce the uptake of folate by leukocytes opening a new field of investigation on the megaloblastic transformation.


Blood group phenotypes and the origin of sickle cell hemoglobin in Sicilians.

As an approach to investigating the origin of sickle cell hemoglobin (hemoglobin S) in white persons of Sicilian ancestry, two groups of native Sicilians were tested for blood group evidence of African admixture. Among 100 unrelated Sicilians, the phenotypes cDe(Rho) and Fy(a-b-), and the antigens V(hrv) and Jsa, which are considered to be African genetic markers, were detected in 12 individuals. Among 64 individuals from 21 families with at least one known hemoglobin S carrier, African blood group markers were detected in 7 (11%). These findings indicate that hemoglobin S is only one of multiple African genes present in contemporary Sicilian populations. The occurrence of hemoglobin S in white persons of Sicilian ancestry is considered to be a manifestation of the continuing dissemination of the original African mutation.


Cytologic comparison of a human fibroblast culture chemically transformed in vitro with its non-neoplastic parent cell strain.

Paired cultures of glutaraldehyde-fixed, nontransformed and chemically-transformed human fibroblasts were examined by quantitative microscopy. Significant differences were found to exist between the two cell types with respect to projected cell and nuclear area, dry weight distribution, cell cytoplasmic thickness and intracellular distribution of protein. Quantitative measurements of nuclear DNA failed to reveal a major difference between the two cell populations.


Screening coagulation tests and clotting factors in homozygous beta-thalassemia.

In 30 children with homozygous beta-thalassemia the hemostasis screening tests (bleeding time, PT, PTT), platelet count and specific assays of clotting factors were carried out 25 days after their last transfusion. PT, PTT, and bleeding time showed minor variations; considerable thrombocytosis was found in splenectomized patients. Factors IX and XII were decreased in a high proportion of patients, the vitamin K-dependent factors (II, VII, IX, X) were slightly reduced and factors I, V and VIII remained within the normal range in a majority of patients. Hepatic failure resulting in defective protein synthesis does not explain the more marked impairment of factors XI and XII, which might be secondary to activation of the intrinsic coagulation and/or kallikrein systems following intravascular haemolysis and multiple blood transfusions.


Electrophoretic separation of alkaline and acid phosphatase isoenzymes from the pulp of monkey teeth.

Monkey pulps were homogenized in a Triton tris solution. After three centrifugation steps (800, 20000, and 105000 g) the supernatant was applied on acryl amide columns at pH 7.5 in a tris-diethyl barbituric acid buffer. Electrophoresis was performed at a constant current of 2.5 mA per gel column at 18--20 degrees C. Incubations for alkaline phosphatase (E.C. 3.1.3.1) were carried out at pH 8.3 using naphthol-AS-MX-phosphate as substrate and Fast Red Violet LB salt as coupler. Incubations for acid phosphatase (E.C. 3.1.3.2) were undertaken at pH 5.0 using alpha-naphtyl phosphate as substrate and hexazotized pararosanilin as coupling agent. After the incubations for alkaline phosphatase as well as acid phosphatase two bands showing enzyme activity were demonstrated. By means of treatment with heat (56 degrees C) prior to incubation or addition of vanadate or pyrophosphate to the incubation medium it was shown that the main part of the fast moving alkaline phosphatase band was sensitive to these procedures. The alkaline phosphatase of the slow moving band appeared to be resistant to heat or the addition of inhibitors.


Treatment of primary dysmenorrhea with prostaglandin synthetase inhibitors--a promising therapeutic alternative.

Three groups of patients with primary dysmenorrhea were treated with prostaglandin synthetase inhibitors. Thirty-one women received indomethacin at a dose of 25 mg x 3--4 per day usually starting one to two days before the onset of menstruation and 38 women received naproxen 250 mg x 3--4 per day usually starting on the first day of bleeding (open studies). Seventy-one per cent of the patients experienced moderate or good relief of pain following indomethacin and 67% following naproxen. In a third series a double-blind crossover study using the sodium salt of naproxen versus placebo in 26 patients showed that naproxen-sodium was significantly more effective than the placebo (p less than 0.05). At the doses employed, the prostaglandin synthetase inhibitors were not associated with any side effects of major concern. The study indicates that this form of therapy offers an effective alternative in patients who for some reason do not accept hormonal treatment.


Ultrastructural organization of the retinal pigment epithelium of the Cynomolgus monkey.

The ultrastructure of the retinal pigment epithelium of the Cynomolgus monkey is described. Particular interest is focused on the morphological basis for the functions of the pigment epithelium as part of the blood-retina barrier, as a metabolically active cell layer and as a participant in photoreceptor outer segment renewal.


Pressure effects on flow channels in the lining endothelium of Schlemm's canal. A quantitative study by transmission electron microscopy.

A quantitative investigation, using transmission electron microscopy, was conducted to determine the relative incidence of nuclei, giant vacuoles and their pores, non-vacuolar transcellular channels and minipores in the endothelium lining the trabecular aspect of Schlemm's canal at various levels of intraocular pressure in the range 0--50 mmHg. The eyes of twelve rhesus monkeys were used and prior to intracameral fixation, the intraocular pressure was maintained at the appropriate level for one hour. The results obtained from a single section analysis showed that the incidence of giant vacuoles, vacuolar and non-vacuolar transcellular channels and minipores could be related to pressure. An analysis of serial reconstructions of samples of the vacuoles indicated that vacuolar transcellular channels became more numerous and more enlarged as pressure was increased. We concluded that the transcellular pore system serves as a major outflow route for aqueous humour.


The role of zinc in total parenteral nutrition.

Zinc deficiency was observed in an infant receiving total parenteral nutrition (TPN) for chronic untractable diarrhoea. Clinical findings included low zinc plasma levels, skin lesions and loss of all the advantages of TPN such as weight gain, serum proteins and albumin increase and normalization of intestinal mucosa. Oral administration of zinc sulphate was the decisive factor making possible both the improvement of clinical and laboratory findings and alimentation by natural route.