Polyploidy and domestication: the origin and survival of polyploids in cytotype mixtures. The origin and survival of a polyploid in a mixture of this polyploid and its parent(s) is reviewed. With several examples a picture is drawn of the interference of cytotypes in a mixture of cytotypes. Some natural polyploids, both wild and domesticated, are very successful. They, like bread wheat and banana, largely replaced their parents. The same is true for some artificial polyploids like autotriploid hybride sugar beet in Europe and autotetraploid perennial ryegrass. But when grown together with their parents for several generations they will disappear from this misture. Although in South America under primitive conditions, diploid, triploid, and tetraploid potatoes are grown, elsewhere only the tetraploids have survived. Various causes are presented to explain why the diploids and triploids succumbed. Autotetraploids of maize, rye, barley, and rice cannot maintain themselves in diploid/tetraploid mixtures. The maintenance of diploid or tetraploid rye varieties is less difficult as both are "self-cleaning" with respect to the other. Only two haploid cultivars exist but they can only maintain themselves with the help of man. It is concluded that the survival chances of a polyploid after its origination is low. Firstly, under conditions of random sampling a rare type has a very small chance of occurring in the next generation. Furthermore, seedset of triploids and tetraploids is often low which limits their survival. In addition, in mixtures of cross-fertilizing diploid and autotetraploids the n gamete has an advantage over the 2n gamete. This limits the survival of the autotetraploids again. It is concluded that our knowledge of the the mutual interference of cytotypes in a cytotype mixture is quite limited. Much more research is needed and some proposals concerning this research are made.


Uses of wheat aneuploids.

Uses of wheat aneuploids. There is available in wheat a unique series of aneuploids ranging from all 21 possible monosomics to complex types that are simultaneously deficient for one chromosome and duplicate for another. Furthermore, lines with chromosomes from related alien species either added to or substituted for wheat chromosomes are in common cytological use. This contribution condiders the use of this range of material in studies designed to elucidate the evolutionary relationships of the species, in investigations of the genetics of a polyploid with cytological diploidization, and in potential breeding manipulations.


Physiology of polyploids.

Physiology of polyploids. Polyploidy, a multiplication of the whole chromosomal complement, is a very widespread phenomenon in higher plants. Natural polyploids have been suggested to be more successful than their diploid progenitors under certain conditions. This success may be due to "balance hybridity," i.e., the combination of the advantage of hybridity together with the balancing of excessive segregation and sterility by chromosome doubling, and possibly also to the effect of genome multiplication per se. The latter effect can be studied independently of the effect of other genetic changes only in autopolyploid newly derived from single ancestral strains. The existing knowledge on the effect of genome multiplication on the physiology of the plant is fragmentary and based on too narrow a representation of plant types; much of the information available on the effect of genome multiplication pertains to the tomato. Various aspects of polyploidy are discussed according to levels of function and organization: gene action, cell characteristics, growth substance, water balance, ion balance, stability of phenotypic expression and the response of polyploid plants to stress. Future work on the physiology of autopolyploid plants should be directed towards: (1) the investigation of more representative experimental systems that should include genetically homogeneous and heterogeneous species of both wild and cultivated plants; and (2) diploid-polyploid comparisons on the level of isolated tissues and cells, in addition to the whole plant.


Studies on urea hydrolysis. Part 2. Effects of some heavy metals on urease activity. The effect of some heavy metals on the urease activity was studied in a pure system using jack bean urease (JBU). While Mn showed no effect, copper reduced the enzyme activity more than did Zn or Fe at high concentrations (100 ppm). At a low concentration, iron reduced the enzyme activity more than at a high concentration. Inhibition of the urease activity was induced by less than 0.1 ppm Fe, 0.5 ppm Cu, and 10.0 ppm Zn. In the soil, these heavy metals inhibited the JBU in this order: Fe++ greater than Cu++ greater than Zn++. The possibility is discussed of using heavy metals to delay urea hydrolysis in soils.


Incidence of Fusarium moniliforme Sheld. in Zea mays L. in the rainforest zone of Nigeria. 45 seed samples from 7 states of the rainforest zone of Nigeria (Ogun, Ondo, Oyo, Bendel, Anambra, Imo, and Cross River) were screened for phytopathogen incidence. Whereas Drechslera maydis was found in 30 and Cephalosporium maydis in 79% of the samples were infected by Fusarium moniliforme, with 70% of the samples showing heavy infection. In view of the widespread nature of this economically important fungus on maize in the main cultivation area of Nigeria, the necessity for routine laboratory seed health tests is clearly indicated.


Measurement of lung volumes from supine portable chest radiographs. Lung volumes in supine nonambulatory patients are physiological parameters often difficult to measure with current techniques (plethysmograph, gas dilution). Existing radiographic methods for measuring lung volumes require standard upright chest radiographs. Accordingly, in 31 normal supine adults, we determined helium-dilution functional residual and total lung capacities and measured planimetric lung field areas (LFA) from corresponding portable anteroposterior and lateral radiographs. Low radiation dose methods, which delivered less than 10% of that from standard portable X-ray technique, were utilized. Correlation between lung volume and radiographic LFA was highly significant (r = 0.96, SEE = 10.6%). Multiple-step regressions using height and chest diameter correction factors reduced variance, but weight and radiographic magnification factors did not. In 17 additional subjects studied for validation, the regression equations accurately predicted radiographic lung volume. Thus, this technique can provide accurate and rapid measurement of lung volume in studies involving supine patients.


Haemodynamic effect of the venom of Bitis Gabonica in the dog. Intravenous injection of 0.125 mg/kg of venom of Bitis Gabonica in the anaesthetized dog produces an immediate but reversible decrease in total peripheral and coronary vascular resistance. Stroke volume show a transient increase followed by an irreversible reduction. A second dose of 0.25 mg/kg produces the same effect on total peripheral and coronary vascular resistance, but furtherly reduces the stroke volume. A third dose of 0.50 mg/kg kills the animal after an extreme reduction of the stroke volume. The progressive decrease of the stroke volume might be due to a failure of the ventricle to relax, whereas its transient increase immediately after the injection depends on the abrupt fall of the total peripheral resistance.


Tryptophan metabolism in animals with dermatitis. I) In Rats. Tryptophan metabolism "via kynurenine" after load of amino-acid has been studied in urine of rats before and after induction of experimental light-conditioned dermatitis with psoralen. Tryptophan load in animals during the acute phase of dermatitis (one day after induction) causes a markedly increased urinary excretion of total metabolites in comparison with that obtained before dermatitis. After six days of dermatitis, when the skin damage was in repair, the excretory values after tryptophan load in rats are only slightly increased indicating that the metabolic disturbance is correlated with the skin damage.


Tryptophan metabolism in animals with dermatitis. II) In guinea pigs. Tryptophan load in guinea pigs after induction of a photodermatitis from psoralen caused marked increase of urinary excretion of total metabolites "via kynurenine" in comparison with that obtained before dermatitis. Xanthurenic acid is the metabolite which showed the most increased levels in urine during dermatitis. This dermatitis from furocoumarin caused an alteration of tryptophan metabolism in guinea pigs as well as rats, but species differences in the excretion of metabolites after amino acid load are observed.


[Evaluation of intestinal absorption of calcium by means of double-isotope methods and oral administration of the tracer]. The percent intestinal absorption of calcium was measured in normal volunteers and in patients with idiopathic hypercalciuria employing the deconvolution method, the ratio of the two administered isotopes at equilibrium and the percent of dose present in plasma 2 hr after oral administration of the tracer. Comparison of results obtained showed that the technique based on the ratio between the two radioisotopes overestimates intestinal absorption by about 9% with respect to values calculated with the deconvolution method, but gives results comparable to those determined by oral administration of the isotope. The percent dose of the tracer 2 h after i.v. administration is closely correlated with the size of the miscible calcium pool. A less significant correlation exists between the size of the pool and percent of the dose 2 h after oral administration.


[Effects of surgery and anesthesia on serum immunoglobulins]. Serum immunoglobulins levels after surgery with and without anaesthesia are reported. No significant change was found after surgery without anaesthesia; significant changes of serum Ig (A,G,M) were observed in surgery with anaesthesia (60-180 m') group on day 1 following operation. This Ig decrease is probably due to a reduced immunologic response by long anaesthesia.


[Visco-elastic characteristics of the rat aorta]. In order to estimate wave propagation "in vitro", aortic compliance has been studied by means of rings and stripes from 6 adult male Wistar rats. Lengthening and shortening maneuvres have been performed; the pulse transmission rate was evaluated by calculating the elastic modulus during the maneuvres. A Norepinephrine infusion has been done. Results obtained show that transmission rate is higher in shortening than in lengthening phases. Norepinephrine did not significantly affect the values. The rate values were not greatly different whether "in vitro" or "in vivo". By increasing specimen stress, the rate too was increased, but the amount was lower than "in vivo" values. Hence it was assumable that rate variations "in vivo", should be partially influenced by elastic modulus, and a vegetative intervention should be implied.


[Measurement of the velocity of the pulse wave]. Pulse wave transmission rate has been measured "in vivo" in 6 male anaesthetized Wistar rats, by means of cannulae, inserted both in carotid and femoral arteries. The measure has been done by calculating the time delay of several corresponding levels in the two pressure pulses: at the foot, during the ascending phase, at the peak. Three different intervention have been carried out: Ach, NA, blood transfusion. The transmission rate outcame higher at the pulse foot than at the peak, in control animals and in Ach and blood transfusion interventions. The NA intervention inverted this behaviour, where the increase in transmission rate did not correspond to the rate of pressure growing. The possible influences of a vegetative component on arterial viscoelastic behaviour are discussed.


[Effects of dopamine, noradrenaline and isoproterenol on pulmonary circulation in anesthetized dogs]. Experiments were performed on 19 anaesthetized open-chest dog instrumented with polyethylene catheters inserted: into the aorta, in pulmonary artery and in left atrium and with an electromagnetic flow-transducer placed around the ascending aorta in order to record : systemic arterial and pulmonary pressures, mean left auricular pressure and phasic aortic flow. Heart rate, stroke volume, total systemic and pulmonary resistance, cardiac work were moreover calculated. Each dog was given intravenously by slow infusione : Dopamine (micrograms 5--10--20/kg/min/ 5 min), Isoproterenol (microgram 0.125--0.25--0.5/kg/min/5 min) and Norepinephrine (microgram 0.25--0.5--1 /kg/min/5 min). Results obtained on systemic hemodynamics agree with those reported by many other investigators. On pulmonary circulation : Isoproterenol, at the tested doses, elicited vasodilator effects, Norepinephrine increased total pulmonary resistance but not pulmonary vascular resistance, while Dopamine did not modify or slightly reduced vascular pulmonary tone.


[Influence of serotonin on some serum enzyme activities in rats]. The serotonin injected intraperitoneally in rats (20 mg/Kg of body weight) modifies some seric enzymatic activities (LDH, alpha-HBDH and CPK) at different times from the injection (30, 60, 90 min.), acting probably on membrane permeability and on intracellular metabolism.


[Oxygen consumption in organs of rats treated with serotonin]. The serotonin injected intraperitoneally in rats (20 mg/Kg of body weight) increases the oxygen utilization of slices of heart, liver and muscle with a maximum value after 60 min from the injection. The serotonin, probably, acts on intracellular metabolism increasing some enzymatic activities or metabolic pathways.


Molecular mechanism of general anesthesia: I. Fluorescence studies in mitochondrial membranes. We have tested the working hypothesis that anesthetics, by labilizing lipid-protein interactions, induce conformational changes in membrane proteins involved in the transmission of neural impulses. In the first communication of this series we report that general anesthetics induce changes in the fluorescence of the probes ANS and NPN in model membranes, lipid vesicles and mitochondria. The changes observed concern the quantumyield but not the position of the emission maximum. Such changes may be interpreted as due to fluidization of the membrane core (NPN), accompanied by variable effects in the membrane surface(ANS).


Molecular mechanism of general anesthesia: III. Kinetic studies on erythrocyte ghost acetylcholinesterase. General anesthetics inhibit erythrocyte membrane-bound acetylcholinesterase. Release of the membrane-bound enzyme by sonication into a soluble form induces a loss of sensitivity to anesthetics. Reconstitution of the solubilized enzyme with phospholipids restores its inhibition by anesthetics. The results suggest that anesthetic inhibition of acetylcholinesterase is mediated through the lipid bilayer.


An improvement of the analytical description of temporal variations of plasma and total platelet activities, studied using 75Se-methionin as an in vivo tracer. In this work we have re-examined our previous model for the analytical description of temporal variations of plasma and total platelet activities, introducing a mathematical simplification by means of elimination of a cumbersome and deforming parameter. We give here 1) interpolation formula 2) complete list of instructions of our program for computer data processing.


[In-vitro antimicrobial activity of 2 aminoglycoside antibiotics: tobramycin and gentamycin]. It has been determined the in vitro antibacterial activity of two antibiotics on 409 bacterial stocks isolated from several pathologic materials and composed by E.coli,Propeus,Salmonellae,Pseudomonas,Staphylococcus aureus. The Tobramicin has shown to have activity against all stocks of E.coli(82),Pseudomonas aeruginosa (62) and Salmonellae (21) and to have a better activity in comparison with Gentamicin also against Proteus and Staphylococcus aureus.


[Changes in osmotic resistance of erythrocytes of human blood caused by Vipera berus venom]. The effect of Berus viper's venom on the osmotic globular resistance of human blood, incubated for a period of 2 hours at 20 degrees C with amounts of venom in the range of 200 to 400 gamma/ml of blood, has been studied. The hemolytic effect occurs to a greater extent at NaCl concentrations higher than 0,60%.


[Vitamin C in the plasma and leukocytes of Italians in different periods of the year]. After briefly mentioning the factors which influence the vitamin C levels in tissues, the findings are reported of an investigation, conducted on 11 volunteers, in which some variations were revealed in vitamin C concentrations in the plasma and in the leukocytes of the subjects examined during a period of one year. The lowest levels were found in the months of March and December.


[Therapeutic action of vitamin C on cholesterol metabolism]. As a part of the research work on the role played by Vitamin C on lipidic metabolism, the effects on man were considered that result from the administration of high vitamin C doses, chiefly with reference to the serum levels of colesterol, of total lipids and of triglycerides. Our research was conducted on male subjects of 65-90 years, who were administered 3 g/day of vitamin C for three weeks. Our findings show that the administration of high vitamin C doses causes a statistically significant decrease in colesterol, in total lipids and in triglycerides, in all the subjects under consideration. This takes place not only when colesterol, total lipids and triglycerides present normal serum levels, but also when such levels show an increase. Conversely, vitamin C significantly increases, with treatment, in all subjects treated, both in plasma and in leukocytes.


Influence of phospholipids on the respiratory activity of embryonal heart cells cultured in vitro in presence of different ethanol concentrations. The influence of phospholipids on respiratory activity of embryonal heart cells, trated with certainly harmful concentrations of ethanol, has been discussed. It has been concluded that when the cell is deeply impaired the administration of phospholipids does not seem to have positive effects. In this condition an irreversible morphological alteration has been induced.


[Histochemical demonstration of tetrahydrofolate dehydrogenase in human bone marrow: apparent enzymatic induction after administration of folic acid antagonists]. Folate antagonists interfere to a varying extent with the histochemical demonstration of tetrahydrofolate dehydrogenase. Some aspects of this interaction are investigated in normal hemopoietic cells of patients following antitumor treatment with methotrexate. In this situation the histochemically detectable activity of tetrahydrofolate dehydrogenase exceeds the control levels (apparent enzymatic induction). A protection of the enzyme-metabolite complex from degradation and diffusion might be effective for the changes in reaction intensity.


[Studies of the half-life of plasma parathyroid hormone: rate of disappearance of immunoreactive fragments of the hormone after surgical removal of the parathyroid adenoma in primary hyperparathyroidism]. The disappearance rate of immunoreactive plasma parathyroid hormone (iPTH) was studied, employing two different antisera, following removal of parathyroid adenoma in patients with primary hyperparathyroidism. One antisera contained antibodies against both the NH2 region and the COOH terminal of the molecule (antiserum 211/32, Wellcome Laboratories), the other contained antibodies against antigenic sites of the terminal COOH portion (Immuno Nuclear Corporation antiserum). The iPTH plasma level dropped in all patients following removal of the adenoma. The half-life was longer than that of the native hormone and shorter than that of the terminal fragment with both antisera, being 38.8 min for the 211/32 and 32.9 min for the I.N.C. antiserum. Whilst this finding might be expected for the 211/32 antiserum, on account of its characteristics, it is difficult to offer an explanation for the observed half-life of the I.N.C. anti serum which is specific for the terminal COOH region. These results appear to suggest that the terminal COOH fragment may be further metabolized and that its longer half-life, observed by other authors, is due to the antisera used recognizing the antigenic sites in a fragment smaller than the terminal COOH portion of the molecule, rather than to the effective half-life of the entire fragment.


[Values and limitations of the radioimmunological determination of plasma parathyroid hormone in the study of the functional activity of the parathyroid glands]. Aim of the present study was to establish the limits and difficulties prevailing in RIA of PTH due to different specificity of antisera. Studies were carried out on normal volunteers and 36 patients with primary hyperparathyroidism (HPT) employing two different assay techniques a) 211/32 antiserum from Wellcome Lab. and b) Immuno Nuclear Corporation Kit. Plasma iPTH values were higher in most primary HPT patients than in normal subjects with both techniques. It is possible nevertheless to differentiate the primary HPT patients with normal plasma iPTH values from normal subjects by correlating plasma iPTH values with corresponding serum calcium values.


[Long-term treatment with lithium salts and cerebral electric activity. Experimental research]. An eeg study was carried out in rabbits to investigate the neurophysiological effects of chronic lithium clorure treatment. The Monnier and Gangloff's stereotaxic method was used for recording cortical and deep structure activity. Lithium clorure was administered i.p. at doses of 20 mg/Kg/die for 15-22 days (mean plasmatic levels: 0.04 mEq/l). The eeg changes consisted in synchronization of the cortical activity, slowing of the deep structure activity and increase of CAD spiking. The most interesting finding was the appearance of peculiar periodic spikes in the CAD and subcortical structures. A similar pattern has been previously described by us in rabbits treated with repeated ECT.


[Effects of lidocaine, mepivacaine and prilocaine on the detrusor muscle of the rat urinary bladder]. Lidocaine, mepivacaine and prilocaine cause in rats an increase of the frequency of the spontaneous contractions and an increase of the tone on the detrusor muscle of the urinary bladder. These effects are not antagonized by atropine and by fentola mine. On the contrary verapamil and papaverine antagonize these above effects.


[Correlations between the processes of cell differentiation and development of blood vessels in the (chick embryo) adenohypohhysis]. Utilizing semi-thin and, respectively, thick sections after indian ink injections, we have analyzed morphohistogenesis and vessel development in the adenohypophysis of chick embryos from the 4th to the 19th incubation day. Our preliminary results indicate that a close correlation exists between cellular differentiation and vasculogenesis. Vessels begin to enter the gland only at the 6th day when the first endocellular granules become detectable, and, from the 10th day, they markedly increase in number and size, gradually acquiring a peculiar sinusoidal arrangement around cellular groups, as cell differentiation further progresses.


[Study of the wave-form of the stapedial reflex in response to sonorous stimuli of different intensity]. The threshold of the acoustic reflex and its pattern in response to different intersity stimuli, was investigated by means of the signal-averaging technique in 10 normal ears. Trains of tone bursts between 100 and 0 dB HL were used. The frequencies tested were 500, 1000, 2000 and 4000 Hz. In all subjects the pattern of the acoustic reflex for stimuli between 110 and 100 dB HL was biphasic, with an initial positive plateau followed by a longer negative one. For stimuli < 80 dB HL the pattern of the reflex was monophasic, characterized by a single positive peak (latency between 120 and 170 msec).


[Alpha-thalassemia in Puglia. II. Neonatal screening for Bart's hemoglobin]. 550 blood specimens from the umbilical cord of newborn babies from Apulia have been screened in order to detect Hb Bart's. The electrophoresis of the haemoglobin by Cellogel (Tris Glycine pH 8.6) carried out on the 550 specimens have revealed in 43 variable quantities of Hb Bart's: 34 cases (6,18%) showed non measurable quota, whereas in the other 9 cases (1,63%) Hb Bart's varied from 2,19% to 26%. The haemoglobin biosynthesis "in vitro" of the baby presenting 26% of Hb Bart's has been reported.


[Study in vitro of the biosynthesis of Hb in alpha-thalassemic subjects of Puglia]. An haematological study and haemoglobin biosynthesis in vitro carried out on the members of family from Ostuni (Apulia), three of which present Hb H in quantities varying from 26 to 28 and 29%, has been reported. On the basis of the haematological and biosynthetical data, the Authors think that the genetics of the alpha-thalassemia in the family under observation is similar to that observed in South East Asia according to the hypothesis of the existence of two alpha loci. The biosynthetical data fall into the values obtained by Kan and Coll. even if with slight differences.


Organization of the visceral afferent representation in the cerebral cortex. In experiments on cats which had been narcotized with chloralose and immobilized with myo-relaxants, we have studied cerebral cortical responses to stimulation of the visceral system. A peculiarity of the visceral afferent representation is the fact that the convergence of visceral and dermomuscular impulses is achieved with predominance of somatic signals in the cortical zones of visceral representation, with the exception of the focus of maximal activity (FMA). A second peculiarity is the fact that the visceral afferent systems develop habituation to prolonged stimulation. The principles of this development are similar to the general principles described in the literature for other sensory systems.


Possible mechanism of the selectivity of the cytostatic action of antineoplastic preparations. A model of the phenomenon of selectivity of antineoplastic phase-specific preparations in leukemia, based on the assumption that any proliferating cells are equally sensitive to the action of such preparations, is suggested. Therefore, selectivity, the concept and fundamental significance of which were formulated and substantiated by the authors earlier, can be expressed in terms of the proliferative pathways of the normal and leukemic populations, the ratio between which thus plays the deciding role in the selection of the optimum system of therapy. The concept of maximum selectivity, which is a convenient numerical characteristic of a preparation, was introduced. A comparative quantitative analysis was made of a number of antineoplastic preparations (vinblastine, vincristine, amethopterin, arabinosylcytosine, azaserine); it showed that the conclusions of the model do not contradict the experimental data.


Absorptive function of peripheral blood neutrophils in irradiated animals. It was shown in experiments on rats, dogs, and monkeys, irradiated with x rays or the gamma rays of 60 Co, that a decrease in the indices of phagocytosis is observed only 3-4 weeks after irradiation. It is concluded that the absorptive function of mature neutrophils in radioresistant, and the cells whose maturation occurred after the influence of ionizing radiation are inadequate.


Influence of ultralow temperatures on the translating activity of cell-free extracts of different origins. The influence of various systems of freezing (-196 degrees C) and thawing on the protein-synthesizing activity of cell-free extracts from Krebs II ascites carcinoma of the rat liver and from wheat germ was studied. It was established that the biosynthesis of proteins, stimulated by exogenous templates, is decreased in the case of slow systems of freezing and warming of cell-free extracts from Krebs II ascites carcinoma. Similar results were obtained in an investigation of the endogenous protein-synthesizing activity of a cell-free extract from the rat liver and Krebs II ascites carcinoma. No significant decrease in the translating activity of the cell-free extract from wheat germ was observed in the investigated systems of freezing and warming. It was shown that the greatest sensitivity to the action of low temperatures is possessed by a cell-free extract from Krebs II ascites carcinoma.


The possibility of passive transport of histamine through biological membranes. The possibility of transport of free and heparin-bound histamine along the concentration gradient through bimolecular lipid membranes (BLM) and the influence of various factors on it was studied. It was shown that histamine is capable of diffusing through BLM in the form of a singly charged cation. In contrast to histamine, neither heparin nor the histamine-heparin complex (HsHC) penetrates through BLM. It was established that the action of histamine-liberating factors -- increasing the ionic strength to 0.15 and the addition of trypsin to the solution -- on HsHC leads to the appearance of transport of histamine through the BLM as a result of an increase in the concentration of free histamine in solution.


The hypothalamo-hypophyseal system in female rats with an anovulatory cycle. An electron-microscopic study was made of the suprachiasmatic and acurate nuclei of the hypothalamus, the intermediate and anterior lobes of the hypophysis in infertile female rats, sterilized by one injection of testosterone propionate in the critical period of their sexual development. Deformed synapses were detected on the bodies of the neurocytes of the suprachiasmatic nucleus, the accumulation of secretory granules and synaptoid vesicles in the nerve terminals of the intermediate lobe, and an intensive formation of secretion by the prolactin-producing adenocytes of the hypophysis. The mechanism of the masculinizing effect of androgens at the level of the hypothalamus and the possibility of correction of the anovulatory cycle in sterile females are discussed.


Study of the influence of certain antitumor preparations on the population of hematopoietic stem cells. The influence of antitumor preparations 1,2-bisdiazoacetylethane (diazan) and N-nitroso-N-methylurea (NMU) on the inhibition of colony formation after sublethal irradiation and on migration after nonuniform irradiation of mice was investigated by methods of endogenous cloning of hematopoietic stem cells. It was shown that both preparations in the therapeutic doses used in experimental oncology (diazan 150 mg/kg, NMU 8 mg/kg) have no mitostatic effect on the hematopoietic stem cells, while NMU also does not influence their migration. Diazan somewhat stimulated the migration process.


Topical timolol in open-angle glaucoma.

Topical timolol in open-angle glaucoma. Timolol theraphy was started in 37 patients with open-angle glaucoma whose intraocular pressure was inadequately controlled with maximum medical theraphy or who were having side effects with conventional medication. The intraocular pressure was substantially reduced by timolol in most of the patients, and there were relatively few side effect. A slight decrease in the pulse rate occured in some patients. The pressure-lowering effect was additive to that of other medications the patients were receiving, and was particularly useful in 13 of the 16 patients whose intraocular pressure had previously been inadequately controlled by maximum medical theraphy. The pressure-lowering effect appeared to be well sustained in most patients, although the pressure rose slightly in some.


Amblyopia and the monofixation syndrome. Children with a Monofixation syndrome often show a small angle constant esotropia with an overlying esophoria of variable and often large angle. Commonly the phoria is well controlled unless the child is very tired, or the eyes are dissociated. Treatment of a concomitant amblyopia by patching may result in an inability to control the phoria, with breakdown of the strabismic angle to a large esotropia. Illustrative cases are presented.


Prismotherapy in intermittent exotropia. A preliminary report. Twenty-five patients with intermittent exotropia and suppression were prescribed prisms which neutralised their maximum deviation. Thirteen patients failed to wear their prisms properly and served as controls and none were cured. Eight of the 12 patients who wore their corrective prisms more than half the time they were awake were cured.


Vitreous and retinal surgery in pseudophakia. We review scleral buckling and vitrectomy procedures in thirteen pseudophakic eyes. Pre-operative difficulties in visualizing the fundi were few. Despite operative complications due to the implant, 90% of the retinas were reattached. Late complications involving particularly the anterior segment in both the buckling and vitrectomy groups caused the poor visual results.


Retinal detachment and pseudophakia.

Retinal detachment and pseudophakia. Retinal detachments occur in up to 3.6% of pseudophakic patients. The intraocular lens makes it hard to see the peripheral fundus but the small pupil ophthalmoscope is a valuable help. The functional and anatomic success rates after operation are about 5% less than those of patients with aphakic retinal detachments matched for age and sex. I present fifteen cases of pseudophakic detachment. Any manipulation likely to induce contact between lens and cornea such as collapse of the globe after drainage of fluid or gas injections should be avoided. Careful examination of the fundus before and after cataract extraction and careful selection of paients for lens implantation are the only means of reducing the incidence of retinal detachment.


Seidel's test using 10% fluorescein.

Seidel's test using 10% fluorescein. A 10% solution of fluorescein applied topically shows a leak from the anterior chamber better than a 2% solution. Fluorescein changes color because it is diluted by the leaking aqueous and not because its pH is changed.


Evaluation of the Schirmer tear test.

Evaluation of the Schirmer tear test. We used the Schirmer filter paper test to measure tear production in 10 healthy women after instillation of local anesthetic drops at the same time of day for 30 or 31 consecutive days. We found that it was not a reliable indicator of tear production. The results varied widely even on the same subjects many of whom would, according to the standards for interpretation of the test, have been judged to produce an inadequate amount of tears.


Eye enlargement in birds induced by dim light. We here report changes in eye weight and other measurements, in chickens reared in dim light. These effects are distinguished from those seen in light-induced avian glaucoma (brought on by exposure to continuous light). We confirm and extend the results of Berkovitz and Harrison on the dim light effect, but we differ from Axmith and Morin, who were apparently unable to reproduce light-induced avian glaucoma. We cannot yet offer an explanation as to the mechanism(s) of eye damage in either light-induced avian glaucoma or dim light-induced macrophthalmos.


Biochemical analysis of the cornea stored in steroid medium. We wished to measure changes in the tissue mass and the deoxyribonucleic acid and protein content of guinea pig corneas stored for up to 21 days in tissue culture medium with or without 1 microM hydrocortisone. Full-thickness discs 4 mm in diameter were cut from the corneas for measurement of the three variables. Whether the disc came from a steroid-treated cornea or not, and whether it came from a fresh cornea, hydrocortisone did not appear to have any adverse effect on the features studied.


Bilateral choroidal osteoma after nine years. We describe bilateral choroidal osteoma in a young woman. Photographs showed enlargement of both tumors as we followed the progress of her disease for nine years before making the diagnosis.


Massive retinal gliosis simulating choroidal melanoma. A pigmented fundus lesion in a 47-year-old woman gave a positive 32P test result and angiography showed a separate tumor circulation suggesting a diagnosis of choroidal melanoma. Examination after local resection of the tumor revealed massive retinal gliosis, a rare condition not normally considered in the differential diagnosis of choroidal melanoma. We review the clincial and histologic features that differentiate massive retinal gliosis from choroidal melanoma and astrocytic hamartoma.


Failed dacryocystorhinostomy in Paget's disease. We describe a patient with bony closure of a DCR due to monostotic Paget's disease. The condition may exist without biochemical, radiological or radioisotope changes. The abnormal bone must be removed and a Jones glass tube placed in the rhinostomy.


Ultrasonography and computerized tomography in the diagnosis of unsuspected uveal melanoma with proptosis. A man of 62 developed sudden proptosis of his blind right eye after a blow to the head. A posttraumatic carotico-cavernous fistula was diagnosed, but B-scan ultrasonography and computerized tomography showed a large choroidal malignant melanoma wit retrobulbar extension.


The analysis of anisocoria. The use of photography in the clinical evaluation of unequal pupils. Unequal pupils are common and can be difficult to sort out. A flow chart is presented to help in localizing the cause for anisocoria. Also, an inexpensive and simple camera is suggested for use in accurately measuring pupils.


Aspects of cuprogenic disorder in Wilson's Disease in India. A brief account is given of some aspects of Wilson's disease in India, studied during the periods 1959 to 1967 and 1970 to 1978, with emphasis on disordered parameters of copper metabolism. Among the latter, serum copper oxidase (representing caeruloplasmin) was found to be the most constant laboratory evidence of Wilson's disease. It wad drastically lowered in all patients in both periods (25 and 44 patients respectively), when compared to its level in the parents and siblings of the patients, in other neurological patients and in normal subjects serving as controls. The other constantly involved parameter was direct-reacting serum copper which was highly significantly elevated in the patients compared to the other groups. Most of the patients presented with a predominantly neurological form of the disease, smaller groups presenting with predominantly osseomuscular or hepatic forms. The mean age of patients in both periods was approximately 13 years.


The neurological aspects of atrial myxoma. 2 cases of left atrial myxoma are presented, with a review of the recent literature on the topic, in order to bring this rare condition to the attention of clinicians. Both cases presented to the Neurological Unit of the Queen Elizabeth Hospital during 1978. The cases helped to emphasise the role of echocardiography in the routine appraisal of the stroke patient, especially if there are multiple lesions or if the patient concerned is young. The second case raised interseting questions regarding electrocardiographic changes associated with altered states of consiousness. Until recently cardiac myxomas were usually a postmortem diagnosis, but now with the effective combination of echocardiography and cine-angiography, cases are being effectively diagnosed and treated. It is hoped that with an increased awareness of the condition, diagnosis will be made sooner and thus prevent more severe sequelae occuring.


Primary lymphoma of the central nervous system: a case report. A 46-year-old female presented with a 1-week history of mental change, confusion and headaches. Investigations revealed evidence of sterile meningitis. CAT scanning of the brain demonstrated marked contrast enhancement around the ependyma, and later examinations showed extension of the process deep into the white matter, Cerebral biopsies were non-diagnostic and, despite ventricular drainage and treatment with antibiotics and high dose steriods, the patent died. At postmortem there was extensive tumour tissue distributed in a butterfly shape around the ventricles, and microscopy revealed typical apperances of primary CNS lymphoma. On the basis of the experience of this case and a review of recent literature, it is suggested that the CAT scan appearances of this tumour are quite typical, and that cranial irradiation may be justified in the absence of specific histological diagnosis.


Idiopathic communicating hydrocephalus: the prognostic significane of ventricular size after shunting. A description is given of the dramatic, sustained recovery of 3 demented and neurologically disable patients with idiopathic communicating hydrocephalus after they underwent ventriculo-atrial shunting. In those patients there was no significant change in ventricular size after the ventriculo-atrial shunting. 1 of the patients also had cortical atrophy. Hypertensive vasculopathy and multiple infarcts may be the explanation in 2 of the patients. Reveiw of the literature results in the following conclusions: 1) the CAT scan alone, perhaps combined with intrathecal "Amipaque' cisternography, provides the maximum information with the last trauma and may assist in the selection of patients for shunting. 2) Test removal of 20 to 30ml of CSF may be as satisfactory as pressure monitoring and infusion techniques in the prediction of successful shunting. The following do not have a reliable predictive value: a) The presence of cortical atrophy (shunting may sometimes be effective in mild to moderate cortical atrophy) b) The period of onset of symptoms c) The ventricular size before shunting and its alteration after shunting.


Factors likely to affect the development of multiple sclerosis in patients presenting with optic neuritis in a tropical and subtropical area. The relationship between optic neuritis (ON) and multiple sclerosis (MS) in a subtropical climate is examined. 105 cases of ON were followed for varying periods over 26 years. The factors studied included place of birth, sex, age at onset, presence of recurrent ON, the interval to the onset of MS, and HLA antigen typing. 55% of cases developed evidence of definite MS. The majority of cases who went on to develop MS had their onset of ON between 21 and 40 years of age. The subtropical climate did not cause any significant variation in incidence. However those case who had HLA Bw4 appear to be protected from developing MS.


Antiopyrine half-life as a measure of hepatic enzyme induction: clinical applications in a chronic epileptic population. Quantitation of hepatic microsomal enzyme induction in epilepsy has a theoretical role in identifying patients at risk of metabolic bone disease, in assessing drug compliance and in predicting anticonvulsant dose/serum level relationships. The clinical usefulness of antipyrine half-life as a measure of enzyme induction in chronic epilepsy has been explored in this study. Mean antipyrine half-life in a control group (mean 10.7 hours SD 2.0) was significantly longer than in an epileptic group (mean 5.6 hours SD 2.3). Antipyrine t1/2 did not distinguish epileptics with osteomalacia from other epileptic patients and half-lives were similar in patients treated with phenytoin and a barbiturate to those in patients on phenytoin alone. No significant correlation was found between antipyrine half-life and phenytoin dose or between half-life and phenytoin level. In 5 patients with low serum levels of anticonvulsant, antipyrine kinetics suggested poor compliance in 3 and rapid hepatic phenytoin degradation in 2. This study suggests that measurement of antipyrine half-life may be useful in assessing drug compliance, but is not useful in predicting the onset of osteomalacia or dose/serum level relationships.


Urticaria pigmentosa---change in conscious state associated with rise in plasma histamine levels. The case is described of a 42-year-old man with urticaria pigmentosa and documented systemic mastocytosis who had 2 episodes of loss of consciousness, headache, nasal stuffiness and faecal incontinence, following a swim in a river. Under controlled conditions the patient was subjected to immersion of the right hand to icewater for a period of 2 minutes, followed by 2 minutes of strenuous exercise. Similar symptoms involving change in conscious state were evoked with accompanying rises in plasma histamine levels. These findings suggest that histamine is at least one of the major mediators of the change in conscious state that is reported rarely in these patients and draws attention to the neurological facets of this rate disorder.


Ischaemic optic neuropathy.

Ischaemic optic neuropathy. Ischaemic optic neuropathy is a well recognised cause of sudden visual loss in middle and late life. It is characterised by painless visual impairment, pale swelling of the optic disc and nerve fibre bundle field defects. Although some cases are due to cranial arteritis, the majority of patients suffer from non-arteritic diseases, particularly hypertension. The present study consists of a reveiw of 22 cases of ischaemic optic neuropathy. Apart from cranial arteritis and vascular disease, migraine and trauma appear to have a causal relationship to the disorder.


Observations on voluntary nystagmus.

Observations on voluntary nystagmus. Unitl recent times, reports concerning voluntary nystagmus have been dismissive, most observers regarding the phenomenon as a form of ocular acrobatics or an amusing party trick. The introduction of sophisticated recording apparatus coupled with renewed interest in ocular kinetics has resulted in a more analytical approach. Clinical and electro-oculographic study of the condition in 5 subjects was undertaken in an attempt to relate voluntary nystagmus to the known mechanisms of oscular movement control. The frequency of the movement varied from 15 to 23Hz and amplitude from 2 to 5 degrees. The wave form was similar to that seen in acquired pendular nystagmus. It was concluded that, depsite differences in frequency, the similarity in form of the movements of voluntary nystagmus and acquired pendular nystagmus suggested a possible identity in the mechanisms of the movements.


Troxidone (trimethadione) embryopathy: case report with reveiw of the literature. It has long been known or suspected that phenytoin and probably phenobarbitone prescribed in pregnancy may lead to fetal malformations. The use of troxidone for epileptic women during pregnancy was reported in 1970 to lead to malformations. Over 50 instances of pregnancy in women taking troxidone have since been reported. In 8 of these the drug was used alone. 13 pregnancies resulted in abortion and 33 of the 40 survivors had a minor congenital anomaly, leading to death in 14. Complex congenital heart lesions with patent ductus, septal defects and aortic hypoplasia were apparent in half the survivors. Malformed or low-set ears were seen in nearly half the cases, palatal deformities were less common and evidence intrauterine growth retardation was frequently present. A 29-year-old mother taking troxidon and carbamazepine, and with a history of hypertension and proteinuria dating back to adolescence, delivered her first child prematurely. The child was small, showed deformed ears, displayed feeding problems and was found to be in cardiac failure with a systolic murmur and absent femoral pulses. Postnatal growth was retarded and after further cyanotic attacks a cardiac catheter study was performed. This showed a hypoplastic aortic arch with an anomolous origin of the left subclavian artery and patent ductus arteriosus, findings similar to those previously reported in neonates following maternal use of troxidone.


Two-dimensional echoencephalography in paediatric neurology. Two-dimensional echoencephalography is a useful procedure in screening young infants for hydrocephalus and cerebral malformation. The procedure is noninvasive and easily repeated. The procedure is less reliable in detecting mass lesions except insofar as they disturb the anatomy of the ventricular system. The procedure can be considered as complementary to computerised axial tomography in the investigation of cerebral anatomy in paediatric neurology.


Carbamazepine in two pregnancies.

Carbamazepine in two pregnancies. 2 patients with epilepsy in pregnancy are described. Both received carbamazepine prior to conception, and during the greater portion of the first trimester. Both had partial and generalised epilepsy of late onset. Case 1 resulted in stillbirth at 25 weeks' gestation. The malformations included closely set eyes, atresia of multiple hollow viscera, and non-fusion of the mandible without hare lip or cleft palate. A possible interaction with a compound analgesic is discussed. Case 2 resulted in a normal baby. The literature, although favouring carbamazepine in pregnancy, is not yet sufficiently decisive to indicate a clear preference between no treatment and carbamazepine with carefully monitored serum levels for epilepsy in pregnancy. This study emphasises the need for continued pooling of data, and for added caution when there is a history of fetal malformation or obstetric problems. The teratogenicity of carbamazepine is neither confirmed nor denied by this limited study.


Thoracic outlet syndrome secondary to childhood poliomyelitis. 2 women with acute anterior poliomyelitis affecting the upper limb girdles in early childhood later developed thoracic outlet syndromes, 1 of them bilaterally. It is thought that the poliomyelitis was a contributory factor in each case by allowing undue descent of the shoulder girdles, although cervical ribs were also present in the second case. This association had not been recorded previously. Both patients obtained substantial relief from anterior scalenotomy, indicating that previous involvement of the shoulder girdle by poliomyelitis does not negate the efficacy of this operative procedure.


Idiopathic scoliosis, scheurmann's disease and myopathy: two case reports. 2 cases of back curvature considered to be due to myopathy, but without associated limb weakness, are described. 1 case presented as infantile kyphosis with subsequent progression to scoliosis. There were some associated myopathic clinical features, including recurrent herniae and hip and knee contractures. The second case presented as an otherwise classical instance of Scheurmann's disease. Paraspinal muscle in both cases showed nonspecific abnormalities consistent with varieties of minimal change myopathy. EMG examination of limb muscles revealed myopathic abnormalities. These cases support the hypothesis that myopathy may underly some cases of apparently idiopathic scoliosis or kyphosis.


Computerised tomography in the leucodystrophies. 11 patients with a diagnosis of leucodystrophy are reported. In 9 the CAT scan was abnormal and showed areas of markedly decreased density in the white matter. 3 of these patients had adrenoleucodystrophy. In 2, contrast enhancement at the anterior borders of the low density areas was present. The 2 negative scans were from children with metachromatic leucodystrophy; one had an atypical form of the disease and the other had the biochemical defect, but was still presymptomatic and had no neurological deficit.


A retrospective study of carotid endarterectomy. 85 carotid endarterectomies were performed by the vascular unit at the Princess Alexandra Public Hospital between 1 July 1973 and 30 June 1978. The case histories of the patients undergoing the procedure were studied and the immediate mortality and morbidity associated with the procedure during the period were determined. 1 patient died following the procedure and 3.6% of operations resulted in a completed stroke. The indication for the operation, the referral source and the neurological condition of the patient undergoing the procedure were categorised in an attempt to determine the factors governing the selection of patients for this procedure. Excluding asymptomatic lesions, more than two-thirds of the operations were performed later than 2 weeks after the time of first referral to the hospital. Half the operations were performed after a delay of more than 1 month.


Familial trigeminal and glossopharyngeal neuralgia. A family incorporating 2 interesting variants of trigeminal and glossopharyngeal neuralgia is presented. The familial occurrence of these cranial neuralgias spanning 3 generations is very unusual. In the case of glossopharyngeal neuralgia it has not been documented previously. Furthermore, the coincidence of trigeminal and glossopharyngeal neuralgia in the same person is quite exceptional, despite the anatomical contiguity of the sensory territories of the fifth and ninth cranial nerves. These features suggest firstly that there must be an important constitutional factor in the aetiology of the cranial neuralgia, and secondly that in many cases there is a centronuclear rather than cranial nerve ganglionic pathogenesis of the pain.


Lipoma of the cauda equina: case report and review of the literature. Lipoma of the cauda equina is an uncommon condition, accounting for some 1% of spinal tumours. The literature is reviewed and the case is reported of a 41-year-old diabetic woman, who was seen in 1968 with a 37-year history of left foot deformity followed by left leg weakness and sensory loss resulting in a left below-knee amputation, with subsequent development of osteomyelitis and a chronic sinus, and of urinary incontinence and sensory loss in the right foot. A complete spinal block was evident below L3. Biopsy and limited removal of a portion of a lipoma of the cauda equina associated with considerable arachnoiditis was performed in 1967 and resulted in the disappearance of chronic back pain and cessation of faecal incontinence. There was partial restoration of bladder function and of perianal and left thigh sensation. This led to the patient being able to resume her household duties, and to visit friends and social functions after having been deprived of these pleasures for many years. Her condition has been well maintained since.


The stroke syndrome of long intraluminal clot with incomplete vessel obstruction. A stroke syndrome is described in 3 patients where long intraluminal clot formation with incomplete vessel obstruction was seen angiographically. The vessel involved in 2 cases were carotid arteries and in the third a vertebral artery. The intervening phase of long clot formation may be a feature of many cases of complete vessel occlusion. The common features of the syndrome were vessel tenderness (carotidynia in 2 cases, and vertebral artery tenderness in the third), vascular headache, the presence of subintimal haemorrhage as an anchor point for the clot, and the recurrence of clinical events. Surgical removal of these clots were successfully undertaken in each case at the acute stage.


Neuromyotonia in the spinal form of Charcot-Marie-Tooth disease. The term neuromyotonia has been applied to spontaneous activity of peripheral motor nerves which gives rise to pseudomyotonia, muscular fasciculations and myokymia. A family is described in which 8 members of 3 generations suffer from the spinal form of Charcto-Marie-Tooth disease (distal type of chronic spinal atrophy). 5 of the 8 members were examined and found to have myokymia, accentuated by voluntary muscle contraction. Pseudomyotonia was present in 2 patients and, in the 1 patient treated, was abolished by carbamazepine. The association between neuromyotonia and charcto-Marie-Tooth disease has been reported in only 7 patients before but may be more common than previously thought because muscle cramps are reported to be a feature of this disorder.


Contribution of single motor units to the surface electromyogram. McComas (1977) has published a method of estimating the number of motor units in human sketal muscle, based on peripheral nerve stimulation and recording of the surface electromyogram (EMG). One assumption of the method is that individual motor units, recruited by peripheral nerve stimulation just above threshold, give discrete observable increments to the surface EMG which are typical of motor units in the muscle. We have investigated this assumption in the thenar muscle. An EMG needle was inserted into the muscle and a series of individual motor units, activated voluntarily, was isolated. The discharge of these units was then used to trigger averaging of the concurrent surface EMG. Our results suggest that motor units activated by peripheral nerve stimulation close to threshold are not representative, in amplitude or timing, in their contribution to the surface EMG, of all motor units in the muscle.


The application of prolonged EEG telemetry and videotape recording to the study of seizures and related disorders. The clinical application of prolonged monitoring by the combined EEG and videotape recording of patients was evaluted. This test was found to be useful in diagnosing epileptic seizures in patients in whom both the history and diurnal EEG studies were unhelpful, and it assisted with the accurate classification of seizure types. It enabled seizure focus lateralisation in medically intractable epileptic who were being evaluated for surgery, and it also provided an objective estimate of minor seizure frequency. Prolonged EEG telemetry and videotape recording was especially useful in assessing additional seizures that develop in known epileptics. In some patients with syncope and drop attacks this technique helped to exclude atonic epileptic seizures and intermittent cardiac tachy-brady-arrhythmia as the underlying cause. As a method for identifying sleep disorders it has greater merits than conventional methods of polygraphic recordings.


Pathology and pathogenesis of chronic myelopathy in atlanto-axial dislocation, with operative or postoperative haematomyelia or other cord complications. Pathological features are described, and clinico-pathological correlations are made, in 11 patients presenting the unusual combination of chronic compressive myelopathy of the upper cervical cord due to congenital atlanto-axial dislocation, and sudden haematomyelia and respiratory arrest developing at open surgery for release of pressure on the medullospinal tissues, or as a postoperative catstrophe. Necropsy and histological examination confirmed that the neuropathological substrate of intermittent or progressive quadriplegia and sensory changes (mainly deep sensory loss) was degeneration of the lateral and posterior columns. Loss of anterior horn cells of the lower cervical and upper dorsal cord led to weakness of hand and arm muscles. Acute paracentral haemorrhages occurring at the C1 to C2 or medullospinal level, in the territory of distribution of the sulcal branches of the spinal artery (due to sudden release of pressure at operation) were responsible for postoperative paralysis and sensory loss below C2 segment. In terms of the bony anomaly (dissected at necropsy), the cases fell into 2 sibgroups:  a) The majority with the odontoid attached to the body of the axis, but short and ill developed, at times accompanied by other bony anomalies and a poorly formed transverse ligament. This tended to produce a fixed type of dislocation with a higher level (medullospinal) and more severe compression of the CNS. b) Fewer cases with a well formed but detached odontoid, producing a less severe myelopathy at a lower level (C1-C2), and generally more readily reducible on extension.


The epoxide of carbamazepine.

The epoxide of carbamazepine. Simultaneous steady-state plasma concentrations of carbamazepine and carbamazepine-10,11-epoxide have been measured by high pressure liquid chromatography in 101 epileptic children and adults taking the drug. There was either no statistically significant correlation, or only a very poor correlation, between drug dose and steady-state plasma levels of a) carbamazepine, b) its epoxide, and c) the sum of drug and epoxide. Plasma concentrations of carbamazepine correlated with those of it epoxide. Plasma carbamazepine levels were lower in patients taking phenytoin with carbamazepine than in patients taking carbamazepine alone. Plasma carbamazepine-10,11-epoxide levels were not definitely altered when carbamazepine and phenytoin were used together. This finding is consistent with the hypothesis that phenytoin enhances the metabolism of carbamazepine to a metabolite other than its epoxide.


Ultrastructure of nerve in erythema nodosum leprosum (ENL). Gross changes of myelinated fibres and Schwann cells at different degenerative stages were present in all five ENL nerve lesions. Besides these changes, infiltrating cells mainly macrophages, deposition of excessive collagen and perineurial vessel damage were also observed.


Ultrastructure of the haemocytes of Tetrodontophora bielanensis Waga (Collembola). Five types of haemocytes: prohaemocytes, plasmatocytes, granular haemocytes, spherule cells and phagocytes, have been distinguished on the basis of ultrastructural studies. Prohaemocytes are ovoid cells with a simple structural organization. Plasmatocytes are larger; their cytoplasm contains well-developed rough endoplasmic reticulum, numerous mitochondria and free ribosomes. Granular haemocytes are the most numerous of the blood cells, characterized by the presence of electron-dense granules. The cytoplasm of spherule cells contains many spherules made up of filamentous material of medium electron density. Rough endoplasmic reticulum, free ribosomes and mitochondria are also found in the cytoplasm. Phagocytes are the largest haemocytes. Their cytoplasm contains an abundance of lysosomes and myelin structures. In addition to haemocytes, cells intermediate between plasmatocytes and granular haemocytes have been observed, which indicates that the granular haemocytes are derived from plasmatocytes.


Ultrastructural study of yolk formation in Porcellio scaber Latr. (Isopoda). Two types of yolk are formed in the developing oocytes of a terrestrial crustacean, Porcellio scaber. The intra-oocytic yolk, arises through autosynthesis, and the extra-oocytic yolk, is derived from micropinocytosis. the so-called disc shaped bodies, which occur in large numbers within the cisternae of a branched system of endoplasmic reticulum, are precursors of the intra-oocytic uolk. Dictyosomes are not involved in yolk formation in this species. Thus, the vitellogenesis of Porcellio scaber occurs in a manner analogues to that described in the aquatic crustaceans, which indicates that environmental factors have relatively little effect on this process.


Morphological definition of a case of 'usual' interstitial pneumonia. A 61-year-old Caucasian female complained of shortness of breath, fever, and a period of rapid weight loss. After routine studies, the patient underwent an open lung biopsy in order to define the characteristics of the interstitial lung disease, and initiate appropriate therapeutic intervention. Typical fibrotic and cellular proliferation were evident in the parenchyma, as determined by standard light microscopy. However, in a correlated study using light microscopy of plastic embedded tissue, as well as scanning and transmission electron microscopy, a major proliferating cell type was identified as a type II pneumocyte. These cells were the predominant lining cells of the alveoli and clearly protruded into and limited available respiratory air spaces. The predominance of type II pneumocytes in the pathogenesis of certain respiratory diseases requires that a better explanation be sought for this phenomenon.


[Investigation of the allergens of colophony and its derivatives used in the manufacture of sticking-plasters (author's transl)]. Colophony and its derivatives play an important part in intolerances to sticking-plasters. Gas chromatography revealed resinic acids (derivatives) in numerous products of that kind, even in the so-called "hypoallergic" ones. The profiles of the resinic acids contained in some sticking-plasters that are sold in several countries under identic names, are rather different. The results of physicochemical analysis of Elastoplaste, the normal French product, and of a "hypoallergic" product, coincide with the results of allergologic studies.


[Behaviour of the hepatic glutathione (GSH) in the rat in continuous administration of hexachlorobenzene (HCB) (author's transl)]. Adult male Wistar rats were fed with a diet containing 0.05% hexachlorobenzene (HCB) over a period of at least 90 days. At intervals group of 4 animals each were killed and the GSH- and cytochrom P-450-content, the 7-ethoxycoumarin-deethylation activity were measured in the liver. At the same time the urinary porphyrin excretion was determined. After ten days a massive induction of the microsomal mixed function monooxygenase system could be demonstrated, whereas the porphyria (e.g. an increased excretion of urinary porphyrins) became manifest after 56 days HCB-exposure. At the same time (56th day of experiment) the GSH content in the liver rapidly decreased. It is assumed that at the beginning of th HCB-feeding the microsomal mixed function monooxygenase are induced and the uroporphyrinogen decarboxylase is inhibited. This inhibition causes an accumulation of highly carboxylated porphyrins in the liver. Later on (around the 56th day of HCB exposure) a hepatic GSH decrease leads to an increase of heavy metal ions and to a disturbance of the heme biosynthesis that means the manifestation of the HCB-porphyria.


[Therapy of morbus Bowen with 5-fluoro-uracil ointment (author's transl)]. A case of extensive Bowen's disease of the skin treated successfully with topical 5-fluor-uracil is described. the follow-up time at present is 18 months. The carcinoma in situ arose in a cicatricial area of the right lower leg after lewisite contamination in 1940.


[A contribution to the generalization of the Gompertz function]. SCHARF (1976) discusses various growth models. For the Gompertz function the differential equation (Formula: see text) is used. In words: the difference between relative growth rate and relative growth acceleration is constant. On the other hand, according to WENK (1973), the differential equation (Formula: see text) applies to the Gompertz function. It can be shown mathematically that (Formula: see text) applies in general. From Eq. (2) one obtains without trouble (Formula: see text). Therefore, the property leading to the Gompertz function may be defined as follows; the logarithmic derivation of the relative growth rate is constant. Eq. (2) is applicable only in special cases. It can be extended by assuming that c is not constant, but a function of time. In this way, a great number of growth functions can be found, which have to be regarded as model-based extensions of the Gompertz function.


[The fitting of an empirical, time-dependent direction component for vertical growth, represented by the example of the Scotch pine (Pinus silvestris L.)]. The object of this work is to offer to model of SLOBODA, who demanded 5 conditions on a model for the growth of trees. One equation satisfying this conditions is considered. The fitting is demonstrated by an example.


[The determination of the parameter of Bertalanffy's growth differential equations by means of nonlinear internal regression]. A short survey is given on various parameterized versions of the logistic law of growth and of Bertalanffy's growth differential equations. To examine the validity of these various growth expressions internal nonlinear regressions were performed, and the results of the calculations are presented. The body length growth of man within the embryonic development serves as examples of a growth process. The parameters in the differential equations will be adjusted to the course of the divided central differences calculated from means of measured values of this growth process.


[The fitting of various growth functions to the description of tree height growth]. Electronic computing renders possible new methods for determining parameters of functions of stochastic relations. PAUL (1975), for instance, published a FORTRAN-program for iterative non-linear regression for any function having an independent variable. Thus, optimum parameter values of a number of growth functions were determined on the basis of tree height development. Growth functions by RICHARDS (1959, according to v. BERTALANFFY 1941) and by SCHARF (1971) reach highest accuracy of fitting. If systems of growth curves are constructed, the elements of which differ by variation of a single parameter (e.g. height class fan), then the flexibility of multiparametric growth functions gets lost however.


[The description of growth course using a generalized logistic growth function]. For a quantitative description of measured growth courses the generalized logistic function will be used which is derived on the basis of the well-known logistic function of VERHULST. Numerical properties of this expression and possibilities for its computerized adjustment to measured courses are discussed. Examples of growth processes and their mathematical description by adjusted generalized logistic functions demonstrate the effectiveness of an ALGOL-program system for nonlinear approximation which is specialized to this function type. Especially the numerical improvement of approximation quality is demonstrated for expressions containing an absolute term in form of an also adjustable parameter.


[Mathematical models for calculating volume growth, represented by the yield tables for the principal wood-producing species of Czechoslovakia]. Methods for the construction of volume increment tables for stands on the basis of the volume mean stem are described. The volume increment of the stand (iv) is expressed by the equation (Formula: see text). The stem number of stands (N) is determined directly by 100% or representative enumeration. The mean annual increment (iv) is calculated with the aid of the regression function (Formula: see text) (v) being volume of mean stem and (t) age of stand. The relations (2) were derived for 5 tree species (spruce, fir, pine, beach, oak) from the data of the new Czechoslovak yields tables (1975). The mathematical model for the tree species spruce and pine was tested on the basis of empirical material collected by the Tharandt department of forest management an forest yield science (within the framework of joint research activities) and good results were obtained. The results should be regarded as provisional ones. Further tests are envisaged.


[The application of quantitative methods in experimental morphology]. Quantitative analysis has assumed great importance for describing and appraising evolutionary and involutionary processes. Measurements alone do not permit conclusions regarding the laws governing natural development. The elaboration of biologically meaningful mathematical models is necessary for such purposes. This paper shows how functions with a terms can be used to describe skull and body growth under normal and experimental conditions (frontal biped model in Rattus norvegicus Berkenhout as a biological model). A model consisting of a 2nd order homogenous linear differential equation with constant coefficients has proved to be biologically meaningful for describing skull length and breadth, and for the gross body weight. In order to study different growth rates in control and experimental animals we have calculated "confidence intervals" for the graphs of the special solutions of the general integral. This permits optimum validity although no mathematically precise interpretation can be given.


[The application of a dynamic feedback control model to the estimation of the expenditure-dependent growth plateauing in forest stands]. In addition to the time-dependent description of growth an expenditure-dependent parameter is necessary, with the help of which it is possible to interpret quantitatively the expenditure of economically motivated silvicultural measures in forest stands. The solution of a differential equation contains the desired expenditure parameter, the time-dependent and site-index-dependent courses of pine stands are discussed in this paper as normal and additional expenditure for obtaining an additional increment by fertilisation.


Angiopathic serum factor in perinephritic hypertensive dogs. To investigate the role of circulating humoral substances in the pathogenesis of increased vascular wall water and sodium concentration in experimental hypertension, rabbit aortic media explants were cultured in tissue culture medium supplemented (10-20%) with serum obtained from the same dogs (n = 7): 1) before the induction of hypertension; 2) after wrapping one kidney in silk (two-kidney perinephritic hypertension, 2-KPHT); and 3) after contralateral nephrectomy (1-KPHT). Cultures also were run with serum of sham-wrapped and then unilaterally nephrectomized normotensive dogs (n = 4). After 3 weeks of culture, the explants were harvested, and their water, sodium and potassium concentration was measured. Compared to the composition of explants cultured in prehypertensive serum, the water concentration of explants cultured in 1-KPHT and the sodium concentration of explants cultured in 2-KPHT and 1-KPHT serum were increased (p < 0.05). The water and electrolyte content of explants cultured in sera of sham-operated normotensive control dogs was the same regardless of the type of serum used, pre- or post-sham surgery or post-nephrectomy. The effects of serum from hypertensive dogs were not explained by variations in serum creatinine, sodium and potassium levels or in plasma renin activities. The experiments provide evidence for the role of serum factor(s) in the pathogenesis of abnormal vascular wall water and sodium concentration in experimental hypertension.


[Urinary tract infections in childhood (author's transl)]. The clinical symptoms of urinary tract infections (UTI) are only rarely an indication of the presence of the disease in childhood. Of decisive importance for the detection of UTI is an appropriate investigation to determine whether there is significant bacteriuria. Since in a significant proportion of cases of UTI in children there is underlying congenital anomaly or functional change in the urinary tract with stasis, and since surgical means of treatment are available today, diagnosis, i.e. at least radiological exploration, is essential. Approximately half the children with UTI are younger than one year at the time of diagnosis. In neonates, boys are more frequently affected than girls, whereas in older age-groups the incidence of significant bacteriuria (approximately 1.5%) and clinically relevant UTI or pyelonephritis is higher in females than in males. "Idiopathic" ("non-urologically induced") UTI is very seldom found in boys after infancy, and "asymptomatic bacteriuria" is largely confined to females. The "urethral syndrome" is probably caused by minor obstruction of the urethra and "bladder-sphincter dyssynergy". The fact that approximately nine of ten cases of UTI relapse in children are due to reinfection with a different pathogen has certain consequences for therapy. Prophylactic long-term medication is recommended during the phase after surgical correction of anomalies of the urinary tract.


[Chronic pyelonephritis in adults (author's transl)]. The frequency of chronic pyelonephritis is often overestimated. Chronic pyelonephritis is probably always a secondary disease in cases with obstructive changes in the ureters or other primary renal damage. The influence of chronic infection on the progression of renal insufficiency is still not well understood today. Underlying disease and infection should always be taken into consideration in the treatment of chronic pyelonephritis.


[Therapy of chronic respiratory tract diseases (author's transpl)]. Except in the case of exogenous allergic asthma, the therapy of chronic respiratory tract diseases must be predominantly symptomatic due to the polyaetiology and inhomogeneity of these diseases. Effective treatment of the main pathophysiological symptoms is important for the course and prognosis of the disease. These symptoms usually consist of hypersecretion, infection and bronchial obstruction. With the exception of "infective asthma", bronchial infections are not present at the onset of the illness. Such infections usually result as complications of a disease from which the patient is already suffering, and are essentially the consequence of disruption of the automatic clearance mechanism of the bronchial system and impairment of immunological defence against infection. The best form of therapy is that which is specifically directed at the individual bronchial infection for a period of two weeks. Permanent antibiotic prophylaxis is to a large extent obsolete today. In addition to treatment of bronchial infection, the removal of bronchial obstruction is also very important. Modern bronchospasmolytics are now among the most effective agents, provided the obstruction is actually "reversible". A low dose of oral corticosteroids - administered with caution - is justified should it not be possible to reduce pulmonary resistance to below the "dyspnoea threshold" of the patient.


[Hypersensitivity to antibiotics: Frequency, risks, cross-allergies (author's transl)]. The present paper gives a systematic review of the clinical manifestations of allergic reactions and the underlying immunological mechanisms. Attention is drawn to the relatively high proportion of cases of anaphylactic shock and serum disease related to the total number of cases of allergic reaction, and to the diagnostic techniques available for detection of sensitization towards antibiotics. Structural allergenicity is mentioned, using penicillin allergy as an example. The frequency of allergy to several antibiotics and the frequency of cross-reaction between penicillins and cephalosporins reported in the literature are discussed critically.


[Humoral defence against infection (author's transl)]. The importance of endogenous defence against infection for the success of antibiotic therapy is demonstrated using immune defect diseases as an example. The carriers of specific humoral defence against infection are the antibodies and the complement system. Acting either individually or in combination they result in neutralisation of toxins and viruses, an inflammatory reaction and the killing of pathogens. Humoral-cellular antibodies and the complement system play a role in phagocytosis, acting as phagocytosis-enhancing agents (opsonins). The possibility of interaction of antibiotic therapy and endogenous defence against infection is discussed.


[Cellular antibacterial immunity (author's transl)]. Facultatively intracellular bacteria (Mycobacteria, Brucellae, Listeria monocytogenes, Salmonella typhi etc.) may not necessarily be killed after having being phagocytosed by polymorphonuclear leucocytes or macrophages, cellular immunity having first to be built up. This results in the formation of specifically committed T-lymphocytes, which in turn release lymphokines after restimulation by homologous antigen. Under the effect of lymphokines, mononuclear phagocytes are chemotactically attracted to the site of infection, granulomas are formed and macrophages within the granuloma are activated. The granuloma represents the tissue reaction within which the interaction between facultatively intracellular bacteria and defence factors takes place. The experimental details underlying this concept are reviewed.


[Pharmacokinetics of cefaclor and initial therapeutical experience (author's transl)]. Twelve normal volunteers in the fasting state were given 1000 mg cefaclor, and the serum and urine concentrations over 8 h and 24 h respectively were measured. The average peak serum concentration was 34.6 +/- 7.8 mg/l, this value being reached after 65.2 +/- 11.1 min; the half-life was 42.5 +/- 8.3 min. In another six volunteers the absorption of 500 mg of 'cefaclor following administration in the fasting state and after a test breakfast was studied. The peak serum concentrations after administration in the fasting state were 16.1 +/- 3.2 mg/l, and after a meal 12.5 +/- 1.9 mg/l; the areas under the curve did not differ. The low recovery rate of cefaclor in urine observed in this series of investigations could be partly explained by the inactivation of the substance in urine. Cefaclor was administered therapeutically to 23 patients, most of whom were suffering from bronchopulmonary infections and chronic pyelonephritis. The results of therapy were good in four patients, satisfactory in 13 patients and unsatisfactory in three patients. Intolerance was rare.


[Assay of cefaclor in serum and urine (including stability test) using high pressure liquid chromatography (author's transl)]. Using high pressure liquid chromatography (reverse phase method) a study was made of the stability of cefaclor dissolved in sodium citrate buffer, normal serum and urine and stored for different periods of time at 4 degrees C and 37 degrees C. In sodium citrate buffer (pH 4.0) and in urine (pH 6.0) no appreciable loss of activity of cefaclor occurred at either 4 degrees C or 37 degrees C, even after longer periods of storage (up to 24 h). Serum containing cefaclor stored at 37 degrees C lost about 4% of the active cefaclor after 30 min, 13% after 1 h and 20% after 2 h; no cefaclor could be detected after 24 h. The loss was lower during storage of serum containing cefaclor at 4 degrees C, and after 24 h 60% of the initial concentration of active cefaclor was found. Using a lichrosorb-NH2 column, it could be demonstrated that after 24 h storage of serum containing cefaclor, only phenylglycine, but not amino-chloro-cephem-carboxylic acid or cefaclor was present. After oral administration of 1 g cefaclor, cefaclor was present in the serum and urine of adult volunteers and only small amounts of phenylglycine and amino-chloro-cephem-carboxylic acid.


[Therapy of bronchitis and bronchopneumonia in adults with cefaclor (author's transl)]. Sixty-two patients with bronchopneumonia or bronchitis were treated with cefaclor. In 42 patients (= 68%), the therapy was clinically successful. Of the patients who did not respond to therapy, cefaclor-resistant bacteria were found in the sputum culture of seven. Of the remaining 13 patients, ten suffered a secondary infection with cefaclor-resistant bacteria, and in three patients the pathogen found before therapy persisted, although sensitive to cefaclor on testing. In seven patients therapy was clinically successful although cefaclor-resistant pathogens were present before the start of therapy. In the entire group of patients investigated no increase of SGOT, SGPT, alkaline phosphatase, bilirubin, urea or creatinine was observed. In two patients alkaline phosphatase and SGOT increased slightly; in three patients SGPT increased slightly. On the other hand, in several patients initially elevated SGOT, SGPT and alkaline phosphatase activity decreased during therapy. Clinical side-effects were seen in two patients. In one patient with known penicillin allergy a pruritic exanthema developed; in the other patient, who had dermatitis herpetiformis, exacerbation of skin efflorescences occurred.


[Experience with cefaclor in the treatment of ear, nose and throat infections. Indications for cefaclor therapy (author's transl)]. The efficacy and tolerance of the new oral cephalosporin cefaclor was tested in 61 patients treated for a variety of moderate to severe ENT infections which were not expected to undergo a spontaneous remission without antibacterial therapy. The most frequently isolated pathogens were streptococci and Staphylococcus aureus. The dosage consisted of 500 mg cefaclor three times daily, and the treatment lasted between 4 and 43 days (average 14 days). In 35 cases, some of whom had already been treated unsuccussfully with another antibiotic, the results were very good. In 22 patients locally applied medicaments or surgery contributed to the good result. In four patients an unequivocal evaluation was not possible or therapy was not successful. The frequently noted rapid response to treatment with cefaclor was impressive. No relapses were recorded. In pharmacokinetic studies a cefaclor concentration of 2.8 mcg/g was obtained in the tonsils 90 minutes after oral administration of 1000 mg. Clinical examinations in 61 patients and a complete range of laboratory tests in 47 patients did not reveal any case of allergic reaction. One patient only complained of nausea and diarrhoea. In two patients temporary low grade thrombopenia and thrombocytosis respectively were observed. In several patients a slight transitory rise in transaminases was seen. Cefaclor thus proved to be an effective and well-tolerated antibiotic. Its indications in the treatment of ENT infections are discussed.


[Cefaclor in dermatological therapy (author's transl)]. Thirty patients suffering from bacteriogenic skin diseases were given cefaclor, in most cases simultaneously with classical external dermatological therapy. The results of therapy were satisfactory in 29 of the 30 patients. Only in one relatively severe case of erysipelas did the disease continue to spread despite the daily doses of 3 x 500 mg of oral cefaclor prescribed by the dosage regimen. Side-effects observed consisted of diarrhoea in one patient, and a transient slight increase of SGOT or alkaline phosphatase in another six patients.


[Investigations on the excretion of cefaclor in human bile (author's transl)]. The concentration of cefaclor in serum and bile was determined for up to 360 minutes after a single oral dose of 1 g cefaclor in 18 patients with continuous T-drainage of the bile duct. The rate of absorption varied, there being marked differences in the time. The peak bile concentration of 12.1 mcg/ml was reached after 120 min; the peak serum concentration of 12.3 mcg/ml, on the other hand, was reached after only 90 min. There was no accumulation of cefaclor in the bile.


Cefaclor: summary of clinical experience. Cefaclor, a new semisynthetic cephalosporin antibiotic for oral use, was studied by 62 clinical investigators in six countries in 1493 adult and paediatric patients. The pooled data reveal that satisfactory clinical responses were obtained in 80% of urinary tract infections, 87% of upper respiratory tract infections, 90% of cases of otitis media, 99% of lower respiratory tract infections, and 96% of skin and skin structure infections. Administration of this antibiotic was associated with a low incidence of adverse reactions including gastrointestinal (2.6%) and hypersensitivity (1.5%). Of particular clinical interest were the outstanding results obtained in the treatment of otitis media and lower respiratory tract infections.


Fate of the synthetic immunoadjuvant, muramyl dipeptide (14C-labelled) in the mouse. Synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide or MDP) represents the smallest unit that can substitute for whole Mycobacteria in Freund's complete adjuvant. In this paper the fate of 14C-labelled (on the muramyl moiety) MDP is reported. Following intravenous or subcutaneous injection into mice, more than 50% of 14C-MDP was recovered in the urine after 30 min and more than 90% after 2 h. The labelled compound was found unchanged in the urine, as shown by detailed analyses. However, MDP was sequestered for a longer time at the site of injection when administered as a water-in-oil emulsion. Considering the relatively rapid elimination observed, it is suggested that the biological effects of MDP and related compounds, when administered in an aqueous medium, may be due to their activity at minute concentrations and/or an immediate action at the cellular level.


Genetic and epigenetic control of levamisole-induced immunostimulation. Antibody responses to a T-cell dependent antigen, sheep red blood cells, were evaluated in mice of various inbred strains, treated or untreated, with levamisole. These responses appear to be under polygenic control, not associated with the H-2 complex, and modified by a Y-linked component and epigenetic factors revealed by aging. Strain, sex, age and the dose of levamisole all in influenced in an interrelated manner the activity of levamisole. Effects varied from inhibited to unchanged or increased antibody-forming cell numbers, without a direct relationship between the genetic regulation of levamisole effectiveness and a genotypic capacity to respond to the antigenic signal. Therefore, a complex relationship between host, antigen and immunopotentiator appears to be responsible for modifying the production of suppressor or helper influences. The present findings may serve as a warning against the uncritical use of levamisole.


Time in chemo-immunotherapy models: an absolute or a relative variable? Lessons from the levamisole experience. An analysis is presented of the findings from the available studies in several cancer models, where 2.5-20 mg/kg levamisole was given in combination with different types of cytostatic drugs. It appears that in chemo-immunotherapy experiments it may be preferable to measure time variables (increase in life span, timing of chemotherapy and of immunotherapy) as a per cent of the median survival time of the untreated controls instead of using time as an absolute measure (in days). As regards the study of levamisole in chemo-imnmunotherapy models, the increase in life span by the cytostatic alone seems to be the most important variable studied here. An "optimal" protocol for the evaluation of levamisole is proposed based upon all the findings of this analysis.


Differential potencies of corticosterone and hydrocortisone in immune and immune-related processes in the mouse. The effects of corticosterone and hydrocortisone on the thymus, the pituitary--adrenal axis, delayed hypersensitivity, the corticosterone plasma level and the numbers of circulating nucleated and monocytic cells were investigated in the mouse. Short-term effects within 48 h after one or two corticoid injections and late effects 7 days after a regimen of 4 corticoid injections were discerned. In short-term experiments hydrocortisone was more active than corticosterone upon the induction of leukopenia and monocytopenia and the inhibition of delayed hypersensitivity. However, regarding late effects and the short-term effect on adrenal weight, corticosterone far exceeded hydrocortisone in activity. Our results could be explained by assuming two feedback-inhibition systems for glycocorticoids. The first, likely to be responsible for the changes observed for the adrenal weight and the numbers of ciruclating white cells after a single glucocorticoid injection, was shown to be expressed in a soluble factor released in the blood stream tentatively designated "glucocorticoid inhibiting factor. The factor was more readily induced by hydrocortisone but displayed a greater specificity in inhibiting effects of corticosterone. The second feedback-inhibition system, responsible for increased numbers of circulating monocytes paralleled by an enhanced delayed hypersensitivity response, was expressed in a decreased corticosterone plasma level, most probably secondary to a diminished release of ACTH from the pituitary gland. With the glucocorticoid doses we used the second feedback-inhibition system was only triggered by the more physiological hormone, corticosterone.


Amphotericin B-induced immunosuppression in tumor-bearing mice. B16 melanoma-bearing mice had a reduced capacity to mount a delayed-type hypersensitivity response, and this response was further depressed when these mice were also treated with multiple daily doses of amphotericin B (AmB). Results from the present experiments, which were designed to simulate the clinical situation, indicate that patients receiving AmB may require frequent monitoring of immune functions during treatment.


Estimation of polymerization efficiency in the formation of polyacrylamide gel, using continuous optical scanning during polymerization. The Ferguson plot and 'quantitative' gel electrophoresis (based on the Ferguson plot) depend on a knowledge of accurate gel concentrations. The easiest way to estimate accuracy of gel concentrations, in terms of the degree of completion of the polymerization reaction which gives rise to a gel, is by spectrophometry. Making use of the apparatus for continuous optical scanning of polyacrylamide gels, the extent and rate of polymerization of cross-linked polyacrylamide were estimated by measuring the absorbance at 275 nm of the reaction mixture subsequent to free radical initiation of polymerization. Under appropriate conditions of monomer concentration, initiator levels and temperature, absorbance decreased monotonically after a lag period of 10 min, and after 20--30 min of reaction the absorbance reached a plateau value which provided a measure of polymerization efficiency. Application of a standard curve of absorbance vs. monomer concentration allowed one to quantitate concentrations of residual monomer throughout the course of polymerization. Under a set of arbitrary polymerization conditions (e.g. 6--20% total gel concentration), the reaction went to 63--96% completion. The rate of polymerization was approximately proportional to the square of the monomer concentration (2nd-order reaction kinetics). Absorbance decrease subsequent to the initiation of the polymerization reaction appeared suitable as a measure of efficiency of polymerization since: (a) absorbance spectra of monomers at 0.5 %T and residual monomers in a 10 %T gel, at a time when polymerization seemed terminated, coincided; (b) values of residual monomer obtained were reasonable (10--30%); (c) bimolecular reaction kinetics were found, in agreement with expectation; and (d) absorbance of incomplete polymerization mixtures, deficient in either initiators or monomers, was constant with time.


A simple Beckman DU accessory for location of proteins separated by isoelectric focusing in granulated gel layers: isolation of human serum very low density apolipoproteins C-II and C-III-1. A simple, low-cost gel layer scanner has been developed for the Beckman DU spectrophotometer. The gel scanner makes it possible to localize zones precisely after preparative isoelectric focusing of proteins in 2-mm thick Sephadex G-200 layers. Using the scanner after isoelectric separation of a mixture of human serum apolipoproteins C-III-1 and C-II, pure proteis could easily be obtained.


Deuterated iodoacetanilide: a covalent protein label for neutron scattering studies. A simple preparation of a deuterated alkylating reagent is described. Its reaction with the beta 93-SH groups of hemoglobin was used to illustrate the preparation of a protein derivative which contains 5 covalently attached non-exchangeable deuterium atoms at a unique locus on each beta chain.


Recovery of volatile fatty acids from biological materials for direct analysis by gas chromatography. A simple and efficient methodology for preparing aqueous extracts of volatile fatty acids from biological materials, for direct analysis by gas chromatography is described. Peak areas and responses relative to n-butyric acid were used to calculate concentrations of the individual acids. An example is given for analysis of the volatile fatty acids found in the blood of the lugworm Aerinocola marina.


Vitamin D-dependent calcium-binding protein. Changes during gestation, prenatal and postnatal development in rats. During the perinatal period, calcium metabolism is stressed. As intestinal Ca-binding protein is considered as a molecular expression of the hormonal effect of 1,25-dihydroxycholecalciferol (1,25(OH)2D3), Ca-binding protin measurements may document the vitamin D roles during this period. We describe the variations of Ca-binding protein concentrations in the rat during the last 5 days of gestation, in the maternal duodenum, placentas, fetal membranes and fetal intestines. We also report intestinal Ca-binding protein changes from birth until weaning. The evolution of the maternal intestinal Ca-binding protein, which increases on day 19.5 of gestation, is consistent with that of calcium intestinal absorption and may be explained by increased 1,25(OH)2D3 production. Placental Ca-binding protein rises from day 17.5 until the end of gestation, and may be related to the profile of calcium transfer from mother to fetuses. It is noteworthy that the placental Ca-binding protein is predominantly found in the fetal part of the organ where materno-fetal exchanges occur. The yolk sac synthesizes substantial amounts of Ca-binding protein. In the fetal membranes, Ca-binding protein plateaus from day 17.5 until day 20.5 and decreases on day 21.5. The Ca-binding protein presence in the fetal placenta and in the yolk sac may suggest that these tissues are also targets for vitamin D. In the fetus the intestinal Ca-binding protein s is detected as early as day 17.5 of gestation and increases markedly during the last day of gestation. From birth and during the first 3 weeks of postnatal life, the intestinal Ca-binding protein concentration does not change. It undergoes a sharp rise just at the time of weaning. We have also shown that the specific distribution of Ca-binding protein along the intestine is acquired during intrauterine life and does not change with sucking or weaning. The two main changes of intestinal Ca-binding protein, observed just before birth and at weaning, may reflect the intestinal maturation and/or variations in vitamin D metabolism.


Ventilatory responses to hypoxaemia during sleep in the newborn. Ventilatory responses to rapidly developing hypoxaemia during N2-rebreathing were compared for active and quite sleep in three newborn lambs and four puppies. In lambs, active sleep was associated with: (i) development of ribcage deflation during inspiration, which persisted during progressive hypoxaemia; (ii) depressed ventilatory response to hypoxaemia despite increments of respiratory rate; (iii) delayed arousal. In the puppies, inspiratory collapse of the ribcage did not occur in active sleep and the ventilatory responses during hypoxaemia were similar to those in quite sleep. While apparently defective when related to adults, these responses to hypoxaemia in the lamb are normal. This study illustrates the importance of considering behavioural state and species differences when studying the regulation of breathing, particularly during development.