Studies of the coagulation and complement systems during experimental Rocky Mountain spotted fever in rhesus monkeys.

We studied the coagulation and complement systems during Rocky Mountain spotted fever in Macaca mulatta experimentally infected with Rickettsia rickettsii. Ninety-one percent of monkeys infected intravenously with a high dose (10(6) plaque-forming units [pfu]) and 56% of monkeys infected with low doses (10(-1)-10(2) pfu) of R. rickettsii died after two to four days of illness. With the onset of fever and rickettsemia, animals developed hyperfibrinogenemia, mild thrombocytopenia, prolonged prothrombin and activated thromboplastin times, and increased serum fibrin/fibrinogen degradation products (FDP). Rickettsemia, thrombocytopenia, and FDP were greater in fatally ill monkeys than in survivors. Hemolytic titers of the second and third components of complement were not depressed except in a single surviving monkey that developed peripheral gangrenous ecchymoses at a time when both rickettsemia and agglutinating antibody were present. Thus, although activation and consumption of complement may occur during Rocky Mountain spotted fever, the hemostatic disturbances in fulminant infections seem to be a direct effect of the infectious vasculitis.


Purification of porcine and human ristocetin-Willebrand factor.

A plasmatic component required for the ristocetin-induced aggregation of platelets has been purified from normal human and porcine plasma by gel filtration (4% agarose) and anion-exchange chromatography (DEAE cellulose). No factor VIII coagulant activity was found associated with the purified human or porcine component. Urea sodium dodecylsulfate electrophoretic analysis of the purified component of both species indicated that the apparent molecular weight with intact disulfides is in excess of 500,000; after disulfide reduction with 2-mercaptoethanol, single components with an apparent subunit molecular weight of 230,000 were observed. Purified porcine ristocetin-Willebrand factor (RWF) co-sedimented in sucrose gradients with the factor present in normal plasma. Amino acid analysis of both human and porcine RWF indicated that all normal amino acids are present, whereas amino sugars were undetected. However, lipid analysis indicated 1% to 2% lipids present, including monoglycerides, di- and tri-glycerides, cholesterol, cholesterol esters, some free fatty acids, and a trace of phospholipid. A single line of identity was observed between normal human plasma and purified human RWF when immunodiffusion plates were run with purified rabbit anti-human RWF immunoglobulins. Antisera raised against human and porcine RWF's do not inhibit the factor VIII coagulant activity of the homologous plasma, nor is "spontaneously occurring" human factor VIII inhibitor neutralized by the isolated material of either species.


An in vitro measurement of bleeding time.

An in vitro method of measuring the bleeding time is described. The test, called the machine bleeding time (MBT), is not affected by heparin and detects the same types of hemostatic abnormalities as the template bleeding time. It is sensitive to thrombocytopenia, aspirin administration, and von Willebrand's disease. It is a reproducible test suitable for replicate and serial determinations and permits in vitro evaluation of the addition of drugs.


Radioimmunoassay of human plasma Lp(a) lipoprotein.

A quantitative immunodiffusion assay demonstrated Lp(a) lipoprotein in 91% (911 of 1000) of subjects. In order to quantitate Lp(a) in all plasma, a sensitive and specific double antibody radioimmunoassay was developed. The between-assay coefficient of variation was 8%. Lp(a) levels by radioimmunoassay were highly correlated with those obtained by the less sensitive radial immunodiffusion method (r = 0.98, n = 51). All but one of the 89 Lp(a) "negative" subjects by immunodiffusion had detectable levels of Lp(a) by radioimmunoassay. The one subject without detectable Lp(a) had abetalipoproteinemia (without detectable apolipoprotein B by radioimmunoassay). Furthermore, Lp(a) was detected in all three non-human primates examined: patas monkey, baboon, and pig-tail monkey. Quantitation of Lp(a) levels in 90 male myocardial infarction (MI) survivors and their spouses showed that the distribution of Lp(a) levels of MI survivors was significantly higher above the 50th percentile cut-point (P < 0.02) and exceeded that of the spouses. Furthermore, the Lp(a) distribution at and above the 50th percentile for the MI survivors who had an MI at age <50 (n = 36) was shifted to values higher than those having an MI at age >50. Thus, high levels of Lp(a) may be associated with premature coronary disease. We conclude that Lp(a) is present in all individuals with apolipoprotein B and that apolipoprotein B appears necessary for the plasma transport of the Lp(a) lipoprotein. Consistent with this hypothesis, quantitative immunochemical precipitation of (125)I-Lp(a) indicated that essentially all individual molecules of six purified Lp(a) preparations contain both the Lp(a) antigen and apolipoprotein B.


Quantitative analysis of plasma neutral glycosphingolipids by high performance liquid chromatography of their perbenzoyl derivatives.

A quantitative high performance liquid chromatography method for the analysis of neutral glycosylceramides as their perbenzoyl derivatives has been devised. Samples containing more than 2.5 nmol each of mono-, di-, tri-, and tetraglycosylceramide are benzoylated with 10% benzoyl chloride in pyridine at 37degrees C for 16 hr. The products are separated from excess reagents by solvent distribution and injected onto a pellicllar silica gel (Zipax) column (2.1 mm X 50 cm). The derivatives are eluted with a 10 min linear gradient of 2-17% ethyl acetate in hexane at 2 ml/min and absorbance at 280 nm is recorded. The detector response was proportional to the weight of sample used (2-30 nmol) and the lower limit of detection was about 70 pmol. The procedure has been applied to the quantitative analysis of erythrocyte and plasma glycolipids. As little as 0.5 ml of plasma can be used for analysis. The relative standard deviation of repetitive analyses ranged between 2.0% for glucosylceramide to 5.4% for galactosyllactosylceramide.


Sialic acid concentration in the reproductive organs, pituitary gland and urine of the Indian langur monkey (Presbytis entellus entellus).

The concentration of sialic acid was determined in the reproductive organs, pituitary gland and urine of male and female langur monkeys. In the male, sialic acid concentration was lowest in the testes and highest in the epididymides. Both caput and cauda epididymides contained almost the same concentration. Castration and subsequent androgen administration did not modify the concentration of sialic acid by comparison with intact animals, suggesting that sialic acid is not androgen-dependent in the langur. There was no significant difference in sialic acid concentration in the uterus during the proliferative and luteal phases of the menstrual cycle. After ovariectomy, there was a decrease in the concentration of sialic acid in the uterus, cervix and vagina while oestrogen or oestrogen plus progesterone administration increased its concentration significantly, but not to the control level. However, the difference in concentration between oestrogen-treated and oestrogen plus progesterone-treated monkeys was not significant. There was a peak of sialic acid excretion in the urine on day 8 of the normal 22-day menstrual cycle, i.e. a day before the probable day of ovulation. In pregnant monkeys siliac acid excretion increased significantly 2 days before delivery compared with the values recorded 7 to 3 days before parturition. The part played by sialic acid during the menstrual cycle and pregnancy in the female is not clear.


Steroids in the amniotic fluid of the rhesus monkey (Macaca mulatta).

Representative C21, C19 and C18 steroids have been measured in the amniotic fluid and maternal femoral plasma of rhesus monkeys during the last 50 days of pregnancy. The concentrations of cortisol, progesterone, androstenedione, oestrone sulphate all increased in amniotic fluid before spontaneous parturition. In contrast, amniotic fluid oestradiol levels remained low and unchanged, and were always less than the concentrations in the maternal plasma. The changes in progesterone, cortisol and oestrone concentrations in amniotic fluid occurred independently of significant changes in the concentration of these steroids in the maternal plasma. Betamethasone administered to monkeys after day 150 of pregnancy suppressed amniotic fluid and maternal plasma cortisol. This treatment markedly suppressed the concentration of progesterone in amniotic fluid, but did not alter its concentration in maternal plasma. It is concluded that during late pregnancy in the rhesus monkey there is an increase in the concentration of some steroids in amniotic fluid independent of alterations in their concentrations in maternal plasma. These changes could reflect an increase in foetal adrenal steroid secretion.


Analysis of a newly-isolated temperature sensitive maternal effect mutation of Drosophila melanogaster.

A mutation located near the tip of the X chromosome in Drosophila melanogaster has been isolated, and its developmental effects described. This mutation (1(1)ts-1 is temperature sensitive, and at permissive temperature (18 degrees C) develops normally. However, zygotes from females raised or aged at restrictive temperature (28 degrees C) never hatch, regardless of the embryonic genotype. Midgut formation is abnormal in lethal zygotes and dorsal closure is probably incomplete. Temperature shift experiments have shown that the zygotic lethality is governed by a temperature sensitive period in oocytes of stage seven or older. If viable 1(1)ts-1 embryos are shifted to restrictive temperatures, they develop as far as the pupal stage, but never eclose. The temperature sensitive period for pupal lethality includes the last 2.5 days of pupal development and does not involve a maternal effect.


The role of cortical pattern in timing of cell division and morphogenesis in Stentor.

This paper describes experiments involving reciprocal exchange of the oral apparatus between a large (L) and a small (S) strain of Stentor coeruleus. Mature L-strain stentors given and S-strain oral apparatus formed an oral primordium in response to the presence of abnormally small oral structures and mostly divided although a few reorganized instead. Conversely, when S-strain stentors in early division were given a large L-strain oral apparatus, they resorbed the developing primordium and returned to interphase. When combined with previous results, these findings provide evidence for the hypothesis that the time of cell division in Stentor is determined by a "critical" ratio between the size of the oral apparatus and the size of the cell body (somatic) cortex. This ratio develops because the somatic cortex grows during interphase and the oral apparatus does not. Cell division in Stentor therefore appears to be initiated by a cortical pattern change resulting from cell surface growth during interphase.


Catabolism of L-lysine by Pseudomonas aeruginosa.

Pseudomonas aeruginosa PACI grows poorly on L-lysine as sole source of carbon but mutant derivatives which grow rapidly were readily isolated. Studies with one such mutant, P. aeruginosa PAC586, supported the existence of a route for L-lysine catabolism which differes from those reported previously in other species of Pseudomonas. The postulated route, the cadaverine or decarboxylase pathway, is initiated by the decarboxylation of L-lysine and involves the following steps: L-lysine leads to cadverine leads to I-piperideine leads 5-aminovalerate leads to glutarate semialdehyde leads glutarate. Evidence for this pathway is based on the characterization of the pathway reactions and the induction of the corresponding enzymes by growth on L-lysine. The first three enzymes were also induced by growth on cadaverine and to a lesser extent by 5-aminovalerate. No evidence was obtained for the presence of pathways involving L-lysine 2-monooxygenase or L-pipecolate dehydrogenase, but another potential route for L-lysine catabolism initiated by L-lysine 6-aminotransferase was detected. Studies with mutants unable to grow on L-lysine supported the existence of more than one catabolic pathway for L-lysine in this organism and indicated that all routes converge on a pathway for glutarate catabolism which generates acetyl-CoA. Pipecolate catabolism also appeared to converge on the glutarate pathway in P. AERUGINOSA. The results suggested that the growth rate of the parental strain is limited by the rate of transport and/or decarboxylation of L-lysine. The cadaverine pathway was present, but not so highly induced, in the parental strain P. aeruginosa PACI. Pseudomonas fluorescens contained enzymes of both the cadaverine (decarboxylase) and oxygenase pathways, strains of P. putida (biotypes A and B) contained enzymes of the oxygenase pathway but not the decarboxylase pathway and P. multivorans appeared deficient in both. All these species possessed L-lysine aminotransferase activity.


Morphological characteristics of acetylcholinesterase-containing neurons in the CNS of DFP-treated monkeys. Part 2. Diencephalic and medial telencephalic structures.

The distribution and morphological characteristics of neurons containing acetylcholinesterase (AChE, EC 3.1.1.7.) in diencephalic and medial telencephalic structures of the rhesus monkey (Macaca mulatta) were studied by means of a pharmaco-histochemical method that involves staining for AChE (Karnovsky-Roots' procedure) at various times after the administration of di-isopropylfluorophosphate (DFP). At medial telencephalic levels, numerous, mostly multipolar, AChE-containing neurons of medium to large size are present in the bed nucleus of the anterior commissure, in the ascending division of the nucleus of the diagonal band of Broca, and in the so-called "substantia innominata". This last structure is composed of medial and lateral AChE cell  groups that extend caudad, beneath the lenticular nucleus, for a considerable distance. The AChE neurons lying within the substantia innominata correspond, at least in part, to the basal nucleus of Meynert. Most neurons of the olfactory tubercle are devoid of AChE but lie within a lightly-stained AChE background. In addition, clusters of amorphous and highly reactive AChE material are found within the islands of Cajella and along the ventromedial edge of the olfactory tubercle. At the level of the thalamus, the strongest AChE staining is seen in the periokarya of the anterior dorsal nucleus and of most nuclei located within the fibrous or lamellar thalamic structures--i.e., the reticular nucleus, the intralaminar nuclei, and the midline nuclei except nuclei parataenialis and reuniens. In most of these nuclei the neuronal somata are of medium size and stain moderately for AChE. Their proximal processes are either lightly stained or devoid of AChE. At the level of the hypothalamus of the monkey, intense AChE staining can be seen within the neuronal somata of the supraoptic and paraventrivular nuclei. In the paraventricular necleus, the AChE-positive perikarya are of medium size and have numerous AChE-containing processes. Moderately reactive AChE neurons of smaller size with unstained processes are also present in the paraventricular nucleus. Most perikarya of the main rostral portion of the supraoptic nucleus are moderately stained for AChE, are closely packed, and their processes are difficult to discern. The main cellular aggregate of the supraoptic nucleus extends caudad and is composed of a large group of moderately to intensely stained neurons lying along the optic tract and which constitute the caudal, or infundibular, portion of the supraoptic nucleus. Other moderately to intensely stained AChE neurons were found in the lateral and perifornical areas and most particularly in the dorsal hypothalamic area. These neurons are of medium size and mostly multipolar. Moderately stained AChE neurons were also observed in the supramammillary nucleus, as well as those of the acruate nucleus, however, are only weakly reactive. The median eminence and most neurons of the ventromedial nucleus of the monkey hypothalamus are virtually devoid of AChE...


Absence of vasospastic response of the anterior spinal artery to subarachnoid blood.

Autologous blood (0.3 to 5.0 ml) was introduced into the lumbar subarachnoid space of nine monkeys. Serial spinal cord arteriography was performed at frequent intervals over a 24-hour period. Magnification techniques permitted direct measurement of the anterior spinal artery and posterior spinal vein. Neither immediate nor delayed spasm was observed in any animal. Similar techniques have routinely produced spasm of intracranial arteries in our laboratory.


Multiple meningeal diverticula and cysts associated with duplications of the sheaths of spinal nerve posterior roots.

Multiple diverticula and cysts of the meninges were found during an anatomical dissection. They were associated with duplications of sheaths of the posterior roots of the spinal nerves. The diverticula and cysts appeared as simple flaccid corrugated dilatations of the sheaths, as ampullary expansions, as pediculated cysts, or as saccular dilatations of different sizes and locations. The duplication of the sheaths affected posterior roots of the thoracic nerves only. Some variations of the sheaths described in the literature are discussed. The possibility is considered that both conditions result from the same pathological factors in the embryo.


Effect of protein-energy malnutrition on the growth of mandible and long bone in newborn male and female rats.

Several parameters were measured in the growth centers of mandible and long bone of rat pups suckled on dams fed 25% or 6% protein diets. No sex-related differences were found in any parameter either during normal growth or in response to malnutrition. While the total contents of protein, DNA, RNA and calcium were reduced in both tissues, mandible was less affected than long bone, although it appeared to be affected earlier. Moreover, malnutrition reduced the number of cells in the mandible without changing cell size or calcium content. In contrast, long bone appeared to be affected later than mandible, and to be modified differently. In this case, not only cell number, but also cell size and cellular content of calcium were reduced. The results can be interpreted to mean that the critical periods of growth for mandible and long bone are different. Moreover, some suggestion of differences in relative sensitivity to malnutrition of these two hard tissues was also observed.


Pulpal response to pyruvic acid.

Etching of enamel surfaces produces a marked increase in the bond strength of dental materials to tooth structure. The results of recent studies have indicated that pyruvic acid may be used in preference to phosphoric acid, because of its milder etching effect on enamel surfaces, without adversely affecting the bond strength. The pulpal responses elicited by 10% pyruvic acid applied for 90 seconds to freshly prepared cavities in monkey teeth, were examined after 4, 14 and 42 days. The differences between some of the ariteria used to evaluate the pulpal responses in acid-treated and control teeth at the three post-operative time intervals were statistically significant. These results suggest that exposed dentin should be protected with a lining before etching adjacent enamel surfaces with 10% pyruvic acid.


Arterial blood pressure in patients with oral lichen planus.

The arterial blood pressure of 121 patients with oral lichen planus was determined using the auscultatory method. These values were then compared with those previously found in a general adult population. No significant difference was found betwween the values of the lichen planus patients and those of the general population. The present investigation does not support the hypothesis of a relationship between lichen planus and hypertension.


Glucose tolerance in patients with oral lichen planus.

Of 123 patients with oral lichen planus two were known diabetics. The remainder were tested for fasting glucosuria, 113 for fasting blood glucose and 103 also with an oral glucose tolerance test. According to the criteria of WHO, 18 of the 123 patients were diabetics. In most of these patients the oral glucose tolerance test was only slightly abnormal. No decrease of the glucose tolerance with increasing duration of lichen planus was demonstrable. Comparison with two general population studies did not reveal any significant difference between the glucose tolerance of the lichen planus patients and that of the general population samples.


The effects of length of surgery on healing of full and partial thickness flaps.

Partial and full thickness flaps which were were made in the facial gingiva of 10 dogs were reflected for 15 or 90 min. Specimens were examined histologically and biochemically from 3 to 28 days after initial surgery. The results indicate that flaps refelected for 15 min exhibited faster epithelial closure than those reflected for 90 min. Partial thickness flaps reflected for both 15 and 90 min showed less inflammation than full thickness flaps at 3 and 7 days post surgery and healed faster in respect to epithelial closure, mesenchymal healing, and bone regeneration. Biochemical analysis of the collagen concentration of the tissure flaps revealed similar collagen content in full and partial thickness flaps reflected for 15 min; however, the collagen concentration of partial thickness flaps opened for 90 min was higher than that in full thickness flaps.


Studies on the invasive ability of malarial merozoites (Plasmodium berghei).

Studies were performed to evaluate several methods for the artificial removal of Plasmodium berghei merozoites from infected mouse erythrocytes. These methods, many of which have been reported to yield free parasites capable of establishing a patent infection when injected into a suitable host, included NH4C1-mediated lysis, complement-mediated immune lysis, pressure filtration, and multiple-burst and continuous-flow sonication. Free parasites isolated from infected mouse blood were examined in vitro under conditions known to support merozoite invasion, and were found to be noninvasive, irrespective of the method used for their isolation. Although all methods tested achieved high degrees of lysis, none removed all intact parasitized erythrocytes. Using multiple-burst and continuous-flow sonication, the infective potential of free parasite preparations could be accounted for solely on the basis of the intact parasitized cells contaminating the free parasite preparations.


Sarcocystis fayeri sp. n. from the horse.

Hearts, diaphragms, esophagi, and spinal cords from 266 horses were obtained at slaughter in Creston, Ohio. Tissues were examined microscopically for Sarcocystis in sections, digested in trypsin to obtain bradyzoites, and fed to 10 dogs and 10 cats. Intramuscular cysts were found in selections of two hearts from 57 horses and four esophagi from 107 horses. The cysts were up to 900 micron long and up to 70 micron wide. The cyst wall was 1 to 2 micron thick and cross-striated. The enclosed bradyzoites were banana-shaped, 15 to 20 by 20 to 3 micron, and contained several PAS-positive granules. Bradyzoites were found in trypsin digests of seven of 57 (13%) equine tissues (heart, diaphragm, esophagus but not spinal cord) in one experiment and 10 of 47 (21%) esophagi, eight of 47 (17%) diaphragms but none of 47 hearts and spinal cords in another experiment. All of 10 dogs shed sporulated sporocysts or oocysts in feces 12 to 15 days (12 in one, 13 in eight, and 15 days in one) after digesting tissues from 169 horses. The sporocysts were 11 to 13 (12.0 +/- 0.5) by 7 to 8.5 (7.9 +/- 0.5) micron. In histologic sections of canine small intestine the sporocysts were located in the lamina propria near the tips of the villi. The 10 cats fed tissues from 266 horses did not shed Sarcocystis. A new name, S. fayeri, is proposed for this organism. Sarcocystis fayeri sporocysts (12 by 8 micron) are shorter than those of S. betrami (15 by 10 micron), the other species of Sarcocystis from the horse. The prepatent period is 12 to 15 days for S. fayeri and 8 days for S. bertrami (synonym S. equicanis Rommel and Geisel 1975).


Investigations of the analgesic and morphine-like properties of azidomorphine.

In equianalgesic doses, azidomorphine is reported by J. Knoll, S. Fürst and K. Kelemen (The pharmacology of azidomorphine and azidocodeine. J. Pharm. Pharmacol. 25: 929-939, 1973) to be less likely than morphine to cause physical dependence. As the separation of the analgesic from the dependence-producing properties would represent an important contribution to the development of potent analgesic drugs, we have compared the effects of azidomorphine and morphine in a number of experiments in laboratory animals. In analgesic studies, azidomorphine was more potent than morphine in all tests and by every route of administration. However, the differences between the analgesic effects of azidomorphine and morphine were much smaller after oral than after parenteral administration. In the rhesus monkey, the programmed administration of azidomorphine over a period of 9 weeks produced physical dependence. In addition, azidomorphine was self-administered by the rhesus monkey over 3 weeks producing marked opiate-like physical dependence. It is concluded that the introduction of the azido group into the morphine molecule leads to a marked increase in analgesic activity compared with the parent drug but which does not decrease the ability to produce physical dependence.


Long-term behavioral changes in the rhesus monkey after multiple daily injections of d-methylamphetamine.

The effects of multiple daily injections of d-methylamphetamine on spaced lever-press responding were investigated in the rhesus monkey. Responding was measured after single injections of d-mehtylamphetamine (0.0625-1.0 mg/kg) both before and after the monkeys were maintained on a multiple daily d-methylamphetamine injection regimen in doses ranging from 0.5 to 16 mg/kg/day. Tolerance developed to the suppressant effects of this drug on responding. As evidenced by a shift in the dose-response curve measuring number of responses and number of reinforcements per session, this tolerance persisted for at least three months after cessation of the multiple drug injection regimen. In order for tolerance to develop, it was necessary for the animals to perform the task while maintained on drug. When saline was substituted for d-methylamphetamine, no evidence of a withdrawal syndrome was seen.


Testing of pit and fissure sealants in the monkey.

A pilot study was conducted employing the Macaca speciosa monkey to determine the retention and sealing ability of pit and fissure sealants in vivo. Several problems were encountered in the use of this animal model for this type of evaluation. Without doubt, the conditions to which the sealants were subjected in the monkey were more rigorous than those found in man. This is attested to by the lower rate of retention of sealants as compared to that found in studies on human beings. To increase the usefulness of animal studies of this type, additional research should be done to better establish the correlation between the behavior of sealants in the animal and in man. Nevertheless, certain pertinent observations were made, one of which is that in some instances where the sealant was retained on the teeth, the sealant-tooth interface was readily penetrated by an isotope solution.


[Ultrastructural characteristics of the cortex and of the membranelles of the ciliate Espejoia mucicola (Oligohymenophora, Hymenostomata, Tetrahymenina)].

It was shown in a detailed study of the cortex and buccal organelles of Espejoia that, at the ultrastructural level, the general plan of organization of this ciliate conforms to that of Tetrahymenina. Specific variations seen in the cortex and membranelles bring out the very pronounced affinities of Espejoia to the genus Glaucoma and other related ciliates. In view of the foregoing and on the basis of reccent findings on morphogenesis, we confirm the taxonomic position of Espejoia mucicola among Tetrahymenina in the family Glaucomidae.


Cortical ultrastructure of the Scuticociliates Dexiotricha media and Dexiotricha colpidiopsis (Hymenostomata).

Cortical ultrastructure of the scuticociliates Dexiotricha media and Dexiotricha colpidiopsis was investigated. The following elements of the somatic cortex were studied: the cell membrane, alveolar membranes and the epiplasm, kinetodesmal fibers, postciliary and transverse microtubular ribbons, and transverse fibers associated with single and paired kinetosomes; mitochondria and single microtubules located in interkinetal ridges; mature and early extrusion stages of mucocysts; the expulsion vacuole pore and tube, the nephridioplasm and the cytoproct. In the buccal cortex, the paroral kinety-ribbed wall complex, the 3 polykineties, and the cytostome-cytopharynx were investigated. Comparative survey of ciliate ultrastructure indicates 2 principal orientation patterns for kinetodesmal and postciliary fibers, recognition of which leads to reevaluation of the theory of paroral kinety formation and the ideas of homology based on this theory. Ultrastructurally, the scuticociliates are not distinct from tetrahymenines and peniculines; the 3 groups appear to be 1 assemblage.


Scanning electron microscopy of budding and metamorphosis in Discophrya collini (Root).

Budding and metamorphosis in the suctorian ciliate, Discophrya collini, have been investigated by scanning electron microscopy. The adult body form, tentacles, stalk, and attachment disk are described. A field of depressions or small pits was observed in the pellicle of adult suctorians in the early stages of bud formation. These pits deepen and coalesce until one large pore, the birth pore, remains. Cilia protrude through the pore, and as eversion of the bud proceeds the meridional arrangement of the larval ciliation is evident. After eversion is completed, a pronounced division furrow is found between the adult and soon-to-be-released swarmer. The stalk-forming region is seen on swarmers. Metamorphosing swarmers produce tentacles upon settling before any indication of ciliary resorption. Resorption of cilia and change in body form occur progressively with the production of the attachment disk and stalk.


Stomatogenic events accompanying binary fission in Blepharisma.

Stomatogenesis was studied in the heterotrich ciliate Blepharisma japonicum stained with protargol. During binary fission not only is a new oral apparatus made for the posterior daughter, but the already existing oral apparatus of the parent cell is reorganized, i.e., partially disassembled and then subsequently reassembled to provide a functional feeding apparatus for the anterior daughter cell. These morphogenetic events, requiring 2 1/2 to 3 hr, are complete by the time the anterior and posterior daughters separate. In preparation for division, an oral anlage is formed by the rapid proliferation of kinetosomes along 4-5 stomatogenic kinetics directly subtending the cytostome. This field of randomly oriented kinetosomes ultimately gives rise to the feeding apparatus of the posterior daughter cell. Early in division, the oral anlage separates into 2 longitudinal fields of kinetosomes: one is destined to give rise to the undulating membrane and the other forms the adoral zone of membranelles. Shorly after the anlage is established posterior to the cytostome, reorganization of the existing functional mouth is initiated. The morphologic changes associated with this dedifferentiation-redifferentiation sequence lead to the formation of an oral apparatus for the anterior daughter and cannot be distinguished from those characteristically seen during physiologic reorganization.


Qualitative and quantitative studies on DNA and RNA synthesis in Loxodes striatus nuclei.

In this study the characteristics of the synthesis of DNA and RNA in the nuclei of Loxodes were investigated. Loxodes striatus is a primitive ciliate with 2 pairs of structurally differentiated diploid nuclei, the macro- and micronuclei. The macronuclei and differentiated morphologically into a clearly recoginzable central core and an outer zone. To determine DNA and RNA synthesis, individual organisms were analyzed by autoradiography after incubating groups of cells with a 3H-labeled precursor ([3H]thymidine for DNA and [3H]uridine for RNA). The following observations were made: (A) All portions of macro- and micronuclei appeared to contain DNA as judged by the localizations of incorporated [3H]thymidine. (B) The macro- and micronuclei did not synthesize DNA at the same time; moreover, the duration of DNA synthesis in the former was much longer than of the latter nucleus. (C) Replication of DNA in the inner core and outer zone of the macronucleus occurred at separate times with little if any overlap. (D) All of the detectable [3H]uridine incorporation was found in the macronucleus and none in the micronucleus. Within the macronucleus the central core was more heavily labeled. (E) The quantitative differences in the label of the different components synthesis can occur in adult macronuclei. The possible explantion of these results is discussed in the context of the nuclear evolution of ciliates and of recent information on nuclear differentiation.


Cytotoxicity of synthetic fuel products on Tetrahymena pyriformis. I. Phenol.

Phenol is the major organic constituent of coal-conversion scrub water and is therfore a potential environmental contaminant. After Tetrahymena pyriformis strain GL-C, syngen 1 was exposed to phenol, its behavior, cytology, respiration, and growth rates were examined. Concentrations larger than or equal to 75 mg/liter alter cell motility, shape, and contractile vacuole activity. O2 uptake was abruptly reduced within 3 min of exposure to phenol in concentrations as low as 10 mg/liter. Concomitantly there was an increase in the electron density of the mitochondrial matrix. Recovery to normal rates of O2 consumption was paralleled by a return to normal matrix density. Alterations of mucocysts, pellicle, and glycogen were also observed. The length of lag phase growth curves increased generally in proportion to concentration of toxicant. Phenol, however, did not affect the rate of cell multiplication during the exponential growth phase. The potential use of this system to examine the effects of other possible organic pollutants is discussed.


Regulation of ciliary pattern in ciliates.

The modes of pattern regulation found in the ciliates Dileptus and Paraurostyla are compared. These forms are systematically distant but both possess very extensive regenerative capacities. They are characterized by 2 types of ciliary patterns: the ciliature of Dileptus has largely a simple pattern composed of single kinetosomes while that of Paraurostyla has a complex pattern composed of aggregates of kinetosomes interconnected by amorphic matter. In both ciliates a change in cell size evokes pattern regulation which differs substantially in the extent of pattern replacement, timing, and localization of morphogenetic activities. It is concluded that these differences result from the pattern constituents.


Molecules and morphologies: the perpetuation of pattern in the ciliated protozoa.

Three apparently conflicting generalizations concerning the relationships between molecules and cell structure may be derived from studies on cellular patterning in the ciliates. (A) Cells with identical genes and molecular composition may have different hereditary patterns. (B) Genes, through their prescribed molecular derivatives, constrain the modes of pattern permutation and define the states of greatest stability. (C) Cells with identical hereditary patterns may have entirely different genes and molecular compostitons. These priniciples may be reconciled through the recognition that they are characteristically applicable over different time intervals. Hereditary differences within a clone and without related molecular differences (principle A) may persist for hundreds of cell generations, but they are resolved eventually within a constant environment (principle B) as the configuration of minimal free energy is approached. On an even longer time scale, molecular substitutions have occurred for many or most components of the cell, but these have been constrained by selective pressures on an ancient design (principle C) that disallow substitutions affecting certain form-function relations which have been elevated to an adaptive peak.


Revision and checklist of the species (other than lecudina) of the aseptate gregarine family Lecudinidae.

A checklist is given of the 89 named species of the gregarine family Lecudininae, exclusive of the 42 named species of the genus Lecudina (phylum Apicomplexa, class Sporozoea, subclass Gregarinia, order Eugregarinida, suborder Aseptatina). The list includes also the synonyms, host names, locations in hosts, known geographic distributions of the species, as well as key references. Another list is given of synonyms, lapsi calami, nomina nuda, etc., associated with the genera. A new genus, Paraophioidina g.n., with type species, Paraophioidina haeckeli (Mingazzini, 1891) and a new species, Lankesteria ormieresi sp. n., are described. There are also new combinations in the genera Bhatiella, Ancora, Monocystella, Ascocystis, and Paraophioidina.


Nosema parkeri sp. n., a microsporidan from the argasid tick, Ornithodoros parkeri Cooley.

Nosema parkeri sp. n. is described from nymphs and adults of the argasid tick, Ornithodoros parkeri Cooley, from a laboratory colony. Schizogonic and sporogonic stages are described from various tick tissues. Spores are binucleate, measuring 3.2 (3-4) x 1.9 (1.8-2.5) micronm. Transmission is transovarial and transstadial. The parasite does not appear to affect adversely the development or reproduction of the tick. Dermacentor andersoni Stiles was experimentally infected. Attempts to infect Swiss mice by tick feeding or by injection of infected tick suspensions were unsuccessful. The microsporidan differs in structure from Encephalitozoon ixodis Weiser) and Nosema slovaca Weiser & Rehácek, the only other microsporidans known from ticks.


[Chronology of the ultrastructural modifications during the growth of Gregarina blaberae].

In an ultrastructural study the development of the sporozoite as well as the growth and development of the trophozoite of Gregarina blaberae were followed in the course of experimental infections of larvae of the cokroach Blaberus craniifer. The spectacular growth involved the transformation within 18 days of the sporozoite, measuring 15 X 1 micronm, to a cephaline--trophozoite affixed to the intestinal epithelium--of 250 micronm length and 65 micronm diameter. The sporozoite's ultrastructure is not different from that of sporozoites of other Sporozoa studies to date--the conoid and dense bodies are present. The pellicle consists of 3 membranes, but there are some interruptions in the internal membrane complex. The first dictyosomes are formed from the nuclear envelope. The migration of the nucleus and of the dense bodies, followed by the regression of all the structures characteristic of the sporozoites, and the establishment of a cortical zone that comes to cover the epimerite, take place within 48 h after infection and mark the transformation of the sporozoite into the trophozoite. Development of the cephaline involves the formation of the epicytic folds, which occurs at the base of the deutomerite, starting on the 3rd day of development. A regular system of longitudinal or epicytic folds is formed over the entire surface of the gregarine. On the 4th and 5th days of development, a vacuolar system and a chondriome become differentiated in the epimerite, while a fibrillar septum separates the protomerite from the deutomerite. The next stage, starting on the 6th day, is characterized by distribution of polysaccharide reserves between these 2 segments. The model studied allows us to determine the role of the epimerite in the parasite's nutrition, as well as the development of the chondriome and of the cortical membranes in the course of the vegetative growth phase of the cephaline gregarine.


[Ormiersia carcini gen. n., sp. n., microsporidian of the Mediterranean crab, Carcinus mediterraneus Czerniavsky, 1844: developmental cycle and ultrastructural study].

A microsporidan parasite, Ormieresia carcini gen. n., sp. n., was found in the crab, Carcinus mediterraneus Czerniavsky. Its development and fine structure are the subject are the subject of the present study. The life cycle begins with a schizont surrounded by a unit membrane and containing a diplokaryon. The entire process of sporogony takes place in the host musculature. The sporogonic stages are enclosed in the pansporoblastic membrane. In each pansporoblast, sporogony gives rise to 8 sporoblasts; the octonucleate sporogonial plasmodium is lacking. In the course of schizogonic and sporogonic divisions, each kinetic center consists of 2 plaques, one located within and the other outside the nuclear envelope. The dividing sporonts and sporoblasts sevrets "metabolic" substances (granules, tubules) which are depostied in the pansporoblast. The uninucleate spore is long and cylindrical, measuring 19.1 X 2.4 micronm. A rectilinear manubrium traverses the spore. Its posterior end attenuates abruptly into a polar filament with 4 or 5 coils; its anterior end is attached to the polar cap, which is compressed by a double polar ring. The anterior part of the manubrium is surrounded by a polaroplast consisting of a "spongy" (vesicular) and a lamellar zone.


Some ultrastructural and functional aspects of the golgi àpparatus of Thelohania sp. (Microsporida) in the shrimp Pandalus jordani Rathbun.

Electron microscope observations on Thelohania sp. in the shrimp Pandalus jordani support the view that the Golgi complex in Microsporida is a "classical" one, composed of vesicular, vacuolar, and cisternal components. During development of the sporoblast, a portion of the Golgi complex is seen as an electron-dense reticulum enmeshing the core of the polar filament. Associated with the reticulum are electron-dense bodies. The reticulum and "dense bodies," reported in several previous publications, have not been well understood and have been given a variety of names. The evidence favors the view that these structures have secretory activity in which the reticulum concentrates or synthesized material, some of which takes the form of membrane-bounded granules. It is suggested that the most appropriate name for the reticulum is "reticulum golgien," and the the correct name for the "dense bodies" is the standard cytologic term, "secretion granules." The secretion granules apparently remain in the posterior part of the spore, and may be stored there for some as yet undetermined use.


Discotricha papillifera: structure and morphogenesis of a marine interstitial ciliate.

Discotricha papillifera Tuffrau, a marine interstitial ciliate, is redescribed with the aid of light, scanning, and transmission electron microscopy from cells collected at a New Hampshire beach. Presence of primitive membranelles as well as an advanced stomatogenesis is demonstrated. The ultrastructure, including a unique membrane-bounded septate structure, is described. The cell is tentatively placed in the nassulid suborder Microthoracina, but affinities with other groups are discussed.


Spontaneous malformations in squirrel monkey [Saimiri sciureus] fetuses with emphasis on cleft lip and palate.

Gross examination of a group of surviving and nonsurviving squirrel monkeys has revealed a high incidence of cleft lip and cleft primary palate defects with an associated anophthalmia. These defects, as well as single incidences of diaphragmatic aplasia, scoliosis, internal hydrocephalus, and funnel chest, are noted or described and discussed with reference to sex and parentage.


Observations on trichinosis in the rhesus monkey.

Monkeys infected with 2.0 larvae/g body weight died 31-41 days post-infection (PI): two of three monkeys infected with 1.0 larva/g body weight became moribund and were sacrificed at 50 days, but six of six monkeys infected with 1.0 larva/g body weight were healthy 225 days PI. Periorbital and facial edema and eosinophilia were observed in all groups during the second week PI, and myalgia and stiffening of joints was observed during the third week. High numbers of encyse, biceps brachii and deltoideus. Adult worms were recovered from the intestine 49 days PI. The morphological changes were essentially similar to those seen in humans and a generalized lymphoid hyperplasia was not observed. Thus, rhesus monkeys develop trichinosis which show similarities clinically, pathologically and morphologically to human disease.


A Müllerian duct remnant in an aged male talapoin monkey.

A pelvic mass in an aged, male talapoin monkey, believed to be of Müllerian duct origin, is described. Histologically, the mass was composed of smooth muscle cells and glandular epithelium, although the typical uterine organization of these tissues was not observed. The remainder of the genital system was that of a normal male primate.


Semi-free breeding of tropical Celebes macaques (Macaca tonkeana) in a continental European climate.

Celebes macaques have been successfully bred for four years in a free-ranging colony in French pre-Alps where they are exposed to continental European climate and temperature variation of 65 centigrades.


Intracellular uptake and alpha-amylase and lactate dehydrogenase releasing actions of the divalent cation ionophore A23187 in dissociated pancreatic acinar cells.

Intracellular uptake of A23187 and the increased release of amylase and lactate dehydrogenase (LDH) accompanying ionophore uptake was studied using dissociated acinar cells prepared from mouse pancreas. Easily detected changes in the fluorescence excitation spectrum of A23187 upon transfer of the ionophore from a Tris-buffered Ringer's to cell membranes were used to monitor A23187 uptake. Uptake was rapid in the absence of extracellular Ca2+ and Mg2+ (t1/2=1 min) and much slower in the presence of Ca2+ or Mg2+ (t1/2=20 min). Cell-associated ionophore was largely intracellular as indicated by fluorescence microscopy, lack of spectral sensitivity to changes in extracellular Ca2+ and Mg2+, and by equivalent interaction of ionophore with membranes of whole and sonicated cells. A23187 (10 micronm) increased amylase release 200% in the presence of extracellular Ca2+ and Mg2+. In the absence of Ca2+ (but in the presence of Mg2+) A23187 did not increase amylase release. A23187 (10 micronm) also produced Ca2+ -dependent cell damage, as judged by increased LDH release, increased permeability to trypan blue, and by disruption of cell morphology. The cell damaging and amylase releasing properties of A23187 were distinguished by their time course and dose-response relationship. A23187 (1 micronm) increased amylase release 140% without increasing LDH release or permeability to trypan blue.


Active phosphate transport across the urinary bladder of the toad, Bufo marinus.

Net transport of inorganic phosphate occurs in the absence of an electrochemical gradient from the mucosal to the serosal bathing solution in the isolated toad urinary bladder. This transport can be inhibited by metabolic inhibitors. The magnitude of this transport can be altered by changes in phosphate concentration or by the addition of parathyroid hormone.


Metabolic cost of sodium transport in toad urinary bladder.

The metabolic cost of active sodium transport was determined in toad bladder at different gradients of transepithelial potential. Deltapsi, by continuous and simultaneous measurements of CO2 production and of transepithelial electric current. Amiloride was used to block active sodium transport in order to assess the nontransport-linked, basal, production of CO2 and the passive permeability of the tissue. From these determinations active sodium transport, Jna, and suprabasal CO2 production, Jsb CO2, were calculated. Since large transients in Jna and Jsb CO2 frequently accompanied any abrupt change in deltapsi, steady state conditions were carefully defined. Some 20 to 40 min were required after a change in deltapsi before steady state of transport activity and of CO2 production were achieved. The metabolic cost of sodium transport proved to be the same whether the bladder expended energy moving sodium against a transepithelial electrical potential grandient of +50 mV or whether sodium was being pulled through "the active transport pathway" by an electrical gradient of -50 mV. In both cases the value of the ratio Jna/Jsb CO2 averaged some 20 sodium ions transported per molecule of CO2 produced. When the Na pump was blocked by 10(-2) M ouabain, the perturbations of the transepithelial electrical potential did not elicit changes of Jna nor, consequently of Jsb CO2. The independence of the ratio Jna/Jsb CO2 from deltapsi over the range+/-50 mV indicates a high degree of coupling between active sodium transport and metabolism.


An analysis of the binding of fluorescence probes in mitochondrial systems.

Measurements of the binding of the fluorescent probes 8-anilinonaphthalene-1-sulfonate (ANS) and ethidium ions to whole and disruped mitochondria and submitochondrial particles suggest that the inner mitochondrial membrane is freely permeable to the two probes. Equations relating the binding of permeant probes to the electro-chemical balance across the membrane of vesicular systems are derived and these equations used to analyze Scatchard plots of the binding of the two probes to energized and nonenergized mitochondria and EDTA particles.


Radioimmunoassay for myeloma idiotype.

Rabbit anti-idiotype antisera were prepared against four human myeloma proteins. These antisera demonstrated a capacity to bind the 125I-labeled autologous purified monoclonal IgG, but failed to demonstrate any binding to 125I-labeled normal IgG or to labeled myeloma IgG obtained from other myeloma patients. The anti-idiotypic antisera were used with 125I-labeled autologous myeloma IgG preparations and goat antirabbit IgG for specific radioimmunoassay with a sensitivity limit of 20 ng/ml. Little or no cross-reaction occurred between these anti-idiotypic antisera and normal IgG preparations or other myeloma IgG proteins.


Insulin and sodium bicarbonate treatment in diabetic ketoacidosis in children.

Nineteen patients, nine males and ten females had 24 episodes of diabetic ketoacidosis. Infection was the precipitating factor in the development of ketoacidosis. Recovery of ketoacidosis occurred with 0.7 units of crystalline insulin per kg of body weight. The insulin requirement is less than the generally recommended dose. Hypoglycemia, hypokalemia, and alkalosis were not developed in our children. Ketoacidosis was adequately corrected by 2.5 mEq of sodium bicarbonate per kg of body weight.


Effects of diphenylhydantoin and chloroquine on monkey liver microsomal mixed-function oxidases.

Sixteen adult male squirrel monkeys (Saimiri sciureus) were randomly divided into three treatment groups and one control group. Each treatment group received 10 mg/kg oral doses of diphenylhydantoin and/or chloroquine. Following sacrifice, in vitro assays for activity of liver microsomal mixed-function oxidases were run. The assays confirmed diphenylhydantoin as a potent inducer of mixed-function oxidases. Chloroquine administration had little affect on the enzymes assayed and did not inhibit the diphenylhydantoin induction.


Ocular accumulation and toxicity of certain systemically administered drugs.

Certain polycyclic compounds with a coplanar ring structure (phenothiazines, thioxanthenes, 4-aminoquinolines, and amitriptyline), monocyclic sympathomimetic amines, and other drugs become concentrated in the eyes of animals following acute or chronic systemic administration. Some are known to cross the placental barrier and accumulate in the fetal eye. Following drug withdrawal, these substances disappear relatively slowly from ocular tissues compared with other tissues. The main reason for the accumulation of these compounds seem to be their affinity for the melanin of the uveal tract and pigment epithelium and they therefore do not accumulate in the eyes of albino animals. The mechanism of uptake by melanin probably involves a "charge transfer" reaction involving the transfer of an electron from drug to melanin, which acts as an "electron trap" and in consequence binds the donor compound firmly. The accumulation of a nontoxic drug in the eye is not necessarily of clinical significance, but ocular damage can occur in patients on long-term tricyclic agents when the amount, duration, and frequency of dosage are sufficiently high. The most serious form of ocular damage is pigmentary retinopathy, which, if caused by chloroquine, is irreversible. In contrast, phenothiazine retinopathy is reversible. Lesions may also be produced in anterior structures of the eye, usually the cornea and lens, by both chloroquine and the phenothiazines, but they are of a relatively minor nature. Possible mechanisms for the oculotoxicity of the phenothiazines and antimalarials are discussed, particularly in relation to melanin.


Leishmaniasis in Brazil: XII. Observations on cross-immunity in monkeys and man infected with Leishmania mexicana mexicana, L. m. amazonensis, L. braziliensis braziliensis, L. b. guyanensis and L. b. panamensis.

Cross-immunity trials in monkeys (Cebus apella apella) and observations on experimental and natural infections in man confirm the separate identity of L. mexicana mexicana, L. m. amazonensis, L. b. braziliensis, L. b. guyanensis and L. b. panamensis. Neither L. m. mexicana nor L. m. amazonensis infections gave protection against subsequent challenge with parasites of the L. braziliensis complex; but recovery from infection with subspecies of L. braziliensis in most cases gave firm resistance to infection with the mexicana parasites. The failure of certain New World leishmanias to immunize against each other has an important bearing on taxonomy, future attempts to prepare vaccines against Leishmania, epidemiology and diagnosis.


Growth of an enveloped mycoplasmavirus and establishment of a carrier state.

The growth of an enveloped DNA-containing mycoplasmavirus (MVL2 obtained from R.N. Gourlay) has studied, by using the indicator host Acholeplasma laidlawii strain JA1. From virus one-step growth curves, artificial lysis experiments, and infected cell growth curves, it was found that virus infection is nonlytic. Newly infected cells grow slower and are osmotically more stable than uninfected cells. However, 4 to 6 h after infection, the cells reach a carrier state in which cell growth rate and osmotic fragility are indistinguishable from uninfected cells. Carrier cultures contain free virus. Every carrier culture cell gives rise to either a clone of carrier cells or a clone of MVL2-resistant cells.


Sarcocystis leporum in cottontail rabbits and its transmission to carnivores.

Muscle from Sarcocystis-infected cottontail rabbits (Sylvilagus floridanus) was fed to coccidia-free cats (Felis domestica) and dogs (Canis familiaris). Only cats became infected and shed sporocysts in their feces. The prepatent period ranged from 10 to 25 days and the patent period from 3 to 46 days. Sporocysts were fully sporulated when shed. They contained 4 sporozoites and a coarse granular residuum and averaged 9.4 by 13.6 micron (N=55). Doses of 200-75,000 sporocysts were orally administered to 5 domestic rabbits (Oryctolagus cuniculus). Domestic rabbits did not become infected, suggesting a strict host specificity for the intermediate host S. floridanus.


Transmission of Sarcocystis leporum from a cottontail rabbit to domestic cats.

Muscle tissue containing grossly visible cysts of Sarcocystis leporum from a cottontail rabbit (Sylvilagus floridanus) was fed to laboratory cats. Sporocysts averaging 13.2 x 9.7 micron were detected in the feces 14 days post-infection and were found until 69 days post-infection.


Blood parasites of some waterfowl from Victoria, Australia.

A total of 316 anatids (5 species) from Serendip Wildlife Research Station, Lara, Victoria, were examined for blood parasites. Twenty-two of the ducks (all five species) harbored Haemoproteus nettionis and one also harbored Plasmodium relictum. None of 12 dusky moorhens (Gallinula tenebrosa) were infected. There was no significant difference in the prevalence of H. nettionis between species or age groups of ducks. No evidence of infection with Leucocytozoon, Trypanosoma or microfilaria was obtained.


A species of Sarcocystis using owls as definitive hosts.

Sporulated oocysts found in the intestines of a Masked Owl (Tyto novaehollandiae) and a Barn Owl (T. alba) produced sarcocysts in mice. Schizonts were found in the livers of 3 mice that died at 7-8 days after dosing. Neither sarcocysts nor schizonts were found in chickens dosed with oocysts from a Masked Owl.


A comparative study of the anti-allergic effects of disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG).

A comparative study was carried out on the effects of a soluble derivative of baicalein, disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG) on the immediate type allergic reactions. BPS not only inhibited reaginic antibody-mediated reactions including antigen-induced mediator release from monkey lung, homologous PCA in rats, and reaginic antibody-mediated degranulation of mast cell, but also non-reaginic antibody-mediated reactions such as mediator release from guinea pig lung sensitized with ovalbumin and that from human lung caused by anti-IgE. The agent, however, did not affect the mediator release from lung of rats sensitized with dinitrophynylated ascaris extract plus Bordetella pertussis. On the other hand, DSCG showed characteristic properties as an inhibitor of reaginic antibody-mediated reaction. It is thus assumed that the functional site of reaginic antibody is well fixed with DSCG at a definite distance between the two-chromone-nuclei while that of IgG is readily fixed with the two molecules of baicalein or BPS.


A minirecord: an aid to continuity of care.

A simple, low cost computerized minirecord system (minimal essential record) has been in full operation for two years in the Medical Clinic of The Johns Hopkins Hospital. The primary objective of the minirecord system is to permit rapid retrieval of current information concerning Medical Clinic patients. The system provides a computer-printed listing of problems and medications in the front of each chart and on-line display of this information at strategically located computer terminals. The information is generated via existing simple systems with minimal additional effort and with the use of any terminology deemed appropriate. Chart review revealed that minirecords were actually present in 92% of the charts and that significant improvement occurred in the recognition of a subsequent visit of clearly defined problems and therapies noted on the initial minirecord. Current modifications will replace the separate minirecord and encounter form (registration and visit note) with a single form that will facilitate completion an updating. The rapid availability of this information provides a mechanism for coordinating continuing care in a university hospital system that is otherwise inevitably fragmented and composed of multiple health care providers.


Evaluation of indium-111 as a new high photon yield gamma-emitting "physiological" platelet label.

In order to evaluate indium-111 (111In) as a "physiological" platelet label, rabbit platelets were labeled in vitro with 111In-8-hydroxyquinoline. The in vivo behavior of 111In labeled platelets was then compared with that of chromium-51 51Cr) labeled platelets in the rabbit. Several important features were evident. First, unlike 51Cr, reasonable platelet labeling efficiency could be achieved with 111In, even when the platelets were suspended in small amounts of autologous plasma. Second, the initial recovery of platelets at 20 minutes after infusion was significantly higher for the 111In labeled platelets than for 51Cr labeled platelets, providing the platelets were suspended and "washed" in plasma. Third, the mean survival time of 111In labeled platelets, as estimated using four different mathematical models, was comparable with that of 51Cr platelets. Finally, the high photon yield of gamma emitting 111In, unlike 51Cr, permits quantitative gamma camera imaging of the in vivo distribution of labeled platelets. Thus, this nuclide possesses advantages as a platelet label that will foster statistically more accurate kinetic research as well as quantitative in vivo distribution studies in humans.


[Phospholipase A and lysophosphatidylcholine in the pathogenesis of "permeability cataracts" (author's transl)].

Phospholipase A and Lysophosphatidylcholine (LPC) have been shown harmful for normal lens permeability, inducing an efflux of intracellular macromolecules in organ cultures. These findings, superimposible to what has been shown in the lens for complement-dependent immune damage, along with the hypothesis that the cytotoxicity of complement is mediated by a phospholipase, are considered relevant as far as the pathogenesis of complicated cataracts in "immune" uveitis and the selfmaintenance of recurrent autoimmune (to lens proteins) anterior uveitis are concerned.


[Methods of evaluating the function of transplanted islets of Langerhans (author's transl)].

The various groups who are working on islet-transplantation used different parameters in determining the success or failure of their experiments. In our own transplantation-trials we tested the value of using the symptoms typical of diabetic humans for rats. These are: change in bodyweight, water intake, urine-volume and glucose content as well as the glucose-level in the blood. Special diabetic provocation-tests were also carried out with rats. It was shown, that the i.v. glucose-tolerance-test (IVGTT) and the glucose assimilation-coefficient (GAC) were able to demonstrate the reversal of the diabetic state after islet-transplantation. The tolbutamid-test gave no additional evidence about the success of the transplantation. Histological examinations should always be carried out in addition to the biochemical tests, because a decrease in the islet's-function is shown to depend on a higher rate of morphological regressions.


The fate of pedicle osteocutaneous grafts in mandibulo-facial restoration.

To overcome some of the problems encountered in the repair of extensive composite defects of the head and neck, several means of transfering bone and soft tissue--while preserving the blood supply by means of a pedicle--have been clinically attempted. The superiority of pedicle osteocutaneous grafts compared to free grafts is demonstrated in a series of experiments in monkeys and dogs. Conventional and tetracycline labelled histological specimens, from animals sacrificed at intervals from two weeks to six months after grafting, illustrate the dynamic changes in the grafts. Pedicle supported grafts appeared superior to free grafts and partivipated actively in bone reconstruction.


[Screening methods for the detection of alpha-1-antitrypsin deficiency in blood serum].

In order to spread in occupational medicine the simple screening test allowing to detect the alpha-1-antitrypsin deficiency, the conformability of four procedures with the method of radial immunodiffusion has been analysed. From the received data it results that for the preliminary diagnostics of deficiency in mass examinations methods based on separation of proteins on the agar gel, determination on the gelatinous membrane and the method of rocket immunodiffusion are suitable.


Lack of effect of thyroid hormones on the growth hormone response to thyrotropin-releasing hormone in acromegaly.

Serum growth hormone (GH) responses to thyrotropin-releasing hormone (TRH) were evaluated in 14 patients with acromegaly following treatment with thyroid hormones. After an initial TRH test, seven patients received L-triiodothyronine, 100 mug daily for seven days; the GH response to TRH was not significantly altered by this treatment. Similar findings were noted in two acromegalic subjects who were tested with TRH before and after longer periods of administration of L-thyroxine. Four of five additional subjects with acromegaly who had received replacement doses of thyroid hormones for an average of 6.6 yr demonstrated GH responses to TRH which were similar to those seen in subjects not receiving thyroid hormones. Acute or long-term administration of replacement doses of thyroid hormones seems to have minimal effect on the GH response to TRH in acromegaly.


Restriction and modification in Bacillus species: genetic transformation of bacteria with DNA from different species, part I.

Host specific restriction was detected in 13 Bacillus strains, when 63 strains of Bacillus subtilis and 15 other Bacillus strains were tested with phage phi 105C. These 13 strains were classified into 8 groups (M,H,C,N,E,F,G,P) by the type of restriction. M-type strains (B. subtilis Marburg 168, its derivatives, and two other strains) showed relatively weak restriction, restricting phi 105C from other groups of Bacillus by ratios of 10(-1) to 10(-3). Strains of groups H,C,N,E,F,G, and P restricted phi 105C from other groups by ratios of 10(-2) to 10(-8). It was confirmed with some of the strains that type-specific modification was endowed only by the last host. Furthermore, we isolated one restriction deficient mutant of B. subtilis Marburg 168-YS11, which had also lost its modification phenotype.


[The effect of metabolic control on the development of late complications of diabetes (author's transl)].

The fate of the diabetic today is essentially determined by the late complications of diabetes. Of the forms of clinical expression of diabetic microangiopathy, nephropathy and retinopathy are the most significant. Findings are presented which suggest that diabetic microangiopathy is not of genetic or immunologic origin, but is to be considered a consequence of insulin deficiency. More recently, some studies have been carried out which which strongly support the concept that metabolic control of the diabetic prevents or at least delays the development of late complications of diabetes. For this reason an optimal for control of diabetes, if at all possible with aglycosuria, should be aimed at.


[Morphology of diabetic nephropathy (author's transl)].

Renal complications occur frequently in diabetics. Glomerular lesions exist in basal membrane thickening, diffuse and nodular glomerulosclerosis, exudative lesions and glomerular aneurysms. Tubular and interstitial changes are characterized by Armanni-Ebstein cells, by pyelonephritis and papillary necroses. Vascular changes occur in the form of arteriosclerosis and arteriolosclerosis. Nodular glomerulosclerosis is characteristic of diabetic renal damage, all other changes only occur more frequently in diabetics. Recently, studies deserve attention which suggest a regression of glomerular lesions if the diabetic metabolism is normalized.


[Clinical aspects of diabetic nephroangiopathy (author's transl)].

Diabetic nephropathy is a dangerous and insidious complication of diabetes mellitus. The course is variable and from the statistical point of view usually unfavorable. The pathogenesis of the complaint is not fully known. Of the numerous hypotheses, the one most favored is a defective glucose metabolism with uncontrolled inundation of the kidney cells with glucose. The predominant symptom is proteinuria. Early recognition and optimal correction of the metabolic disorder may possibly delay the manifestation of diabetic nephropathy for a time. The use of Somatostatin is attracting great attention today. With such a preparation, the stabilization of diabetes could be facilitated.


[Dietetic therapy of diabetes and renal insufficiency (author's transl)].

Coincidence of chronic renal failure and diabetes mellitus brings with it serious therapeutic problems, especially in dietetic treatment. It is not possible to wish to do justice to all the therapeutic principles of the text books to the same extent. The condition of renal failure with its demands takes precedence in all cases. But if the renal disease has not yet led to a perceptible retention of normal urinary constituents in the serum, no specific dietary measures are necessary. In these cases, the diabetic diet is proceded with in the usual manner.


[Dialysis treatment of advanced diabetic nephropathy (author's transl)].

Dialysis treatment of patients with diabetic nephropathy turns out to be difficult because of numerous late complications which arise in addition to the renal disease and which often influence the direction of the course of the disease. But this experience does not in the least justify the exclusion generally of patients with diabetic nephropathy from dialysis the-rapy. Hemodialysis and peritoneal dialysis are equally suitable for  the treatment of renal insufficiency; patients with accumulated hemorrhagic complications (e. g. vitreous hemorrhages) should be treated by peritoneal dialysis for preference, and those with a predominant hypertension by hemodialysis. Early preparation for dialysis treatment is of great importance.


[Future prospect of diabetes therapy (author's transl)].

The treatment of diabetes may be improved by a more physiological insulin supply and by supplements to the insulin supply. Grafting the entire pancreas or transplantation of the islet cells represents an improvement in the insulin supply. But because fo the lack of donor material and immunological difficulties, the realization of these two methods may be questionable. On the other hand the implantation of an artificial B cell seeems realizable in the foreseeable future. Such a method would be indicated in a diabetic whose life is threatened by late complications. Somatostatin is available as a supplement to insulin therapy because it eliminates the growth hormone as possible source of diabetic vascular complications and it blocks the secretion of hormones with a contrainsular effect.


[New aspects of clinical hepatology (author's transl)].

Studies of the enzymes participating in the urea cycle and urine synthesis in the liver punctate show that typical changes occur in the enzyme pattern during chronic liver diseases which yield new starting points for the diagnostic classification and prognostic assessment. From studies on the metabolism of the bile acids it appears that, among the conditions for cholestasis, a fetal snythetic pathway for the bile acids with primary side chain oxidation of the cholesterol is followed, and intrahepatic monohydroxy-bile acids are formed. The pathogenetic significance of these bile acids for cholestasis is discussed.


[Effect of arginine ketoglutarate on the detoxifying capacity of the liver in cirrhosis of the liver (author's transl)].

According to the present studies it is shown that arginine ketoglutarate in sufficiently high dosage (3x3 g daily by mouth) produces a significant lowering of plasma ammonia and free serum phenols with a high-protein diet in patients with liver cirrhosis, compared to a previous day without this substance. The ammonia reduction can be explained by a significant increase in urea synthesis, measured by the urea nitrogen content of the 24-hour urine. The simultaneous lowering of pathologically raised serum levels of free phenols can be explained by an improved oxidative decomposition of these substances. No stimulation of insulin secretion worthy of note occurred after oral administration of 9 g arginine ketoglutarate.


[Comparison of duck embryo vaccine and Hempt's vaccine for rabies vaccination (author's transl)].

For many years, Hempt's vaccine has been used in Germany for vaccination against rabies. In recent years the duck embryo vaccine has been gradually introduced in its place. From 1970 to 1975, 658 consultations were undertaken at the Hospital of the Tropical Institute at Hamburg because of the risk of rabies. 267 persons had to undergo vaccination, 159 of them being treated with Hempt's vaccine and 108 with duck embryo vaccine. Side effects of a more severe type were not seen in either group. Disadvantages of the duck embryo vaccine are that more individual inoculations are necessary, significantly more frequent and more persistent local and general vaccination reactions occur and that there is a delayed, possibly weaker formation of antibodies.


[Muscular insufficiency as a partial cause of osteoporosis. Significance for therapy (author's transl)].

Osteoporosis as a disease is more than a mere development of porosity of the bone. Between the axial skeleton and the musculature of the trunk there are mutaual relationships affecting circulation, metabolism and function which become active in the genesis and development of an osteoporosis. For this reason, therapy must not only be directed towards reossification of the bony skeleton, but also to the elimination of muscular insufficiency and improvement of the functional capacity of the musculature of the trunk.


Dicentric yields induced by gamma-radiation and chromosome arm number in primates.

To evaluate the effect of the chromosome arm number on the yield of dicentric chromosomes, frequencies of gamma-ray-induced chromosome aberrations were examined with peripheral lymphocytes from three different primate species, Saimiri sciureus (arm number, 77), Macaca fascicularis (arm number, 83) and Nycticebus coucang (arm number, 99). Irradiated blood samples were cultured by the same standard technique as that commonly used for human lymphocytes. The yields of dicentrics and dicentrics plus rings at doses of 100, 200 and 300 rad of gamma-irradiation were not significantly different among the three species, in spite of the difference in the chromosome arm number. Furthermore, dose-response relationships for these species were consistent with that for man. Statistical analysis indicated that the expected dicentric yields calculated from the arm number model were significantly different from the observed yields at 200 and 300 rad doses (P less than 0.01). From these results it can be pointed out that there is no correlation between the yield of dicentrics and the effective chromosome arm number, and that the chromosomal radiosensitivity of these primates is essentially the same as that of man, at least in the lymphocyte system.


Effects of treating drosophila females with TEM on their mortality, and the yields of mutation recovered from x-irradiated sperm.

Ring-X-bearing Drosophila males were irradiated with 0, 1000, 2000 or 3000 R of X-rays and mated to females that had been injected with saline or 10(-4) M TEM. The mortality and the fertility of the treated females were recorded. The rate of dominant lethals, of entire sex chromosome loss and partial loss of the Y chromosome, the sex ratio, and the rate of mosaics were determined on the progency. TEM slightly increased the rate of mortality of the females. But it did not influence the yield of mutations recovered from the irradiated spermatozoa.


Isolation and characterization of chlorate-resistant mutants of the blue-green alga Nosoc muscorum.

Spontaneous chlorate-resistant (Clr) mutants of three classes were isolated from Nostoc muscorum under three different selective conditions. A Clr-N2 class of mutants lacked nitrate reductase and showed nitrate inhibition of nitrogen fixation. A Clr-NO3 group of het+ nif- mutants formed heterocysts, but lacked nitrogen fixation and active nitrogenase enzyme. The Clr-NO2 class included those mutants deficient in both active nitrogenase and nitrate reductase, as they were unable to grow at the expense of molecular nitrogen or with nitrate nitrogen. The results suggest a common genetic determinant of active nitrogenase and nitrate reductase in the blue-green alga N. muscorum.


Clinical immunity in acute gastroenteritis caused by Norwalk agent.

To examine immunity in viral gastroenteritis, we challenged and then rechallenged 12 volunteers with Norwalk agent and evaluated symptoms, jejunal biopsies and serum antibody. With the first challenge, gastroenteritis developed in six volunteers but not in the others. When rechallenged 27 to 42 months later, the six who became ill initially again had gastroenteritis with jejunal lesions; in the six previously immune volunteers illness or jejunal lesions did not develop. Four of five ill volunteers had increases in serum antibody to Norwalk agent after both challenges. Serum antibody did not increase in three immune volunteers after either challenge. Four volunteers who had twice become ill underwent a third challenge four to eight weeks after their second illness. In one gastroenteritis developed; in three, it did not. These findings indicate two forms of immunity for viral gastroenteritis, one of short and the other of long duration. Factors other than serum antibody appear important in immunity to Norwalk gastroenteritis.


The epidemiology of drug abuse: current issues. Ecological studies of narcotic addiction.

Narcotic addiction is concentrated in certain places and among particular social groups. Heretofore it has not been possible to assess which environmental factors are critical for the initiation of narcotic use, its transition to narcotic addiction; and subsequently, entry into treatment or whether there are environments which select those particularly prone to social deviancy while others migrate out.  There are few systematic descriptions of the social and environmental distribution of narcotic addicts.  This paper describes the initial results of assessing the characteristics of the social environment (1970 Federal Census) of 3,000 individual narcotic addicts from the Lower East Side of Manhattan who were treated at the Beth Israel Medical Center. Pearson correlations between treated addiction ratios and 1970 Census characteristics were calculated for 13 health areas. Out of 103 socio-economic characteristics from the NIMH Mental Health Demographic Profile System, 29 were statistically significant at p less that 0.01 and 28 at 0.01 less than p less than 0.05. Highly significant correlations were found for households with children, female headed (r = .94, F= 90.3) and population in poverty (r = .89, F = 41.7). Correlations with density (over 1.01 persons per room) or population mobility (residing in different house five years ago) were not statistically significant. This paper has outlined some of the methodological and theoretical problems of ecological studies of narcotic addiction, and emphasized the need for concentration on the socio-dynamics of diffusion. Methodological problems include consideration of the time and place of onset; demographic standardization; ascertainment differentials; clinical characterization; and assessment within individuals of ecological correlations.


Computed tomography or orbital lesions. A cooperative study of 210 cases.

Computed tomography (CT) has given us a new method for examining the orbit and its contents. The technique of examination is described, and the indications for the application of computed tomography in ophthalmology are considered: suspected orbital tumors, unilateral exophthalmos, pareses of the ocular muscles, traumatic lesions and malformations in the region of the orbit. The findings in 210 cases of orbital lesions examined in this study are reported and the differential diagnosis is discussed. Considerable improvement and greater accuracy in diagnosis have been achieved in the field of ophthalmology by using computed tomography. Early tumor visualization is possible without risk or discomfort to the patient.


Carbamazepine--a double-blind comparison with phenytoin.

In a double-blind crossover study, carbamazepine and phenytoin were compared as single anticonvulsants in 47 patients with focal and major generalized seizures. Each drug provided superior seizure control in about half the patients, but significantly fewer patients had objective side effects while taking carbamazepine. Neuropsychologic testing showed improved performance in cognitive function and emotional status of patients while and carbamazepine. No hematotoxic complications arose, but vigilant follow-up is advised. Mean serum level of carbamazepine was 9.3 microng per milliliter with a suggested therapeutic range of 8 to 12 microng per milliliter reached by eventual doses of 16 to 20 mg per kilogram. Carbamazepine offers an independent choice of improved seizure control with a possibility of fewer side effects.


Sensations of ocular movement in seizures originating in occipital lobe.

Two patients with structural lesions had illusions of eye movement as the earliest manifestation of their seizures. One patient had a right occipitoparietal arteriovenous malformation and the other had a tentorial meningioma encroaching on the left occipital lobe. Symptoms were controlled by anticonvulsants and subsequent surgery in both cases. The characteristic feature of this rare form of seizure onset is a unilateral sensation of eye movement in the absence of oscillopsia.


[Juxta-ampullar duodenal diverticula and bilio-pancreatic pathology. Considerations on 2 clinical cases].

75% of duodenal diverticula occur in the second or descending portion where, in 60% of cases, a juxta-Oddian site is involved. In about 10% of cases, juxta-Oddian forms may be responsible for symptoms due to their own effects or those induced in the biliary and pancreatic area. Two cases in female patients are presented and the subject is examined from all aspects in the light of 85 cases from the literature. Exact preoperative diagnosis is difficult. Radiological examination of the digestive tract and bile ducts, though by no means conclusive, is the only effective instrumental aid. When the symptoms are clear or indicative, surgery is necessary to prevent complications. In the two reported cases, an unevenful course and complete recovery were observed after diverticulectomy combined with papillosphincteroplasty.


Anti-microbial treatment for hospital carpets.

Seven commercial bactericides, three hospital disinfectants and one carpet finish were examined for their ability to show diffusible bactericidal activity in agar, their ability to prevent the multiplication of a known number of micro-organisms applied to the treated carpet and the occurrence or otherwise of odours after contamination of the carpet samples with food and secretions. None of the carpet bactericides tested showed any diffusible bactericidal activity, but some had a certain degree of effectiveness in suppressing odours.


Ureteral injury following irradiation therapy for carcinoma of the cervix.

Ureters tolerate radiation well as manifested by the low incidence of injury. However, ureteral injury can occur with high-dose radiation especially when the majority is delivered by radium. Eight such cases are presented. A retrospective study of 100 asymptomatic women treated with radiation for cervical carcinoma over 5 years previously demonstrated only 4 incidences of ureteral injury if dilatation was used as the indicator. To the contrary, 5 patients had improvement of their pre-treatment intravenous pyelogram following radiation. Emphasis was placed on closer followup of the ureters by intravenous pyelograms after high-dose radiation.


Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.


Detection of orbital and intraocular foreign bodies by computerized tomography.

Localization of intraocular and orbital foreign bodies with computerized tomography (CT) was evaluated in eight patients and an experimental model. CT examination was particularly helpful in cases with multiple similar foreign bodies and in identifying foreign bodies too radiolucent to be seen by standard skull x-rays. Limitations of CT technique included insufficient resolution to localize a foreign body immediately adjacent to the sclera as either intraocular or extraocular, and obscuration of a small foreign body by artifacts from an adjacent, larger foreign body.


Percutaneous absorption of testosterone in the newborn rhesus monkey: comparison to the adult.

Percutaneous absorption of testosterone was determined in newborn rhesus monkeys, an animal model which is relevant to man. Mean percentage of absorptions of 4 and 40 microng/cm2 in the newborn were, respectively, 22.5 +/- 2.2 (SD) and 6.8 +/- 2.1. Statistical comparisons (Student's t-test) of these results with those obtained with adults show no significant difference (P greater than 0.05) in skin penetration of testosternoe in newborn and adult rhesus monkeys. In the newborn, the efficiency of absorption (percentage) decreased when the topical dose was increased 10-fold. However, the total compound absorbed per cm2 area of skin actually increased from 0.9 to 2.7 microng. With one other newborn rhesus, a topical dose of 40 microng/cm2 was applied to the ventral forearm and the area was occluded for 24 hr. Percutaneous absorption was 14.7%, a value twice that from nonoccluded absorption. Systemic absorption from a topical dose becomes critical in the newborn because the ratio of surface area (cm2) to body weight (kilograms) in the newborn is 3 times that in the adult. Given equal application area of skin per newborn and adult, the systemic absorption in the newborn becomes 3 times that of the adult when based on kilograms body weight. With a different ratio of skin surfact to body weight, the therapeutic ratio probably is lower in the newborn than in the adult when the compound is applied topically.


[Myxosporidia of the cartilaginous fish of the Patagonian shelf (shore of Argentina)].

5 species of myxosporidians of the genus Chloromyxum were found in the gall bladder of Chondrostei from the Pathagonian shelf (Argentina coast). 4 species of them are new ones. This indicates that the species Chloromyxum leydigi mentioned for all Chondrostei is a collective species which needs a revision. Caudal filaments and ribs of the valves of spores of myxosporidians are more developed in species parasitic in fishes getting food from water mass and predators and to a lesser extent in species getting food from the bottom.


[Apiosome organization and their systematic position].

The ability of apiosomes for the formation of non-contractile stems (such as epistylids) and colonies suggests to refer them to the family Epistylidae rather than to Scyphididae. On the other hand, the atrophy of the stem in the majority of the species, changes in the structure of the foot, in the form and position of the nuclei under the effect of parasitism on fishes suggest their separation into a distinct subfamily, Apiosomatinae subfam. n.


[Medullary aplasia after acute colchicine poisoning. 20 cases].

Out of 84 patients with colchicine poisoning hospitalised between 1966 and 1976, 11 died during the first 72 hours. Amongst the 73 survivors, 20 showed signs of marrow aplasia between the 3rd and 6th days, lasting on average 4 days. The average amount of colchicine ingested by these patients was 0.5 to 0.8mg/5g. Marrow aplasia was associated with: -- infectious episodes in all cases, -- haemorrhage in 50%, -- dilution hyponatraemia in 25% (but in 50 % of patients if those in renal failure are excluded), -- regressive polyneuropathy in 10 % of cases, -- secondary alopoecia in all cases, -- weight loss of more than 10 % of initial weight in 60 %. Two patients died as a result of septicaemia. This mortality rate of 10 per cent despite the brief duration of the aplasia and the absence of underlying haematological disease would appear to be related to the susceptibility of these poisoned patients to endogenous secondary infections, essentially intestinal in origin.


Hypocalcemia in bulls after EDTA infusion; variations among individuals.

EDTA infusion on bulls is well suited to induce hypocalcemia. There exist individual differences in the bull's reaction to EDTA, and the bulls' degree of response is reduced by age. The response also differs from bull to bull when they are tested at different points in time. Health card recording conducted in Norway gives the possibility of estimating the heritability for various diseases. The reaction  of the bulls to biological tests may also be compared to the daughters' resistance to various diseases. These experiments are conducted in the hope of finding some correlation between the bull's reactions on EDTA infusion and their daughters; resistance to paresis puerperalis.


The interactions of the separated strands of satellite DNAs with other DNAs: 1. Conditions for associations of the alpha-satellite of the guinea pig with heterologous double-stranded DNAs.

The separated H- and L-strands of the alpha-satellite of the guinea pig, Cavea porcellus, recovered from centrifugation in alkaline CsC1 gradients, from complexes with 7 different double-stranded (ds) DNAs including those of 1 bacteriophage, 2 prokaryotes, 2 invertebrates and 2 mammals. The complexes are not artifacts due to in vitro labeling of the satellite, methods of collection, the presence of divalent cations, or the fact that trace amounts of single-stranded (ss) DNAs are used. More complex dsDNAs, such as that recovered from nicked RF M13, do not associate with dsDNAs.


RNA polymerase from Bacillus subtilis: isolation of core and holo enzyme by DNA-cellulose chromatography.

A new procedure for the purification of B. subtilis RNA polymerase, based on mild lysis of cells, low speed centrifugation, gel filtration, DEAE-Sephadex chromatography and affinity chromatography on DNA-cellulose, yields three forms of enzyme referred here as enzyme A, B and C. As revealed by SDS gel electrophoresis, enzyme A has the subunit structure of core polymerase plus some small polypeptides. Its catalytic properties are similar to those of core polymerase. Enzyme B has the composition of core polymerase. Both enzymes A and B can be stimulated by the addition of beta factor. Enzyme C has the holo-enzyme composition. The pattern of sensitivity of the three forms of enzyme towards KCl are very different: enzymes A and B, even at low concentration of salt, are inhibited with all the DNA templates tested, whereas enzyme C shows a pattern of stimulation specific for each DNA tested. The transcripts of the three enzymes on phage SPP1 DNA template have been analyzed by hybridization to the separated strands. Only enzyme C selectively transcribed the H strands.


Sequence analysis of the 3' non-coding region of mouse immunoglobulin light chain messenger RNA.

Using an oligonucleotide d(pT10-C-A) as primer, cDNA has been transcribed from the 3' non-coding region of mouse immunoglobulin light chain mRNA and sequenced by a modification1 of the 'plus-minus' gel method2. The sequence obtained has partially corrected and extended a previously obtained sequence3. The new data contains an unusual sequence in which a trinucleotide is repeated seven times.


X-ray absorption studies of halide binding to carbonic anhydrase.

X-ray absorption measurements of bovine carbonic anhydrase B have been made at the the Stanford Synchrotron Radiation Project with a spectrometer operating in the fluorescence mode. Differences in absorption at and beyond the zinc K-edge near 9664 ev have been observed upon the addition of bromide or iodide. The additional absorption in k space, out to k approximately 7 A-1, obtained upon the addition of iodide has been compared with the absorption in this region of a ZnI2 sample. The similarities between these absorptions lead to the conclusion that the zinc-iodide distance in the protein is 2.65 +/-0.06 A; it is known to be 2.62 A in ZnI2. This shows that the iodide binds directly to the zinc in the protein.


Rapid transmembrane movement of newly synthesized phospholipids during membrane assembly.

The transbilayer distribution of phospholipids in Bacillus megaterium is asymmetrical, with twice as much phosphatidylethanolamine internally as externally (Rothaman, J. E. & Kennedy, E. P. (1977) J. Mol. Biol. 110,603-618). We now report that the biosynthesis of phosphatidylethanolamine is also asymmetrical. Newly synthesized phosphatidylethanolamine was found first on the cytoplasmic side of the membrane of pulse-labeled cells and later was redistributed until the specific radioactivity of the outer face became equal to that of the inner face of the bilayer. The rate of transmembrane movement is at least 30,000 times faster than the rate of spontaneous diffusion (flip-flop) of phosphatidylethanolamine across artificial phospholipid bilayers, indicating that transmembrane movement must be a facilitated process in living cells, perhaps involving membrane proteins.


Radioimmunoassay of a human serum growth factor for Balb/c-3T3 cells: derivation from platelets.

A radioimmunoassay has been developed for the detection and quantification of a human serum polypeptide that has growth-promoting activity for confluent Balb/c-3T3 cells. Antiserum to this growth factor does not recognize antigens in mouse, guinea pig, or bovine serum but does detect some crossreacting antigen in the serum of the New World monkey Cebus albifrons and more in the serum of the Old World rhesus monkeys Macaca mulatta and M. fascicularis, demonstrating that the antigenic determinants of the growth factor have a degree of species specificity. Serum derived from whole human blood contains approximately 770 pg of the growth factor per mg of protein; serum derived from platelet-poor blood contains about 112 pg of the growth factor per mg of protein. As much as 1 microng of the growth factor per mg of protein has been recovered from human platelets by heating them at 100 degrees for 2 min. Approximately 1-2 ng of the growth factor, in either whole serum or platelets, stimulates 5 to 10 X 10(3) confluent Balb/c-3T3 cells to replicate. The heat treatment of platelets allows the purification and quantitative recovery of the growth factor from blood.


Interaction of different egg parts in determination of various body regions in Drosophila melanogaster.

When Drosophila melanogaster embryos were ligated at very early stages of nuclear multiplication (45-60 min after egg deposition) for the entire period of embryogenesis, egg fragments of variable sizes were able to continue development up to the hatching stage. These ligated embryos differentiated larval structures; anterior fragments formed larval head and posterior fragments formed larval abdominal structures. Ligation always prevented the differentiation of some of the intermediate larval bands whereas the terminal ones were always formed. Identical results were obtained when embryos (45-60 min after egg deposition) were temporarily ligated for only 5 min. However, puncturing with a fine glass needle immediately after temporary ligation through the ligated area could give rise to complete differentiation of all the bands. Since puncturing disrupted the barrier produced by ligation, we propose that interaction between anterior and posterior egg regions is necessary to allow complete development.


Localization of RNA polymerase in polytene chromosomes of Drosophila melanogaster.

RNA polymerase (RNA nucleotidyltransferase) B (or II) and histone H1 of Drosophila melanogster were localized on salivary gland polytene chromosomes using the indirect immunofluorescence technique. RNA polymerase B is present almost exclusively in puffs and interband regions, whereas histone H1 is found primarily in bands. The puff at region 3C, known to be transcriptionally active in larval salivary glands, gives a bright fluorescence with antibodies against RNA polymerase B. This fluorescence disappears after exposure of the larvae to 37 degrees for 45 min. The heat shock treatment results in a general reduction of fluorescence intensity with the appearance of brightly staining heat shock puffs. Heat-induced removal of RNA polymerase molecules from a puff does not immediately alter its morphology. We propose than an interband represents that fraction of the total number of gene copies in a band that are active, the inactive copies being present in a condensed form in the adjacent band. Large puffs would originate through the decondensation and activation of most or all gene copies in a band.


Structure-function relations in phosphorylcholine-binding mouse myeloma proteins.

The binding site interactions between the phosphorylcholine (phosphocholine)-binding mouse myeloma proteins TEPC 15, W3207, McPC 603, MOPC 167, and MOPC 511 and the isotopically substituted hapten phosphoryl[methyl-13C]choline have been investigated using 13C and 31P nuclear magnetic resonance (NMR) spectroscopy. Each protein exhibits a unique NMR pattern, but extensive similarities in chemical shift parameters upon binding of hapten to immunoglobulin suggest a significant degree of conservation of important hapten-binding site interactions. Moreover, independent binding studies, in conjunction with the NMR data, allow construction of a simple model of the binding sites of these antibodies, analyzed in terms of the relative strength of interaction between hapten and two main subsites. The NMR evidence supports the view that the heavy chains of these proteins dominate in interacting with bound phosphorylcholine; the various subspecificities of these proteins for phosphorylcholine analogues can be accounted for by amino acid changes in the hypervariable regions of the heavy chains.