The lack of deep reflexes in myotonic dystrophy. Clinical and electrophysiological observations have been carried out on 12 patients with myotonic dystrophy. Neurological examination showed that the tendon reflexes were absent or weak in almost all cases, whereas the cutaneous reflexes were normal. Examination of both deep and superficial sensibility gave normal results. Electromyography confirmed widespread "myopathic" activity and myotonic discharges were recorded on insertion of the needle electrode and at rest. Motor and sensory conduction velocity in the ulnar nerve and motor conduction in the peroneal nerve proved to be normal. Repetitive supramaximal nerve stimulation showed in 10 cases a decrease in potential amplitude, more evident at higher frequencies of stimulation. In the 2 other cases, by contrast, an increase in amplitude was observed, and this was suggestive of a partial presynaptic block. The jaw reflex was absent in 5 cases and reduced in amplitude in the 7 other cases. The results of blink reflex investigations were normal, with the exception of 2 cases where no early response was elicited. Spinal monosynaptic reflexes were absent in 7 cases after both electrical (H reflex) and mechanical stimulation (T reflex), whereas the response to direct stimulation of nerve motor fibres (the M response) was always present, even though reduced in amplitude. Such data lead one to reject the hypothesis that the absence of deep reflexes is due to pathological change in the muscle spindles. It seems more likely that the selective atrophy of Type 1 muscle fibres, known to be involved in deep reflex responses, is responsible for the early disappearance of the tendon reflexes.


Cell-mediated immunity to human myelin basic protein in schizophrenic patients. Cell-mediated immune response to myelin human basic protein was studied by the macrophage migration inhibition test in patients suffering from schizophrenia. Eighteen out of 32 patients with chronic schizophrenia demonstrated human basic protein-induced inhibition of the migration index, while 4 out of 41 acute schizophrenics showed an inhibition of macrophage migration.


International collaborative study of the spinal muscular atrophies. Part 2. Analysis of genetic data. Most of the cases in the present study are of the juvenile onset, proximal form of spinal muscular atrophy. The results of the study indicate that the majority of these cases are due to one or more autosomal recessive genes, with very few being inherited as a dominant trait. Affected individuals very widely in the severity of the disease. When 2 or more sibs are affected, they tend to be similar as regards severity, but there are a substantial number of sibships in which this is not so. The data are consistent with either a single gene, with a wide range of expressivity due to the effects of other genes and/or environmental influences, or 2 or more genes, but with considerable overlap in their expression.


Cerebrovasculature permeability changes following experimental cerebral angiography. A light- and electron-microscopic study. Morphological alterations of the cerebral vasculature as related to the permeability of plasma proteins and angiographic contrast media following unilateral cerebral angiography were studied. Both Evans blue albumin and horseradish peroxidase were employed as protein tracers for light and electron microscopy investigation respectively. Grey matter regions of the cerebral cortex, cerebellum corpus striatum, hippocampus and midbrain showed the most extensive and consistent leakage of these protein tracers. The most extensive penetration of EBA was noted at 1 hr following cerebral angiography as compared to the 5 or 30 min sample times. Permeability changes were noted in small venules and arterioles as well as capillaries. The extent of permeability, however, was appreciably greater in the capillaires as evidences by rapid extravasation of HRP into the surrounding neuropil extracellular spaces. The glial basement membrane surrounding the perivascular spaces of small venules and arterioles precluded rapid penetration of HRP into the neuropil interstitium. Opening of the tight junctions between the endothelial cells was primarily responsible for the extravasation of HRP in all vessel types. Furthermore, it is out opinion that the hyperosmolar nature of the contrast medium is responsible for opening of these tight junctions.


Spinal muscle in scoliosis. Comparison of normal and scoliotic rabbits. Spinal muscle biopsies from 7 rabbits with experimentally-produced scoliosis and from 4 normal control rabbits, were examined histologically and histochemically. One scoliotic rabbit showed selective Type 2 fibre atrophy in its muscles, but in general there was no difference between the normal and the scoliotic rabbits. The percentage area of muscle occupied by Type 1 and Type 2 fibres was determined using a computer controlled microscope. There was no asymmetry in the muscles of either the normal or the scoliotic rabbits on the two sides of the spine. These results suggest that the abnormalities and asymmetry of fibre type proportions reported in human scoliotic muscles are not a consequence of the scoliosis. Within the limits of the study, it is suggested that the abnormalities reported in the muscles of human scoliotic patients are at least an important factor in the causation of "idiopathic" scoliosis.


Penetration of protein tracers into the epiretinal portion of the optic nerve in the rabbit nerve. Horseradish peroxidase and fluorescein-labelled globulin were injected into the vitreous of adult and 11- to 13-day-old New Zealand albino rabbits. Both tracers diffused rapidly into the myelinated nerve fibre layer (the "medullary rays"), which extends over a long distance within the retina in these animals. The tracers penetrated also for some distance into the optic nerve beyond the lamina cribosa, where they were incorporated into a large number of cells in the nerve. This finding of a rapid diffusion of macromolecules into the medullary rays after intravitreal injection makes this experimental model suitable for the study of factors interfering with myelin or myelination.


HLA antigen frequencies in paralytic dementia. HLA typing was performed on 75 caucasian and 58 black patients with paralytic dementia hospitalized at 2 state mental institutions in New York. Serological testing was performed to confirm previous infection with T. pallidum. The caucasian patients showed an increase in B18(18.7% vs. 9.6% in controls). The black patients showed an increase in A2 (48.3% vs. 28.7% in controls) and an increase in B7 (27.6% vs. 15.7% in controls.


The ultrastructure of the sheath around chronically implanted electrodes in brain. Insulated, bipolar stainless steel electrodes were chronically implanted in various regions of the cat brain and the long-term structural changes in the tissue surrounding the electrodes were studied by light and electron microscopy. A sheath surrounded and separated the electrode from normal grey or white matter. A layer of foreign body giant cells of variable thickness was formed adjacent to the electrode. This layer was attenuated in some places so that it was unrecognizable by light microscopy. The bulk of the sheath structure consisted of collagen fibrils, leptomeningeal cells and hypertrophied astrocytes. Areas consisting of modified leptomeningeal cells with long thin processes we designated as spongy areas. These have not been previously reported using the electron microscope. Glycogen bodies were seen in leptomeningeal cells. Astrocytes became greatly enlarged and were more numerous in and around the sheath. Oligodendrocytes contained lamellar bodies, and direct continuity was shown between a lamellar body and an adjacent myelin sheath. Myelin was seen in abnormal sites (around oligodendrocytes and neurons) and in unusual configurations. Neuronal changes near the sheath included whorls and stacks of modified endoplasmic reticulum and the presence of cytoplasmic nucleolus-like bodies. Reactive, regenerative and degenerative axons were observed. Blood vessels were more numerous in the sheath and surrounding tissue than normal. Perivascular spaces were prominent even around capillaries and often plasma cells and monocytes were in these spaces. As compared to normal tissue the extracellular space is noticeably increased. Electrodes passing through ventricles were surrounded with a sheath covered with ependymal cells. This sheath was comparable in structure to the sheath present around the electrode in other locations.


Electron microscopic observations of the mesencephalic nucleus of the fifth nerve in the Selachian brain. The mesencephalic nucleus of the trigeminal nerve (mes V) in the brain of the skate (Raja oscellata) was studied by electron microscopy. Mes V neurons are large (40-80 mum diameter) and are located in the periventricular grey matter. Their perikaryal cytoplasm is rich in Golgi apparatus, small mitochondria, rough endoplasmic reticulum, polysomes and bundles of neurofilaments. A striking feature is the presence of masses of glycogen granules, at times surrounded by membrane wrappings and lysosomal bodies. Two types of conventional synaptic contacts were made onto mes V perikarya and dendrites. One had round, agranular vesicles and usually also contained dense-cored vesicles, the other had flattened, pleomorphic, agranular vesicles and usually lacked dense-cored vesicles. Additional membrane complexes consisting of a region of gap junction flanked by sites of desmosomal attachment were observed to link neighbouring mes V neurons. Somato-somatic, dendro-somatic, axo-somatic, and dendro-dendritic junctions were noted. Except for the somato-somatic union, one or more chemical synapses were located close to the sites of gap junctions.


Prenatal development of Bergmann glial fibres in rodent cerebellum. The external granular and molecular layers in the foetal cerebellar cortex of mice and rats were examined by electron microscopy for the presence of Bergmann glial fibres. Morphologically distinct Bergmann fibres were observed at embryonic day E 15 in the mouse and at E 17 in the rat. Even at prenatal stages of development these fibres have a considerable degree of cytological differentiation which permits their identification as glial elements. The glial fibres contain numerous microfilaments, some smooth endoplasmic reticulum, a few mitochondria and scant free ribosomes. They penetrate the molecular and external granular layers radially and terminate with endfeet at the cerebellar surface. The proliferative cells of the external granular layer possess cytoplasmic processes which are oriented randomly, do not have endfeet, and are morphologically distinct from the Bergmann fibres with which they intermingle. In conclusion, immature Bergmann glial cells are present well before birth in the rodent cerebellum.


Ultrastructrual effects of chemical sympathectomy on brown adipose tissue. Adult rats maintained at 20-22 degrees C, were exposed to 4 degrees C for 30-60 min and injected with 50 or 100 mg/kg 6-hydroxydopamine (6-OHDA) in an attempt to achieve a similar degree of chemical sympathectomy of nerves terminating among the adipocytes and the smooth muscle cells of the blood vessels in the interscapular brown adipose tissue (BAT). After 1, 4 or 10 days the pads of BAT were removed and small sections from each pad prepared for electron microscopy; the remaining tissue was used for noradrenaline (NA) analysis for fluorescence histochemistry. Ultrastructural observations showed that 24 h after the 6-OHDA injection virtually all noradrenergic nerve terminals were distorted and contained aggregates of degenerated cell organelles. The destruction could be correlated with a disappearance of fluorescent varicosities and a reduction of measurable NA to 8-12% of the control value. There was no differential toxic effect of 6-OHDA on the terminals among the adipocytes compared to those associated with blood vessels. Thus, treatment with 6-OHDA is more effective than previous attempts using immunological or surgical methods to produce sympathectomy, because both of the latter methods only eliminate the innervation of the blood vessels and spare the nerve terminals of the adipocytes. 4 days after 6-OHDA injection there was no improvement in the morphology of the terminals but after 10 days there was an increase in the number of terminals and axons with a normal appearance and this was paralleled by an increase in extractable NA to 50% of the control value. Because of the relatively rapid recovery of NA content and reappearance of terminals of normal appearance within 10 days after 6-OHDA injection, these animals should be injected weekly when a more permanent sympathectomy of adipocytes and blood vessels is desired.


Analgesic-induced renal papillary necrosis in the Gunn rat: the comparative nephrotoxicity of aspirin and phenacetin. Homozygous Gunn rats, mutant Wistars genetically lacking glucuronyl transferase, develop renal papillary necrosis after single oral doses of aspirin and of phenacetin. The lesion appears significantly more frequently with aspirin than phenacetin, and at lower doses. The model is a convenient one with which to study analgesic nephrotoxicity.


Epignathus, double pituitary and agenesis of corpus callosum. Two infants from unrelated families died on the 1st day of life with epignathus, duplication of the entire pituitary, infundibulum and sella, and widening or separation of midline structures of the head including absent corpus callosum. We suggest that some infants surviving surgery for large epignathi may have relatively symptomless absent corpus callosum or double pituitary.


Bilirubin-associated renal papillary necrosis in the homozygous Gunn rat: light-and electron-microscopic observations. Homozygous members of the mutant Gunn strain of Wistar rats suffer an inherited autosomal recessive deficiency of glucuronyl transferase resulting in unconjugated hyperbilirubinaemia and jaundice. Unconjugated bilirubin visibly accumulated in the interstitium of the renal papillary tip. The deposit is followed by necrosis, first of intersitital cells, loops of Henle and vasa recta and later of collecting ducts. The necrotic, acellular papillary tip eventually separates. Cortical scars correlate with established papillary necrosis. The bilirubin occurs in two ultrastructural forms, crystalline and fibrillar. The deposit is found initially in the interstitium and around but not within basement-membranes. It is accompanied by cytoplasmic adaptive or degenerative changes and loss of cells by desquamation and coagulative necrosis. The lesion can be regarded as a chronic, progressive papillary necrosis similar in its evolution to the papillary necrosis of analgesic nephropathy.


The histopathology of zinc deficiency in ducks. Ducks maintained from hatching on zinc-deficient diets were retarded in growth and had severe lesions of the pedal epidermis, epithelia of the base of the tongue, oral surface of the larynx and nasal sinuses. Similar but milder changes affected the roof of the mouth, the crop and the oesophagus of a few cases. There was derangement of the architecture of the rete mucosum with loss of distinction between the cells of the stratum basale and stratum spinosum. Enlargement of the nuclei and nucleoli of these cells, widening of the intercellular space and dyskeratosis and degeneration, particularly of the prickle cells, were seen. Although epithelial atrophy occurred in early examples of the condition, acanthosis, hyperkeratosis and heterophil infiltration of the epithelial layers were characteristic of most cases. Erosion of the epithelium with the formation of purulent crusts ocntaining secondary bacterial foci was present and in these cases inflammatory phenomena occurred in the dermis. A small proportion of the nuclei of the pancreatic exocrine cells were enlarged and irregular in shape.


A review of the South American flea subgenus Ectinorus Jordan 1942, with descriptions of two new species and a key (Siphonaptera: Rhopalopsyllidae). Ectinorus (E.) chilensis sp. n. from Abracoma bennetti and E. (E.) matini sp. n. from Aconaemys fuscus are described from collections from Chile. A diagnosis for the genus Ectinorus is given and differences between the nominate subgenus and the subgenus and the subgenus Dysmicus are briefly discussed. A key to the presently recognized species of the subgenus Ectinorus is included.


Habitat and reproductive behavior of Trichinella spiralis. The normal niche of Trichinella spiralis adults was found to be in the epithelial layer of the mucosa of the small intestine of its host. Most worms were found in the epithelium at the base of the villi and in the glandular crypts. Copulation and insemination occurred between 30 and 32 hr postinfection, all although these acts were never observed, it was concluded that copulation and insemination took place in the epithelial layer of the mucosa. A majority of the adults were found to be completely embedded in the epithelium during the deposition of the motile larvae. Motile larvae were deposited in this location and from there migrated through the stroma to venules and lymphatic vessels. Male T. spiralis were found to be capable of inseminating at least 4 females.


Response of ovine prolactin-treated mice to initial infection with Trichinella spiralis. The effects of ovine prolactin on the expulsion of adult Trichinella spiralis were studied in adult virgin female mice. The results showed that ovine prolactin-treated mice had an altered pattern of worm expulsion; i.e., more adult worms were recovered from prolactin-treated mice than from normal control mice, 18 days after infection.


The effects of mebendazole and fenbendazole on Trichinella spiralis in mice. Oral administration of either Mebendazole or Fenbendazole at 50 mg/kg body weight was effective in killing a 7-hr Trichinella spiralis infection in mice. Adult worms, 72 hr postingection, were unaffected by the same dose of Fenbendazole, while Mebendazole showed partial activity. Both Mebendazole and Fenbendazole were active against developing muscle larvae. Mebendazole was effective against encysted muscle larvae while 50 mg of Fenbendazole per kg per day for 7 days from 28 days postinfection failed to have any effect on this stage of the life-cycle.


Fate of Litomosoides carinii adults transplanted into the pleural or peritoneal cavity of infected and naive multimammate rats (Mastomys natalensis). In each of 4 experiments, 58 multimammate rats (Mastomys natalensis) were subdivided into 5 groups. Thirty-four rats were infected with Litomosoides carinii and infections were allowed to become patent. Ten days after patency adult worms were surgically transferred from donor rats to each of 1 group of infected rats and 1 group of naive rats. Groups of infected and naive rats served as controls. Transfers were made either intrapleurally or intraperitoneally. Samples of blood and tissues were taken from each of 2 animals necropsied from each group at intervals to 31 days. At necropsy, the transferred worms and the original population (if any) were examined and samples were fixed. Infected rats accepted new worms with a minimum of reaction while naive rats rejected worms beginning at day 10 (intrapleural) of 17 (intraperitoneal). Rejections were complete leaving a white fibrous mass by day 24 or 31, respectively. Hemagglutination antibody titers fell into 2 groups: infected and naive. IHA titers of naive recipient rats increased into the infected range by day 3 (intrapleural) or day 10 (intraperitoneal). Microfilaria counts presented a more varied pattern but a similar lag in the intraperitoneal recipient group was observed. It was concluded that a preparation period is necessary for successful residence of adult worms, and that this preparation is not restricted to the pleural cavity.


The life history of Nezpercella lewisi Schell 1974 (Trematoda: Opecoelidae), a parasite of the northern squawfish, and the smallmouth bass. Nezpercella lewisi is an intestinal parasite of Ptychocheilus oregonensis and Micropterus dolomieui in Idaho. The miracidium develops and hatches within 12 to 14 days at 22 to 26 C or within 50 to 60 days at 12 to 15 C. Cotylomicrocercous cercariae develop in daughter sporocysts in Lithoglyphys virens and encyst in fry of Richardsonius balteatus, Rhinichthys cataractae, R. osculus, Ptychocheilus oregonensis, Cottus rhotheus, and Salmo gairdneri. Natural infections with metacercariae were found in all of the above fishes except speckled dace and trout. Squawfish were fed fry of experimentally infected redside shiner and squawfish and partially developed specimens of N. lewisi recovered 8 weeks later. The larval stages are like those of trematodes in the family Ppecoelidae to which the species is transferred.


Activity of tubercidin against immature Fasciola hepatica in mice. HaM/ICR females mice (20 to 25 g), infected with from 3 to 5 Fasciola hepatica metacercariae per os, were treated with a single dose of thepurine nucleoside analog tubercidin (7-deaza-adenosine; Tu) 7, 14, 21, and 28 days postexposure.Tu was administered either by direct intravenous injection or intraerythrocytically. Most of the flukes were killed and host survival rates were markedly increased if treatment was started within 3 weeks postexposure. The minimal single intravenous dose of Tu that was maximally effective was between 10 and 20 mg/kg.


Schistosoma mansoni: topochemical features of intrasporocyst cercariae. The carbohydrate rich filamentous coat investing the mature Schistosoma manosini cercaria affects important physiological and antigenic properties of the larval body surface. The origin of the filamentous coat and intrinsic topochemical properties of ccrcariae were investigated by fine structural and cytochemical examination of intrasporocyst larvae of various developmental stages. Staining results achieved with concanavalin A-peroxidase, bismuth subnitrate, silver protein, cationic colloidal iron, and polycationic ferritin indicate the presence of both neutral and acidic glycans at the external surface of the trilaminar tegumental plasmalemma, the latter saccharide moieties conferring upon this surface a superficial electronegative charge. The filamentous coat, apparent only on relatively well-developed larvae, is rich in neutral glycans, but fails to stain with cationic cytochemical reagents. Appearance of the surface coat occurs coincident with the differentiation of tegumentary cytons, the elaboration of carbohydrate-containing vesicles by Golgi complexes within these cell bodies, and the translocation of vesicles from sites of formation to the tegumental syncytium. It is likely that those saccharides, glycoproteins, and/or glycolipids present within the neutral filamentous coat, and those which constitute the acidic layer immediately superticial to the larval body surface, are intrinsic molecular constituents of the cercarial tegumental plasmalemma. Both the neutral filamentous coat and subjacent acidic layer may be regarded as distinct functional elements of the larval body surface glycocalyx. The molecular architecture of this membrane complex apparently reflects the specializations necessary for survival in fresh water followed by rapid adaptation to the serum environment of the mammalian host.


Helminth parasites of Rhinobatos planiceps Garman 1880, including two new species of cestodes, with comments on host specificity of the genus Rhinebothrium Linton 1890. Rhinebothrium rhinobati sp. n. and Prochristianella heteracantha sp. n. are described from the skate, Rhinobatos planiceps Garman 1880 from Chile. New host records and locations are reported for Acanthobothrium olseni Daliley and Mudry 1969, Parachristianella monomegacantha Kruse 1959, and Proleptus acutus Dujardin 1845. The genus Rhinebothrium is reported from the host family Rhinobatidae for the first time and the host specificity of the genus Rhinebothrium to the Myliobatidae is discussed.


Two tetraphylidean cestodes from the freshwater stingray Potamotrygon magdalenae Dumeril 1852 (Chondrichthyes: Potamotrygonidae) from Colombia. Two new tetraphyllidean cestodes are described from the freshwater stingray Potamotrygon magdalenae from Colombia. The new genus Potamotrygonocestus is proposed for P. magdalenensis, which differs from Pedibothrium by having a bilobed rather than X-shaped ovary, and simple rather than bifid hooks. It further differs from Pachybothrium hutsoni by having bothridial hooks inserted immediately posterior to an accessory sucker rather than inserted in the middle of a thick muscular pad. Potamotrygonocestus magdalenensis is unique among known tetraphyllideans by possessing vitellaria which are compact, cylindrical bands in the lateral portions of the middle of the proglottid. The second new species, Rhinebothrium moralarai, resembles R. scorzai by having its genital pore and terminal genitalia at the ovarian level, greatly reduced poral ovarian lobes, and by parasitizing a freshwater stingray. It differs from R. scorzai in number of bothridial loculi, testes per proglottid, and proglottids per strobila; by having quadrate rather than canoe-shaped bothridia; and by parasitizing Potamotrygon magdalenae rather than P. hystrix.


Isolation and identification of a cobamide coenzyme from the tapeworm Spirometra mansonoides. A light-sensitive vitamin B12 derivative has been extracted from the adult cestode, Spirometra mansonoides. This corrinoid was identified as the cobamide coenzyme, adenosylcobalamin, by its chromatographic, chemical, and spectral properties.


Synergistic growth promoting action of L-cysteine and nitrogen upon Hymenolepis diminuta cysticercoids in vitro. Development in vitro of cysticercoids of the cestode Hymenolepis diminuta in the presence of L-cysteine proceeded twice as rapidly under 100% nitrogen as it did with air as the gas phase. No growth was obtained with the following: D-cysteine, L-cysteine methyl ester, S-aminoethyl cysteine, L-cystine, glutathione (reduced), L-methionine, D-pantothenic acid, taurine, or thioglycolic acid; limited growth only was obtained with ascorbic acid and dithiothreitol. Homocysteine or coenzyme A was as effective as L-cysteine in stimulating the complete development of oncospheres to cysticercoids. Experiments with 14C-L-cysteine indicated that L-cysteine was perhaps incorporated into the organisms.


A new species of Leptorhynchoides Kostyler 1924 (Acanthocephala) from the pirate perch, Aphredoderus sayanus (Gilliams). Leptorhynchoides aphredoderi sp. n. is described from specimens recovered from pirate perch, Aphredoderus sayanus, collected in southeastern Louisiana. The new species is distinguished by having more longitudinal rows of proboscis hooks (15 to 18) than any other species of Leptorhynchoides. It differs additionally from L. thecatus and L. plagicephalus in having a shorter trunk, proboscis, proboscis receptacle, and proboscis hooks. Eggs of the new species are much larger than those of L. thecatus. L. aphredoderi differs further from L. plagicephalus in having fewer proboscis hooks in each longitudinal row and wider eggs. L. aphredoderi differs additionally from L. campbelli in having more proboscis hooks in each longitudinal row and much longer eggs.


Ultrastructure of interlamellar Henneguya exilis in the channel catfish. Ultrastructural aspects of interlamellar Henneguya exilis infections in channel catfish are reported. The plasmodium wall of this form differs from that of other species in that it is composed of two outer unit membranes which give rise to a zone of numerous pinocytic canals. Single-membraned canals appeared to be a stable feature of the wall while double-membraned canals are interpreted as those actively carrying out pinocytosis. Evidence suggests that host cellular cytoplasm as well as interstitial material is taken in by plasmodia. Plasmodium wall integrity, aggregation of parasite ectoplasmic components, numbers of pinocytic canals, and number of mitochondria proximal to the wall vary among different plasmodium profiles and may be related to plasmodium maturity. The parasite causes extensive hyperplasia of basal cells, which in turn replaces most other cell types found in noninfected gill filaments. Cytoarchitectural differences between basal cells of noninfected filaments and basal cells adjacent to plasmodia include significantly shorter microfilament bundles in the latter.


Davisia reginae sp. n. (Protozoa: Myxosporida) from four California marine fishes. Davisia reginae sp. n. was found in the urinary bladders of the oliver rockfish, Sebastes serranoides; quillback rockfish, S. maliger; striped surfperch, Embiotoca lateralis; and pile surfperch, Damalichthys vacca. This new Davisia belongs to the group whose lateral appendages are "solid."


Possible secretory function of the rhoptries of Eimeria magna during penetration of cultured cells. Ultrastructure of the penetration of Eimeria magna sporozoites into embryonic bovine trachea cells demonstrated that the host cell membrane was not broken during entry of the parasite. This membrane did, however, undergo alterations characterized by blebbing of vesicles, thickening, and eventual disorganization once penetration was completed. Concurrent with the entrance of the parasite into the cell, and the subsequent membrane alterations, was the appearance of empty membrane saccules, probably rhoptries, in the apical region of the sporozoite. It was proposed that rhoptry secretions aided penetration by changing cell surface characteristics which produced an eventual breakdown of the invaginated protion of the host cell membrane.


Arabinosyl nucleosides inhibit Toxoplasma gondii and allow the selection of resistant mutants. Adenine arabinoside, which inhibits the synthesis of DNA by intracellular Toxoplasma gondii, is more inhibitory to the parasite than it is to cultured human fibroblast host cells. A single-step mutant of T. gondii that is 50-fold more resistant to adenine arabinoside was isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. Cytosine arabinoside is notably more inhibitory to cultured human cells than it is to T. gondii. Thus in infected cells treated with cytosine arabinoside and labeled with 3H-deoxyuridine nearly all of the label is specifically incorporated into the intracellular T. gondii.


Distal neonatal intestinal obstruction: the choice of contrast material. The use of barium sulfate as the contrast agent of choice in the radiographic evaluation of distal neonatal intestinal obstruction is advocated. The advantages of Gastrografin or other water-soluble contrast materials are far outweighed by their disadvantages, which include the hazards of hypertonic dehydration and the danger of missing the diagnosis of Hirschsprung's disease. Five patients are presented, all of whom had the diagnosis of Hirschsprung's disease missed in the neonatal period with one use of Gastrografin enemas. All five were subsequently admitted to the Surgical Neonatal Intensive Care Unit, critically ill with enterocolitis of Hirschsprung's disease.


Congenital laryngotracheosophageal cleft. Two infants with complete laryngotracheoesophageal cleft are presented. One infant had hypoplasia of the left bronchus and lung and the other had a cystic dysplastic right kidney. The literature is reviewed and a scheme for managing infants with this severe and as yet lethal anomaly is presented.


Long-term follow-up of patients with congenital diaphragmatic hernia. A long-term follow-up was carried out on 30 patients who had congenital diaphragmatic hernias operated on over a 21-yr period. The review took the form of clinical examination, chest x-rays, pulmonary function tests, and lung scans. Lungs that were hypoplastic at birth remained underdeveloped as judged by pulmonary function tests and hypoperfusion on lung scan; however, children who survived birth6 and operative repair went on to live normal lives through the period studied. There was some suggestion from pulmonary function tests and lung scans that in the older group a preemphysematous state may exist but this was asymptomatic. There was no evidence of increased susceptibility to respiratory infection in the group. Ten per cent of the children were mentally retarded, evidently from hypoxia after birth.


Use of clindamycin and gentamicin in pediatric colonic surgery. The combination of clindamycin and gentamicin was used to treat 25 pediatric surgical patients. In 9 of the 11 patients with perforated appendicitis, B. fragilis was isolated from the peritoneal cavity. There was a rapid clinical response to treatment in all cases. No side effects were observed. Clindamycin and gentamicin seem to be the antibiotics of choice for such infections.


Development of the lung in fetal rabbits with experimental diaphragmatic hernia. Congenital diaphragmatic hernias were successfully produced in fetal rabbits. The lungs of these animals remained small and hypoplastic on gross examination, although histologically they have matured significantly from the original pseudoglandular stage. It is our impression that the so-called hypoplastic lung in diaphragmatic hernias is small in size but potentially functioning when relieved of compression.


Carcinoma of the colon in children: a report of six new cases and a review of the literature. Of six children with carcinoma of the colon, none had ulcerative colitis or a family history of carcinoma of the colon or colonic polyposis. In 75 cases traced in the literature, a common early symptom of carcinoma of the colon in children is acute, crampy abdominal pain. At laparotomy for suspected appendictis, the possibility of the acute pain being due to carcinoma of the colon should be borne in mind. Otherwise the symptoms of carcinoma of the colon in children do not differ substantially from those in adults. The prognosis is unfavorable; in only 2.5% of the cases on record did the children survive 5 yr after the operation.


Peritoneal lavage in children with blunt abdominal trauma. Quantitative peritoneal lavage was performed in 52 children with blunt abdominal trauma to determine the presence of intraabdominal injuries. A strongly positive lavage was 100% accurate in diagnosing an intraabdominal injury requiring operation. A negative lavage demonstrated absence of a significant intraperitoneal injury with 100% accuracy. A weakly positive lavage was not diagnostic and required additional evaluation including intravenous pyelography echography, and arteriography. Diagnosis and treatment was prompt, and in 20 of 21 cases, operation was performed within 4 hr. Peritoneal lavage was found to be safe and much more accurate than physical examination in diagnosing significant intraabdominal injury.


An in vivo mass spectrometer system for the continuous monitoring of Po2 and Pco2. A mass spectrometer blood gas catheter system for the continuous in vivo analysis of Po2 and Pco2 has been presented. This system has been experimentally evaluated and demonstrated to be reliable and reproducible over a period of 30 hr following insertion of the catheter in the abdominal aorta. Although the present catheter design does not allow insertion through an existing umbilical arterial line in neonates, a clinical evaluation will be undertaken when a more flexible catheter becomes available.


Lymphoid hyperplasia of the bowel and its surgical significance in children. Twelve children with abdominal complaints had lymphoid hyperplasia of the bowel presenting in an acute or chronic form. The etiology is obscure. An infectious process is thought to precipitate the acute form of the disease. Parasites were identified in two patients with the chronic disease. The acute form, with involvement of the appendix or terminal ileum, presents commonly as acute appendicitis. Because of its self-limiting nature, appendectomy with perservation of the terminal ileum is appropriate. When intussusception is present, resection of the ileum is advisable. The chronic form, which is also common in the terminal ileum, produces disabling symptoms, recurrent intussusception, chronic anemia, and weight loss and is, therefore, amenable to surgical resection.


The predictive efficacy of three MMPI short forms. In order to investigate the predictive efficacy of three MMPI short forms, the standard form answer sheets of 50 inmate volunteers and 44 clinic outpatients were scored separately for Faschingbauer's, Hugo's and Mini-Mult scales. T-score correlations and t tests between the standard form and each short form, as well as comparisons using Lacks' criteria were reported. Results indicated that the Faschingbauer form was superior to the other two forms. Results were discussed in terms of the populations tested and in reference to the different methodologies used in developing each of the short forms.


A Jungian approach to the Rorschach: an exploration of differing patterns of aggression. Rorschach responses of institutionalized adolescent males exhibiting different patterns of aggressive behavior were analyzed from the perspective of Jung's archetypal psychology. Distinct differences in the individual's relationship to archetypal processes were found and were consistent with the behavioral expression of aggression. The study supports McCully's view that Rorschach  plates have a potential capacity to stimulate the archetypal structure of the psyche with the resulting archetypal energies influencing the perceptual experience of the observer in lawful and ordered ways. The relationship to archetypal influence is an important but often neglected factor in the adolescent's task of becoming a separate and individual personality. A rich commentary on each individual's protocol by Professor McCully is included to more fully illustrate the archetypal approach to Rorschach symbolism.


Interpretive accuracy of abbreviated MMPIs. The interpretive accuracy of the standard MMPI and three abbreviated forms was assessed and compared with a sample of psychiatric inpatients. Psychiatric teams evaluated the accuracy of the interpretation of one abbreviated form and the standard form for their patients. Only the MMPI-168 obtained comparable ratings to the standard form.


Gender roles and human sexuality.

Gender roles and human sexuality. Personality differences among three self-ascribed render-role types (predominantly masculine, predominantly feminine, or no predominant orientation) were investigated within a group of 128 male and female homosexuals. The results, utilizing the Adjective Check List (ACL) and a specially designed questionnaire placed all groups within +/- one standard deviation of the mean on all ACL scales except abasement. A multiple discriminant analysis demonstrated that 10 of the ACL scales significantly discriminated between self-ascribed gender-role types. It was suggested that homosexuality may be appropriately conceived of as an alternate life style rather than a noslogical entity, and that gender-role may, in some instances, be more important than biological sex as regards one's self perceived personality characteristics.


Test-retest reliability of the Rorschach on neurologically impaired subjects. Pairs of Rorschach protocols for each of 25 neurologically impaired patients were obtained from two different testings spanning an average of three years apart to study the Rorschach's test-retest reliability under specific conditions. Significant correlations were obtained for all but a few major summary scores. An additional analysis revealed no strong relationship between the varying test-retest interval lengths and the stability of various Rorschach scores.


The effects of marijauna on verbalization and thought processes. The verbal output of subjects in response to 10 cards of the TAT was obtained on two occasions and under placebo, marijauna low and high conditions. The themes were independently rated on 13 variables reflecting thought processes, emotional tone, control aggression, and sexual content by two judges. Significant differential dosage differences were obtained in terms of disruption of cognitive processes, and emotional tone. Moreover, a multivariate analysis yielded a significant discrimination among the three experimental conditions.


Responses of adolescent, middle-aged, and aged females on the Gerontological and Thematic Apperception Tests. The Gerontological and Thematic Apperception Tests were administered to adolescent, middle-aged, and aged non-institutionalized females with 30 subjects in each age group. Content of themes elicited did not differ between age groups for each test nor was the GAT found superior to the TAT in eliciting themes reflecting problems of the aged as claimed by authors of the GAT.


Trait and type differences among male and female assaultive and nonassaultive offenders. Trait and type differences, defined by MMPI scale scores and profiles, of offenders arrested for misdemeanor assaultive and nonassaultive offenses were investigated. The subjects were male and female offenders who were found guilty by the courts and sent to a clinic for a dispositional evalution. Only the Ma Scale showed a significant difference between assaultive and nonassaultive male offenders. Assaultive female offenders were lower than nonassaultive females on the Hy and Mf Scales. In addition, the 4-3 MMPI profile had the smallest percentage of assaultive offenses while the 4-8 profile had the largest. The results do not support the existence of a single, clearly defined set of traits or profile type that is involvedin an assaultive offense.


Length of male and female friendship and perceived intelligence in self and friend. The Self-Rating Scale of Intelligence (SRSI) and the Otis  intelligence test were administered to -20 pairs each of same-sex long-acquaintance males and females and 12 pairs each of same-sex short-acquaintance males and females. The SRSI provided subjects with the opportunity to make intelligence attributions to self, friend, and ideal friend and to provide the expected rating of self by the friend and people-in-general. Significant positive correlations were obtained from relating the within-person perceptions, while nonsignificant correlations were obtained from the relation of perceptions and objectively measured intelligence between friends. Self-concept support from the friend and from people-in-general were the more significant relationships identified across groups.


Social influence processes and the outcome of sensitivity training. Prediction were tested as to the persistence of change after sensitivity training. Using concepts derived from kelman, it was predicted that internalizers will show most durable benefit from training, whereas externalizers (compliants and identifiers) will show less. Questionnaire measures were used based on sociometric rankings of influence sources during training. The subjects were 199 professionals of mixed sex and age attending 5-day sensitivity training programs in England. As predicted, at the close of training internalizers did not differ from externalizers on ratings of benefit by self or by other trainees. Trainers rated internalizers higher (p less than .05). Five months later, internalizers were rated higher than externalizers on benefit by self (p less than .01), and there was a trend in the same direction for ratings by others. Between the two testings of externalizers' benefit there were significant decreases for self-benefit rating (p less than .01) and other-benefit rating (p less than .01), whereas internalizers showed no significant decrease. The findings support typological approaches to the study of social influence and underline the need for caution in selecting the criterion measures to be used immediately after sensitivity training.


Bystander reactions to a violent theft: crime in Jerusalem. Seventy-two male Israeli students were exposed to a violent crime in the course of a bogus discussion. Their awareness of other bystanders' lack of reaction to the emergency (social influence) and others' awareness of their actions (evaluation apprehension) were crossed in a 2 X 2 factorial design. An "alone" condition in which the subject was the only bystander controlled for the effects of others' mere presence (diffusion of responsibility). Helping was reduced by diffusion of responsibility and slowed by negative social influence but was increased by evaluation apprehension. Differences traceable to social influence appeared prior to those from the other processes. Implications of these findings for the measurement of helping and the interpretation of bystander decision making are discussed.


Effects of being observed on expressive, subjective, and physiological responses to painful stimuli. Two experiments explored the effects of observation by another on responses to painful stimuli. It was anticipated that the intensity of pain-related non-verbal expressivity decreases under observation, while indices of arousal (skin conductance and self-report) increase. In Experiment 1, subjects' expressive responses to shock were attenuated when subjects were observed as compared to when they were alone, but the anticipated augmentation of arousal did not occur. Rather, the attenuation of expressive behavior was accompanied by a general decrease in subjective and autonomic responses to the painful stimuli. A second experiment replicated the results of the first study and, in addition, found no evidence for a differential impact of sex of observer on the three measures of arousal. An interpretation is discussed for the effect of observation on expressive behavior and for the relationships observed among expressive, autonomic, and subjective indices of pain.


Targets of gazing and eye contact during interviews: effect on Japanese nonverbal behavior. The gaze direction of both the subject and his interviewer were varied independently, such that either looked at the other's eyes or at the other's knees in a 2 X 2 design. A repeated measures design was used with nonverbal vehaviors of Japanese manes as dependent variables. When the interviewers gazed at the subjects' eyes, the response latencies of the subjects were shortened and their torso movements were reduced. Results from other studies of Japanese nonverbal behavior suggest that this pattern of response indicated greater subject invlovement in the interaction. The magnitude of these effects was unchanged whether the subject was reciprocating the interviewer's gaze and making eye contact or looking at the interviewer's knees. It was thus reasoned that effects produced by eye contact in other research may have resulted from subjects' knowledge that they were being gazed at and not from the unique properties of eye contact. When the subjects gazed at the interviewer's eyes, the hand self-manipulations of the subjects increased, reflecting the upsetting effects of monitoring the interviewer's face during interaction. The consequences of gazing at another's eyes thus appear to be different from having one's eyes gazed at by another.


Psychological factors and clinical observations in acupuncture analgesia and pain abatement. The present study attempted to (a) replicate findings on acupuncture reported in the Chinese literature; (b) investigate the effects of acupuncture in achieving analgesia and pain abatement; and (c) isolate the relevant psychological and/or physiological variables involved. Fifty volunteer men and women between 18 and 30 years of age were administered the acupuncture phase of this study for induction of analgesia and relief of pain in the oral cavity. A comparable group of 30 additional Ss were included in the study for comparison with the acupuncture group on several objective psychological measures. Forty of the acupuncture Ss were classified as totally successful. No significant differences between the acupuncture group and the comparable control group were obtained on the objective psychological measures, including measures of personality, suggestibility, anxiety, and attitudes. The results appear to indicate that psychological factors are minimally involved in obtaining analgesia and pain abatement with acupuncture techniques. Several interesting clinical observations were noted during the acupuncture procedure, including absence of discernable signs of analgesia, consistency of results, contralateral analgesic effect related to the location of acupuncture needles, etc. These results were discussed in terms of the possible role of physiological and psychological factors in acupuncture. Possible areas of future research were also discussed.


The consequences of positive and negative perceptual identification. This study tested the consequences of positive and negative perceptual identification under conditions where the other person (C) represented an ideal or threatening aspect of the Ss' identity. One hundred male students (17 to 25 years of age) participated in the experiment, which followed a 2 X 2 X 2 factorial design. The C was presented as either similar or dissimilar to the Ss and as successful or unsuccessful in an important exam that they were about to take. The other variable was presentation of the C as a co-worker or unrelated other. Attitudes towards the C and imitation of his choices in a person perception task were the dependent variables. As predicted, positive perceptual identification with the C led to further identification and positive feelings toward him. The hypothesis that negative perceptual identification would be followed by behavioral differentiation was not confirmed, although there was some evidence to suggest that Ss tended to deny similarity with the C in this situation.


Further observations on the psychometric properties of the Psychological Effectiveness Scale. Previous work by Poe and by the present writer have shown that the Psychological Effectiveness Scale (PES) has sufficiently high validity and reliability to justify continued research on the instrument. In an attempt to study further the psychometric attributes of the PES, 54 American men and women volunteer methadone clinic patients were assigned a wider range of rating tasks than had hitherto been used. The Ss rated themselves under six different instructions. Internal consistency reliability, measured by coefficient alpha, was in the .90s in all ratings. The differences between the means of some of the ratings were significant at the .01 level. Average item-correlation (total minus item) was also high. These findings, consistent with the results of earlier work, confirm the reliability and construct validity of the PES.


The relationship of extraversion and neuroticism to two measures of assertive behavior. One hundred forty-four college students completed the Eysenck Personality Inventory and the Rathus Assertiveness Schedule (RAS) and wrote their behavioral reactions to five scenarios in which an assertive behavior was an appropriate response. Extraversion showed a significant positive correlation with the RAS in both males and females. Neuroticism was negatively correlated with RAS in both sexes. Extraversion and RAS correlated significantly with rated Assertiveness in the scenarios only in the male sample. The RAS predicted variance in Assertiveness beyond that predicted by Extraversion. Overall low correlations of the measures with rated Assertiveness were discussed in terms of the low internal consistency reliability of that scale.


Psychometric properties of the Self-Rating Depression Scale (SDS). While there are data supporting the content and construct validity of the Self-Rating Depression Scale (SDS), the evidence regarding its reliability is not conclusive. For the purpose of exploring the psychometric properties of the SDS, two studies were done using Ss from two markedly different socio-cultural settings: 213 male and female drug addicts in New York City and 206 male and female undergraduates in Nigeria. Findings included high coefficient alphas and large average item-correlations (total minus item) in both studies. It was concluded that the SDS rates well in terms of internal consistency reliability and construct validity.


Inference of word meaning from syntax structure by normal children and retarded adolescents. Children from five to 12 years of age (N = 136 boys and girls) and institutionalized retarded adolescents (N = 30 boys and girls) were given a task developed by Brown to test ability to infer nonsense word meanings from syntactic clues. Response accuracy for the normal children was consistently low from five years up to eight years of age, after which it increased steeply with increasing age. However, accuracy levels were markedly below those reported by Brown and raise questions concerning his original finding that young children are largely successful in using the grammatical context of new words to guess their meaning. Performance of the retarded adolescents did not parallel that of the nonretarded children, and on two of the three parts of speech their performance fell below mental age expectations, a result attributed to their deficient generalization ability.


Success, failure, and self-other orientations. The experiment investigated the effects of success and failure experiences on Ss' subsequent ratings in a symbols task measure designed to examine perceptions of self-other orientations. Sixty male and female adolescents were assigned to success, failure, or control experiences on three achievement tasks ostensibly testing intellectual ability. Posttest minus pretest changes were assessed on variables of self-esteem, social interest, egocentricity, power, and individuation as measured in the symbols tasks, and analyses of variance results were examined for differences among Ss in the success, failure, and control conditions. As hypothesized, Ss in the success condition made significantly more positive changes in self-perceptions of esteem, social interest, and power relative to failure and control Ss. Implications of the findings were discussed for social psychologists and clinicians interested in personality assessment and social functioning.


Sex and race as factors affecting the attribution of insanity in a murder trial. Two hundred and eight white male and female college students read a summary of a case of a violent murder in which an insanity plea was entered. The sex and race (black or white) of the hypothetical defendant was varied in a 2 X 2 factorial design with 52 Ss per cell. Measurements included verdict (guilty or insane), length of recommended sentence, and ratings of certain defendant characteristics. Major results were as follows: (a) harsher treatment of males as indicated by longer sentences, (b) longer sentences for white as opposed to black males among defendants found guilty, and (c) a trend toward a higher proportion of guilty verdicts for black males.


Eimeria tenggilingi sp. n. from the scaly anteater Manis javanica Desmarest in Malaysia. Eimeria tenggilingi is described from the pangolin or scaly anteater, Manis javanica, in Malaysia. The spheroid to subspheroid oocysts average 18.9 X 17.8 mum. The oocyst wall is composed of 3 layers, each approximately 0.6 mum thick. The 2 outer layers are striated and yellowish green. The inner layer is dark brown. One or 2 polar granules are present, but an oocyst residuum is absent. Ellipsoid sporocysts average 12.4 X 6.2 mum. A sporocyst residuum is present. This is the first Eimeria species reported from a host in the order Pholidota.


The genus Leptotheca (Protozoa: Myxosporida) in macrourid fishes and sablefish, Anoplopoma fimbria. Five species of Leptotheca, one new, were found in the macrourid fishes and the sablefish, Anoplopoma fimbria. Those species which were geographically widespread in numerous host species showed little variation. Two Leptotheca species were found both in the gall bladder and urinary bladder/kidney.


Quantitative ultrastructural investigations of mitochondrial development in Leishmania donovani during transformation. The ultrastructure of the mitochondrion during transformation of Leishmania donovani from amastigote to promastigote stages was studied by morphometric analysis. There was a slight but significant decrease in relative mitochondrial volume (Vvmi) during transformation. This decrease was linear with time for at least 27 hr. No change in relative lipid inclusion volume (Vvli) was observed during transformation. The ratio of inner to outer mitochondrial surface membrane densities (Svmii:Svmio) also remained unchanged. Although the relative number of cristae remains unchanged after transformation, there is an increase in cristae number in the portion of the kinetoplast opposite the flagellum.


Comparative in vitro development of precocious and normal strains of Eimeria tenella (Coccidia). Eimeria tenella strain Wis-F is known to develop in chickens with a significantly shortened prepatent period and its pathogenicity is virtually completely attenuated. In vitro development of this strain paralleled development of the control (Wisconsin) strain through the first asexual generation. Instead of entering 2nd generation schizogony, however, most of the Wis-F merozoites developed into microgamonts or macrogamonts. Wall-forming bodies were prominent in developing macrogametes at 80-88 hr and began coalescing into the oocyst wall by 88 hr. Microgamete development paralleled that of macrogametes, with the appearance of multinucleate, immature forms at 72-80 hr and with recognizable, spermlike microgametes being prominent at 88-96 hr. Pathogenicity attenuation and reduction of the length of the prepatent period clearly resulted from omission of a portion of the life cycle (2nd generation schizogony).


Feline toxoplasmosis from acutely infected mice and the development of Toxoplasma cysts. The development of Toxoplasma cysts was studied in mice inoculated with tachyzoites by several routes. After 1-30 days of infection, murine tissues were examined microscopically and portions or whole carcasses were fed to mice and cats. The feces of the cats were examined for oocyst shedding. Cyst-like structures containing distinct PAS-positive granules were first seen after 3 days of infection with tachyzoites, and became numerous by 6 days. Argyrophilic walls were first seen after 6 days, and became numerous by 16 days of infection with tachyzoites. Prepatent periods to oocyst shedding (PPO) were either "short" (3-10 days) or "long" (19-48 days). The "short" PPO was found only in cats that had ingested mice infected for 3 days or longer, and was related to the development of PAS-positive granules in T. gondii, and to high, 60-100%, oral infectivity rates for cats. The "long" PPO followed the ingestion of mice infected for only 1-2 days, and was related to tachyzoites without distinct PAS-positive granules and low, 32% or less, infectivity for cats. The "long" PPO followed also the ingestion of oocysts and the parenteral inoculation of tachyzoites, bradyzoites, or sporozoites. Using the "short" PPO as a criterion for detecting cysts in tissues, it was shown that (a) numerous cysts developed in mice 5 days after inoculation with tachyzoites, 7-9 days after inoculation with cysts, and 9-10 days after inoculation with oocysts, and (b) cysts developed faster and more frequently in the brain and muscle than in lungs, liver, spleen, and kidneys of mice inoculated with tachyzoites.


Prevalence and morphology of Eimeria gadi (Fiebiger, 1913) in the haddock. The coccidian parasite Eimeria gadi was found in the haddock, Melanogrammus aeglefinus, taken from the Nova Scotian fishing banks. The haddock infection rates ranged from a high of 58% on Emerald Bank to a low of 4% on Georges Bank, the average being 32%. There was no relationship between sex and degree or prevalence of infection. Although the probability of an occurrence of infection increased with size, small fish with heavy infections were observed. The degree of infection had no apparent effect on the condition factor (length/weight) of the fish. The infection rate reached a maximum in the fall of the year while the heaviest infections were observed in the spring. It is evident from the data that the infection is fatal. The parasite mass, appearing as a creamy viscous to a yellow semisolid material in the swimbladder, consisting of various parasite stages, fibrous and cellular debris, and lipid material. Some aspects of the sporocyst stage are described. No other gadoids from the Nova Scotian banks were found to be infected; however, a single specimen of the fourbeard rockling, Enchelyopus cimbrius, from St. John's, Newfoundland, was found to be heavily infected with E. gadi.


Pulse-labeling of kinetoplast DNA: localization of 2 sites of synthesis within the networks and kinetics of labeling of closed minicircles. Short pulse-labeling of log phase Crithidia fasciculata cells with [3H]thymidine allowed the autoradiographic visualization of 2 sites of replication of kinetoplast DNA situated at the periphery of the networks and separated by 180 degrees. Longer pulse-labeling led to the previously reported total peripheral labeling pattern. Pulse-labeled networks possess an intermediate density in ethidium bromide-CsCl equilibrium gradients between the densities characteristic of closed networks and open or linear DNA. Removal of ethidium bromide by several methods and treatment of intermediate band networks with RNase and pronase had no effect on the equilibrium rebanding pattern. Closed minicircles of Leishmania tarentolae are not labeled by a short pulse of intact cells with [3H]thymidine. A chase of approximately 3-4 hr is required for the appearance of radioactivity in closed minicircles, a time delay which implies the existence of intermediate events between replication and eventual covalent closure of the minicircles.


Cessation of nuclear DNA synthesis in differentiating Naegleria. DNA synthesis during growth and differentiation in Naegleria gruberi strain NEG populations has been studied. Autoradiography of cells labeled with [3H]thymidine revealed that grains are concentrated over the nuclei in logarithmically growing populations of cells, whereas in differentiating cells, grains are scattered over the cytoplasm; i.e. no significant nuclear labeling is detectable. It was established by MAK chromatographic analysis that [3H]thymidine is incorporated into double-stranded DNA in Naegleria and that the actual amount of incorporation in the logarithmically growing populations of cells is 20 times greater than that in differentiating cells. These results suggest that nuclear DNA synthesis is reduced markedly soon after the initiation of differentiation, while cytoplasmic DNA synthesis continues. It was established from cell cycle analysis that the approximate intervals of G1, S, G2, and M phases were 180, 183, 90, and 28 min, respectively. Hence, the reduction in the nuclear DNA synthesis in differentiating cells is not due to the inhibition of initiation of DNA replication, but rather to the termination of the DNA replicating process. Thus DNA synthesis is curtailed in the presence of RNA and protein synthesis which are required for differentiation.


Enzymes of carbohydrate metabolism in four human species of Leishmania: a comparative survey. The occurrence and levels of activity of various enzymes of carbohydrate catabolism in culture forms (promastigotes) of 4 human species of Leishmania (L. brasiliensis, L. donovani, L. mexicana, and L. tropica) were compared. These organisms possess enzymes of the Embden-Meyerhof pathway but lack lactate dehydrogenase. No evidence could be found for the production of lactic acid by growing cultures and lactic acid could not be detected either in cell-free preparations or after incubation of cell-free extracts with pyruvate and NADH under appropriate conditions. All 4 species possess alpha-glycerophosphate dehydrogenase and alpha-glycerophosphate phosphatase which together could regenerate NAD, thus compensating for the absence of lactate dehydrogenase. The oxidative and nonoxidative reactions of the hexose monophosphate pathway are present in all 4 species. Cell-free extracts have pyruvate dehydrogenase activity which allows the entry of pyruvate into and its subsequent oxidation through the tricarboxylic acid cycle. All enzymes of this cycle, including a thiamine pyrophosphate dependent alpha-ketoglutarate dehydrogenase, are present. Both NAD and NADP-linked malate dehydrogenase activities are present. The isocitrate dehydrogenase is NADP specific. There is an active glutamate dehydrogenase which could compete with alpha-ketoglutarate dehydrogenase for the common substrate (alpha-ketoglutarate). Replenishment of C4 acids is accomplished by heterotrophic CO2 fixation catalyzed by pyruvate carboxylase. All 4 species have high levels of NADH oxidase activity. Several enzymes thus far not found in any species of Leishmania have been demonstrated. These are: phosphoglucose isomerase, triose phosphate isomerase, fructose-1, 6-diphosphatase, 3-phosphoglycerate kinase, enolase, alpha-glycerophosphate dehydrogenase, alpha-glycerophosphate phosphatase, pyruvate dehydrogenase complex, citrate synthase, aconitase, alpha-ketoglutarate dehydrogenase, glutamate dehydrogenase, and NADH oxidase.


Black children's perceptions of black english. In studying the perception of differences between Black English and Standard English by 48 first-grade, urban, Black children, BE and SE were partitioned into content, i.e., syntax and lexicon, and style, i.e., suprasegmentals or prosodic features of phonology. A discrimination task was designed to test whether the subjects could perceive differences in terms of style or content or both. Accurate discriminations were related to language variety preference and school and home-street register maintenance. The results indicated BE style to be as significantly related to BE preference and register maintenance as BE content when the two were separated.


[The value of double contrast radiological exploration in the study of pathological appearances of the greater curvature of the stomach (author's transl)]. The authors indicate the special points relative to effective double contrast radiological exploration of the greater curvature of the stomach (high titre barium suspension, with high covering power; maximal insufflation of the gastric cavity; decubitus films always complemented by filling images in procubitus and in a vertical position. They then present the principal features which may be encountered using the method: -addition images in relation with ulcerated lesions; -lacunae indicative of localised parietal proliferation; - "double contour" appearances corresponding to infiltrating tumors with a broad surface; - "thick folds" of the greater curvature which, apart from the classical causes, should first suggest an inflammatory or tumoural process in the underlying pancreas; - extrinsic imprints, the topographical location and appearances of which may indicate their origin.


[Double contrast exploration of the stomach after surgery (author's transl)]. The authors describe the application of double contrast radiological exploration in the stomach after surgery. They show normal and pathological results after the principal types of gastric surgery: excisions, conservative procedures, hiatal hernia surgery. Apart from the post-operative period, the technique may be used without major difficulties. The precise images obtained render it the technique of choice for the detection of the organic complications of gastroduodenal surgery.


[Angiographic aspects of portal hypertension in children (author's transl)]. Arterial portography is an easy and safe method for the study of children presenting signs of portal hypertension. This method permits the exact localisation of the site of obstruction, the demonstration of the degree and extent of the collateral vessels as well as an appreciation of the intrahepatic arterial bed. A more adequate therapeutic attitude can thus be defined.


[Radiological implications of iatrogenic complications in neo-natal surgery (author's transl)]. The authors report 17 cases of iatrogenic complications occurring during the neonatal period over an interval of 5 years in a surgical service. Such complications concern the radiologist, either in their cause or their discovery. These cases are taken together with findings reported in the literature and lead the authors to draw conclusions with regard to the practical management of certain examinations in the neonatal period and the radiological surveillance of the newborn in a surgical department.


[Angiographic signs of the small intestine (two cases) (author's transl)]. The authors describe 2 cases of ileal carcinoid. They evaluate the advantages of selective angiography over the traditional radiologic methods, considering their cases and the 39 found in the literature. The angiographic signs of the lesions localized to the bowel wall are rather scarse and non-specific. The signs of mesenteric infiltration, which is precocious and conspicuous in this type of tumour, are more significant. Liver metastases, which are very frequent, are hypervascularized. The angiographic pattern may be similar to that found in some inflammatory diseases, but can be differentiated from that of other neoplasms of the small intestine.


[Atypical angiographic appearances of aneurisms of the abdominal aorta (author's transl)]. On the basis of 72 radio-surgical cases of abdominal aortic aneurism, the authors stress the value of atypical angiographic findings, which are ten in number. The presence of clot within the aneurism itself may explain a disparity between radiological and surgical findings. Failure to recognize these atypical signs is very serious, when the diagnosis of aneurism is not suspected clinically. Antero-posterior and, above all, lateral abdominal aortography is essential in the angiographic study of aneurisms of the abdominal aorta. Careful search for these 10 atypical signs should make it possible to avoid missing latent aneurisms. Lateral abdominal aortography is essential in order to determine the state of the abdominal collaterals of the aorta and, in particular, the superior mesenteric artery.


[Spontaneous sub-capsular haematoma of the liver compressing the hepatic veins. Angiographic diagnosis (author's transl)]. Apart from special types encountered in neonates and during pregnancy, spontaneous sub-capsular haematoma (SCH) of the liver is a rare condition which is usually not recognized before operation. The diagnostic value of arteriography is emphasized by this case of SCH in a 29 year old man which presented spontaneously with the appearance of a large mass in the right hypochondrium with fever and pain. Angiographic changes identical to those seen with a traumatic SCH were found and, in this case, were accompanied by a local reversal in intra-hepatic portal flow related to a tumoural Budd-Chiari phenomenon (compression of the hepatic veins by the haematoma). Despite histological study of the liver, no tumoural, vascular, infective or parasitic aetiology could be found to explain this apparently idiopathic spontaneous SCH.


Following advice in general practice.

Following advice in general practice. A random sample of 521 patients to whom prescriptions had been issued in an urban general practice were investigated to see how well they followed advice about taking medicines.Most factors that have been previously reported as affecting this did not appear to do so. A very high degree of compliance was achieved and it is suggested that the key factor in this is the relationship between doctor and patient.


An audit of the care of diabetics in a group practice. The diabetics in a general practice of 20,175 patients were identified during one year and 119 were found-a prevalence of 5.9 per thousand.The age and sex distribution, method of treatment, criteria of diabetic control, complications, and present method of care were analysed from the medical records to examine the process of medical care of a chronic disease in general practice.


Army families and the general practitioner. The military component of a rural general practice is described with details of increased workload and morbidity for conditions associated with emotional stress.


Developmental and paediatric care of the pre-school child. Through an Upjohn Travelling Fellowship I visited 27 experts in childcare and sought their opinions on the privileges, possibilities, and problems in organising developmental and paediatric care for pre-school children in the United Kingdom.The role of the general practitioner was seen by many of the experts clearly. How he is to play it is shrouded in uncertainty. Research is urgently needed both on the tools of surveillance and on the different methods of arranging care.


Rubella immunisation and contraception--a case for re-examining the policy of the Department of Health and Social Security. Now that immunisation against rubella is available, it would at first sight seem reasonable to identify all potential mothers susceptible to this disease and immunise them. Preliminary screening, however, carried out in order to restrict vaccination to seronegative subjects, not only serves no useful purpose, but is counter-productive.


The cost of a general practitioner in the national health service. This paper estimates the cost to the National Health Service of decisions made by a trainee general practitioner during two consecutive weeks. By extrapolation of the cost of these actions (issuing prescriptions, issuing National Insurance certificates, requesting investigations, and initiating hospital referrals), the annual cost of a general practitioner in the National Health Service is at least pound43,000.


General practice in Croatia, Yugoslavia. The position and importance of general practice in the Yugoslavian Health Service is being reviewed in a study of the working conditions, the composition and relationship of the primary health care team, the workload, and the opinions of the patients in Croatia, Yugoslavia.We found that many practices had barely half the recommended equipment, that the average workload was 40 patients a day, and that many general practitioners expected others to improve their organisation rather than undertaking it themselves.Those general-practitioner teams which we rated highly were also the most popular with patients. The job satisfaction of nurses varied and was highest when the doctors in the team did not have a high need for status for themselves.We consider general practice to be of crucial importance in the total system of health care in our country and believe that general practitioners should have the same status as specialists.


Current concepts of defibrination in the pregnant woman. The possible predisposing causes of difibrination in the pregnant woman are discussed. Coagulation profiles and qualitative and quantitative assessment of fibrinolytic activity during labor, delivery and the early puerperium in normal pregnancies are presented. These factors were also studied in patients with abruptio placentae and prolonged intrauterine fetal death and in women whose pregnancies were terminated with intraamniotic infusion of hypertonic saline or prostaglandin F2alpha. The findings suggest that a minor degree of physiologic defibrination develops during normal labor that is qualitatively similar to, but of much lesser magnitude than, the pathologic defibrination syndrome commonly associated with abruptio placentae or prolonged intrauterine fetal death. Some degree of defibrination occurs in women undergoing saline abortion, similar to that of women during normal parturition, but does not usually reach clinically significant levels. The coagulation changes seen during prostaglandin abortion suggest that a minor degree of defibrination occurs that is substantially less than that seen during saline abortion. The findings presented form a basis for  the rational management of defibrination in the pregnant woman.


Rape: the gynecologist's role.

Rape: the gynecologist's role. The rape victim is a product of both a sexual and violent crime; the patient, in becoming the gynecologist's responsibility, must be received in a manner uniquely adapted to fit this situation. The physician must maintain his or her role as a healer and has no place acting as a lawyer or law enforcement officer. However, by obtaining the necessary, basic knowledge of the community's law, the physician can enable the patient to avoid unnecessary personnel, who tend to interview her at the most traumatic moment. It is best to do the minimum needed so that the patient realizes she is being treated as a troubled individual and not as a part of a future medicolegal case. In addition, the physician can practice good preventive medicine by alerting patients to clues about how to avoid rapists' attacks and yet do all they can to prevent the injuries which, although not primary, are part of many rapes. Our patients need a friend, a physician and a counselor all in one. The gynecologist should be all three.


Colposcopic evaluation of cervical intraepithelial neoplasia. Colposcopic examination and directed biopsies were performed on 70 patients with abnormal cerivcal cytology. The correlation of the histology of the directed biopsies with the colposcopic appearance was 80%; it was 86% with the original Papanicolaou smear. In no case was the histology of a subsequent cone biopsy or hysterectomy specimen more advanced than that of the directed biopsy. Conization was avoided in 52 of the 70 patients and could have been avoided in seven others.


Perforation of the large bowel by a Dalkon Shield intrauterine device. Since the introduction of the Dalkon Shield, there have been many reports on serious complications of this intrauterine divice (IUD). After the publication by Christian, the manufacturer voluntarily suspended manufacture of the Dalkon Shield. Nevertheless, many women are still using this IUD for contraception. This paper represents one of the firsts reports in the literature on the perforation of the sigmoid colon by a Dalkon Shield.


Coexistance of tubal ectopic pregnancy and adenomatoid tumor. The first case is presented of coexistance of an ectopic pregnancy and an adenomatoid tumor in the same fallopian tube. The ectopic pregnancy was diagnosed clinically, but the tumor was only detected microscopically as a result of extensive sampling of the salpingectomy specimen.


Active-site-directed alkylation of chymotrypsin by reagents utilizing various departing groups. Affinity-labeling reagents are useful for the inactivation of proteases in vivo but are apparently limited in application by the possibility of side reactions. In addition, increased specificity would be desirable. Substrate-derived chloromethyl ketones, one class of protease inhibitors, have been examined with the hope that replacement of the departing group halogen by other substituents might lead to improved inhibitor characteristics. Analogues of Z-Phe-Ch2X were synthesized in which X is a sulfonate or carboxylate substituent and examined as inactivators of chymotrypsin. The sulfonate esters were found to be more reactive than the previously studied halogen derivatives.


Synthesis of biologically active retroenantiomers of angiotensin peptides. The effect of the reversal of the direction of amide bonds in the peptide chain of angiotensin was determined by the synthesis and study of retroenantiomers of the following peptides: 1 [Val5]angiotensin II (angiotensin); 2, [Suc1]angiotensin (desamino-angiotensin); 3, [Ala7]desamino-angiotensin; 4, [beta-Ala7]desamino-angiotensin. In all of these retroenantiomers, the N-terminal Phe residue was replaced by a benzylmalonyl moiety in order to maintain the topological features of angiotensin's C terminus which are important for biological activity. The separation of the diasteromeric peptides containing D- or L-benzylmalonyl residues was possible in the cases of the retroenantiomers of 1 and 2 but not in those of 3 and 4. The retroenantiomers of 1 and 2 were devoid of smooth muscle contracting activities, while those of 3 and 4 contracted the isolated guinea-pig ileum and rat uterus with activities ranging from 8 to 24%, when compared with the respective parent compounds. The results indicate that (a) the sense of the peptide bonds in angiotensin's backbone is not essential for activity, and (b) the Pro7 residue in angiotensin is important for maintaining an "active" conformation of the molecule. The compounds reported in this paper are the first retroenantiomers of linear peptide hormones that have been shown to retain the biological activities of the parent compounds.


Use of cluster analysis in the development of structure-activity relations for antitumor triazenes. A series of antitumor triazenes in which the members of the series are physicochemically distinct was designed using the cluster analysis approach as proposed by Hansch and his co-workers. The series that resulted was tested against Sarcoma 180 in the mouse and the antitumor activities were analyzed using regression techniques. The structure-activity relations that resulted are discussed in terms of proposed mechanisms of action.


Potential central nervous system antitumor agents. Aziridinylbenzoquinones. A series of 15 2,5-diaziridinyl-3,6-bis(alkylamino)-1,4-benzoquinone derivatives was synthesized and evaluated as central nervous system antitumor agents in the murine intracerebral L1210 and ependymoblastoma brain tumor systems. Intraperitoneal activity was evaluted in the leukemia L1210, P388, and B16 melanocarcinoma tumor models. The more hydrophilic hydroxyalkylamino compounds were the most effective in the intraperitoneal ascites systems (L1210, P388) with the dihydroxypropylamino (18) and hydroxyethylamino (17) analogues producing long-term survivors. The simple, more lipophilic mono- and dialkylamino derivatives were most effective in the intracerebral systems. Multiple long-term survivors were obtained with the methyl (13), ethyl (14), and dimethylamino (20) compounds in the ependymoblastoma brain tumor system. The parent amino analogue 12 was very active in several tumor models. The relationship between structure, activity, and water solubility are discussed.


Stereochemical studies on medicinal agents. 21. Investigation of the role of conformational factors in the action of diphenylpropylamines. Synthesis and analgetic potency of 5-methylmethadone diastereomers. The synthesis of racemic threo- and erythro-5-methylmethadone (3a and 3b, respectively) was carried out and the solution conformation of each isomer was investigated through pKa and NMR studies. The data indicate that 3a-HCl exists exclusively in an internally hydrogen-bonded conformation while the erythro isomer 3b-HCl is present as a mixture of conformations. The erythro racemate 3b was found to possess 5.4 times the analgetic potency of (+/-)-methadone in contrast to the threo racemate 3a which was inactive and devoid of antagonist activity. The fact that the inactive racemate 3a contains the 5S,6R stereoisomer, which combines the configurations found in the more active enantiomers of methadone and isomethadone, suggests that the chiral centers do not behave as independent units and that conformational factors are playing an important role in governing stereoselectivity. These results, when analyzed together with earlier reports, suggest that one of the pharmacophoric conformations of the diphenylpropylamine analgetics possesses an antiperiplanar-like disposition of the Ph2CCOEt and +NHMe2 groups.


Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. Synthesis of 1'-methyl-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (7a, HP 365) and the demethyl analogue 9a (HP 505) was prompted by recognition of an aminoalkyl(aryl)isobenzofuran moiety common to the antidepressants talopram (Lu 3-010) and trans-10,11-dihydro-5,10-epoxy-5-[3-(methylamino)propyl]-5H-dibenzo[a,d]cyclohepten-11-ol (MK-940). Convenient laboratory synthesis of 7a was provided by lithiation of 2-bromobenzhydryl methyl ether, followed by addition of 1-methyl-4-piperidone and acid-catalyzed cyclization. N-Dealkylation by standard methods afforded 9a. Synthesis of analogues was stimulated by discovery of marked inhibition of tetrabenazine-induced ptosis for lead compounds 7a and 9a. Optimal antitetrabenazine activity is associated with the 3-phenylspiro-[isobenzofuran-1(3H),4'-piperidine] moiety where nitrogen is basic. Modification of this moiety by introduction of large nitrogen substituents or a C-3 substituent greater than H significantly reduced antitetrabenazine activity. A series of analogues with aromatic substituents was investigated; however, few of these compounds were significantly more active than 7a and 9a. Compound 9a was selected for additional studies.


Lipid solubility and affinity for N-demethylation of dansylamides in isolated rat hepatocytes. Isolated hepatocytes carry out the N-demethylation of dansylamide at near linear rates for up to 8 h. This reaction was measured by following the release of tritium into water on hydroxylation of 3H-labeled methyl groups. The competitive inhibition of dansylamide by dansylated amino acids was studied in this system as an example of competing drug metabolism in a series of compounds which are identical around the site of metabolism and different remote to that site. A correlation between lipid solubility and the Ki was not found over the entire range of substrate analogues. While most of the high Km inhibitors seem to correlate with lipid solubility, the highly lipophilic derivatives of the leucines and phenylalanine are in a separate group. Lipid solubilities of the dansylated amino acids were little affected by changes in pH and thus behaved as "essential nonelectrolytes".


Hashish. Unsaturated side-chain analogues of delta8-tetrahydrocannabinol with potent biological activity. Two delta8-THC derivatives, 4a and 4b, with functionalized side chains were synthesized. Treatment of (+)-trans-p-mentha-2,8-dien-1-ol with the resorcinal 2b followed by removal of the dithiol group with HgO--BF3-Et2O gave the aldehyde 3b. A Wittig reaction of dimethyl (2-oxoheptyl)phosphate with 3b furnished 4a, which was reduced to 4b. Compounds 4a and 4b showed potent cannabinoid-like activity in mice.


Potential bioreductive alkylating agents. 7. Antitumor effects of phenyl-substituted 2-chloromethyl-3-phenyl-1,4-naphthoquinones. Functional groups such as nitro, chloro, bromo, and methoxy were introduced in the meta and para positions of the phenyl ring of the antineoplastic agent 2-chloromethyl-3-phenyl-1,4-naphthoquinone. Tests for tumor-inhibitory potency of these derivatives against Sarcoma 180 ascites cells in mice indicated that the para-substituted methoxyphenyl, chlorophenyl, and bromophenyl derivatives possessed antitumor activity comparable to that of the parent compound 2-chloromethyl-3-phenyl-1,4-naphthoquinone, whereas meta-substituted nitro and bromo derivatives were either inactive or only weakly active anticancer agents in this system.


Preparation and antitumor activities of some derivatives of 5-methoxysterigmatocystin. A series of derivatives of 5-methoxysterigmatocystin (3a,12c-dihydro-8-hydroxy-6,11-dimethoxy-7H-furol[3',2':4,5]furo[2,3-c]xanthen-7-one) has been prepared and evaluated for antitumor activity. The potency of the parent compound has been associated with the intact bisfurano ring system and with the double bond in the terminal furan ring. It has been shown that new substituents can be introduced in the xanthone portion of the molecule and that the antitumor activity is in some cases preserved.


Synthesis and biological activity of 3,5-dinitro-4- and -2-(1H-purin-6-ylthio)benzoates, prodrugs of 6-mercaptopurine. A series fo prodrug modifications of 6-mercaptopurine (6-MP) containing dinitrobenzoate ester moieties with varying chain length has been prepared. These compounds were shown to be cytotoxic in several cell culture screens and also exhibited significant activity against L1210 lymphoid leukemia in vivo. The possibility exists that the transport and distribution of these compounds in vivo will be determined, in part, by increased lipophilic character, with a consequent selective localization in lymphatic and CNS tissue.


Synthesis and antihypertensive activity of some imidazoindole derivatives. The synthesis of pyridino[1,2-a]imidazo[5,4-b]indole (1) and thiazolo[3,2-a-a]imidazo[5,4-b-a]indole (2) has been achieved by phosphite reduction of 3-nitroso-6-phenylimidazo[1,2-a]pyridine and 5-nitroso-6-phenylimidazo[2,1-bb]thiazole. Compound 1 has shown strong antihypertensive activity in spontaneously hypertensive rats while compound 2 showed similar bioactivity both in spontaneously hypertensive rats and in normotensive dogs. A tricyclic amino derivative, 3-amino-2-phenylimidazo[1,2-a]pyridine, which has structural resemblance to compound 1, showed no hypotensive activity.


Studies in the design of x-ray contrast agents. Synthesis, hydrophobicity, and solubility of some iodoresorcyl bis(beta-glucosides). Two diiodo- and two triiodoresorcyl bis(beta-glucosides) were prepared and their hydrophobicity (log P octano) and water solubility were compared to a triiodophenyl beta-glucoside and several experimental nonionic, water-soluble, x-ray contrast agents. The data indicate steric overlap of the halogen substituents by the bulky hydrophilic O-beta-glucosyl substituents; high water solubility is attained only at observed log P octanol approximately 1.5 or lower. Of the new compounds, only 2,4,-6-triiodo-5-N-methylcarboxamidorescorcy bis(beta-glucoside) (6) was highly water soluble. At the physiological pHin dog's plasmia in vitro, compound 6 rapidly hydrolyzed. Poorly water-soluble but more stable compounds of this series were not appreciably absorbed from dog's duodenum.


Iodine-containing organic carbonates as investigative radiopaque compounds. Carbonates containing an iodinated aromatic ring on one side of the carbonate linkage and an alkyl group on the other were prepared. The aromatic side consisted of p-iodophenyl, p-iodobenzyl, m-iodobenzyl, 3,5-diiodobenzyl, m-amino-2,4,6-triiodobenzyl, m-acetamido-2,4,6-triiodobenzyl, p-iodophenethyl, p-iodo-sec-phenethyl, 3-(p-iodophenyl)propyl, 3-(p-iodophenyl)butyl, 2-(p-iodobenzyl)butyl, and 2-(iodobenzyl)hexyl groups. The alkyl portion of the carbonates was derived from alkyl alcohols containing from two to ten carbon atoms. The approximate lethal dose of intraperitoneal injections ranged from less than 1 ml/kg to more than 15 ml/kg. An investigation into the use of these compounds as radiopaques for myelography, lymphography, bronchography, and salpingography is underway.


Pyridoxal phosphate. 5. 2-Formylethynylphosphonic acid and 2-formylethylphosphonic acid, potent inhibitors of pyridoxal phosphate binding and probes of enzyme topography. The title compounds (17 and 21) were prepared in good yield by synthesis of the phosphonate diester acetals (14 and 19), deesterification with chloro- or bromotrimethylsilane, hydrolysis of the acetal group, and formation of the characterized barium salts. The 3-carbon aldehydrophosphonic acids (17 and 21) were potent inhibitors (Ki = 2 X 10(-6)) of pyridoxal phosphate (PPal) binding to apoaspartate aminotransferase (AAT) and are believed to span between and bind to the enzymic functional groups which bind the aldehyde and phosphate groups of PPal.


Quinazolines and 1,4-benzodiazepines. 75. 7-Hydroxyaminobenzodiazepines and derivatives. 7-Nitro-substituted benzodiazepines were reduced with stannous chloride in a buffered system to the corresponding 7-hydroxyamino derivatives. These compounds were alkylated, acylated, and converted to nitroso and azoxy derivatives. The rearrangement of a hydroxyamine to an aminophenol and its oxidation to an aminoquinone are also exemplified. The results of the pharmacological screening for CNS effects are given.


Trichothecene analogues. 1. 1,5-Dioxaspiro(2.5)octanes. Seven 1,5-dioxaspiro[2.5]octanes were synthesized and tested in the mouse P388 lymphocytic leukemia screen and the mouse Ehrlich ascites screen. These compounds possess the "epoxypyran" structure which has been believed to be the active portion of the trichothecene class of sesquiterpene tumor inhibitors. Three of the compounds were found to have marginal to moderate activity in the Ehrlich ascites screen (inhibition 74.1-86.3%) and low activity in the P388 screen (T/C = 126-131). A carbocyclic analogue, 1-oxaspiro[2.5]octane (9), was moderately active in both screens (inhibition 78.8%, T/C = 140). In the Ehrlich ascites screen, T-2 toxin (2) was about 25 times more potent than 9. None of the spirooctanes studied caused any skin irritation in 10-mg doses on the skin of rabbits, whereas 2 caused extensive necrosis at 0.1-mg doses.


Potential antitumor agents. 20. Structure-activity-site relationships for the 4'(9-acridinylamino)alkanesulfonanilides. A series of 87 L1210 active 4'-(9-acridinylamino)alkanesulfonanilides has been screened against L1210 cells (10(5)) implanted at various sites (ip, sc, ic) employing early ip drug administration for a limited time. With each implantation site a different most active congener was selected. For good activity against tumor implanted remotely from the ip drug administration site, an agent should be more lipophilic than that found optimal for ip implanted tumor. An acridine 4-CH3 group appears to assist drug translocation, possibly by sterically hindering binding to nonproductive sites. An unprotected NH2 group on the acridine ring system is incompatible with activity against sc implanted tumor. Agents in which NH2 is shielded by N-acetylation, N-monomethylation, or ortho substitution with a bulky group can inhibit sc implanted tumor.


Potential antitumor agents. 18. Bisquaternary ammonium heterocycles. It was earlier proposed that a close approach to overall planarity was a structural prerequisite for antileukemic activity (L1210) in bisquaternary ammonium heterocycles. The preparation of L1210 active 3,3'-[bicyclo[2.2.2]octane-1,4-dicarbonylbis(mino-p-phenylenecarbonylimino)bis(1-alkylpyridinium) salts, containing a nonplanar bridged ring system, negates this view. A replacement proposal is that a relatively rigid molecular framework in necessary to maintain the spacing and positioning of the quaternary functions, thereby ensuring correct site selection. Replacement of a terephthaloyl drug component by a bicyclo[2.2.2]octane-1,4-dicarbonyl residue lowers DNA binding. A terephthaloyl unit confers necessary molecular rigidity, greater DNA binding, and higher L1210 activity.


Para-substituted N-acetyl-L(S)- and -D(R)-alpha-amino-N-phenylglutarimides. A structure-activity study of substituent effects on steroselective anticonvulsant activity. For purposes of carrying out structure-activity studies on a series of pure R and S enantiomorphs of various para-substituted N-acetyl-alpha-amino-N-phenylglutarimides, we synthesized the p-acetyl, iodo, cyano, ethyl, and n-butyl analogues. These compounds complimented previous R and S isomers (unsubstituted and the p-chloro, methyl, nitro, and methoxyl analogues) synthesized in our laboratories from amino acids of known absolute configuration. The neurotoxic doses (TD50's), anticonvulsant potencies [maximal electroshock seizures (MES) and subcutaneous metrazole (sc Met) ED50's], protective indices (PI = TD50/ED50), and effects on minimal seizure threshold (iv Met) were compared with similar values concomitantly determined for clinically employed anticonvulsants. A parallel relationship was shown between neutotoxicity (TD50) and potency (ED50) for the R and S analogues. In most cases R isomers had a more rapid onset of action and possessed greater neurotoxicity and greater anticonvulsant potency.


Medical practice: defendants and prisoners. It is argued in this paper that a doctor cannot serve two masters. The work of the prison medical officer is examined and it is shown that his dual allegiance to the state and to those individuals who are under his care results in activities which largely favour the former. The World Health Organisation prescribes a system of health ethics which indicates, in qualitative terms, the responsibility of each state for health provisions. In contrast, the World Medical Association acts as both promulgator and guardian of a code of medical ethics which determines the responsibilities of the doctor to his patient. In the historical sense medical practitioners have always emphasized the sanctity of the relationship with their patients and the doctor's role as an expert witness is shown to have centered around this bond. The development of medical services in prisons has focused more on the partnership between doctor and institution. Imprisonment in itself could be seen as prejudicial to health as are disciplinary methods which are more obviously detrimental. The involvement of medical practitioners in such procedures is discussed in the light of their role as the prisoner's personal physician.


The place of medicine in the American prison: ethical issues in the treatment of offenders. In Britain doctors and others concerned with the treatment of offenders in prison may consult the Butler Report (see Focus, pp 157) and specialist journals, but these sources are concerned with the system in Britain only. In America the situation is different, both in organization and in certain attitudes. Dr Peter L Sissons has therefore provided a companion article to that of Dr Paul Bowden (page 163) describing the various medical issues in prisons. The main difference between the treatment of offenders in prisons in America and in Britain lies in the nature of the federal system which means that each state may operate a different system in a variety of prisons and prison medical services are as various. Nationally, the prison systems are 'structured to treat and cure the offender'. Therefore it follows that the prison medical officer is only one of the professionals concerned with this 'cure' of the offender. This principle also applies to any form of research: medical research in prisons is part of a programme which covers a wide field of social and judicial research. The prison medical officer (where there is one) has of course to look after sick prisoners, and the American idea of 'cure' is also expressed in the need for more corrective surgery where, for example, it is necessary to remove physical impediments to social rehabilitation. But a doctor is only found on the staff of those institutions which are large: in the smaller prisons there may be only first-aid facilities, and no specially appointed doctor in the community. Moreover medicines are often dispensed by medical auxiliaries who are sometimes prisoners themselves. Finally, in America prisoners are regularly invited to volunteer as subjects for medical and social research for which they are paid. In short, although it is hoped to 'cure' a prisoner he is a criminal first and a patient second.