The effects of splanchnic nerve stimulation on the plasma levels of serotonin and substance P in the portal vein of the cat.

The blood levels of serotonin (5-HT) and substance P (SP) in the portal vein were studied after splanchnic nerve stimulation in the cat. The portal levels of both substances were studied before, during and after splanchnic nerve stimulation. There was a twofold increase in 5-HT during stimulation whilst the SP concentration remained unchanged. These results suggest that the nervous control of the amine release into the portal stream and the mechanism that regulates the release of the polypeptide is not the same.


Age-related changes in catecholamine metabolites of human urine from birth to adulthood.

Catecholamines (dopamine [DA], norepinephrine [NE], epinephrine [E]), methoxyamines (3-methoxytyramine [MT], normetanephrine [NMN], metanephrine [MN]), DOPA, and acidic metabolites (3,4-dihydroxyphenylacetic acid [DOPAC], vanilmandelic acid [VMA]) were determined in human urines from one day of age to adulthood, in order to investigate sympatho-adrenal development during life. All adrenergic compounds are present in neonate urines on the first day of life, but their postnatal evolution is quite different according to the nature of metabolites. Daily E, MN and VMA amounts remain low until the 10th month of life; daily NE, MT and DOPA levels increase progressively, but, in contrast, NMN amounts are already high in the neonatal period and increase only beyond the fourth year of age. DA is at either age the predominant catecholamine but its elimination is relatively more important in the neonatal period.


Clozapine induced increase of human plasma norepinephrine.

Four psychotic patients and 5 controls were treated with clozapine (200--400 mg/day during 30 days, patients, respectively 100 mg/day during 7 days, controls) and plasma norepinephrine (NE) concentration was measured. In the morning, shortly after end of sleep, plasma NE concentration was significantly increased under clozapine treatment in both populations. The effects of clozapine were explained with a direct pharmacological action of the drug on NE receptors.


The intra-axonal transport of acetylcholine and cholinergic enzymes in rat sciatic nerve during regeneration after various types of axonal trauma.

The proximo-distal intra-axonal transport of acetylcholine (ACh) and cholinergic enzymes (choline acetyltransferase, CAT, and ACh-esterase, AChE) in rat regenerating sciatic nerve was studied by accumulation technique. Four types of axonal trauma were performed: freezing with solid CO2, crushing, ligating the nerve with remaining tight silk ligature, and cutting the nerve. Normal and sham-operated rats were used as controls. One to twenty-nine days later, the nerves were crushed about 15 mm proximal to the trauma. The nerve segment proximal to this crush was dissected out 12 hr later and assayed for ACh-content and enzyme activities. The increase in this segment 12 hr after crushing was taken as an indication of proximo-distal transport in the regenerating nerves. ACh transport did not seem to vary during regeneration as compared to controls. In contrast, the transport of both CAT and AChE was initially markedly depressed. Towards the end of the observation period (29 days), a recovery of CAT-transport occurred in all groups. Recovery of AChE-transport was marked in the freeze and crush groups. In the cut group no recovery was seen and in the ligated group only a small recovery occurred. Thus, in the nerves where regeneration was facilitated by the presence of intact connective tissue sheaths (freezing and crushing) recovery of transport occurred earlier than in cut or ligated nerves.


Motor innervation of the pharynx levator muscle of the snail, Helix pomatia: physiological and histological properties.

(1) Motor innervation of the pharynx levator muscle of Helix pomatia was investigated with intracellular recording and axonal iontophoresis of cobalt chloride. (2) Muscle fibers respond to direct electrical stimulation of the muscle with active graded responses or non-overshooting spike potentials. (3) Each fiber is innervated via the external and internal lip nerves by several (mostly 3) excitatory nerve fibers each. Two types of EPSPs can be distinguished according to amplitude, duration, and facilitation. (4) Axonal CoCl2-staining via an external lip nerve branch revealed many nerve fibers entering the muscle and branching there into a rich network of blebbed fibers of various diameters.


The structure and function of serially homologous leg motor neurons in the locust. II. Physiology.

Simultaneous intracellular recordings were made from pairs of motor neurons in the pro- or mesothoracic ganglion of the locust. Though central connections were sought between pairs of motor neurons, none were found. This is in sharp contrast to the findings that flexor and extensor tibiae neurons in the metathoracic ganglion make certain connections between themselves (Hoyle and Burrows, 1973; Heitler and Burrows, 1977a). As the previously mentioned authors believed that the metathoracic flexor-extensor connections were used as part of the motor program for jumping and kicking, the present results strongly support their hypothesis. Common PSPs have been found in a variety of pairs of motor neurons. Of note are common PSPs of the same sign to antagonists. Different innervation patterns have been found for the flexor and extensor muscles. It is proposed that serially homologous motor neurons serving similar functions are, to a first approximation, similar in the locust. Serially homologous motor neurons serving different functions will, in most cases, have altered structures and/or functions.


Autophosphorylation of chick brain synaptic polypeptides. Phosphorylation of proteins during incubation of intact synaptosomes with 32PO4.

Chick brain synaptosomes incorporated phosphate into proteins when incubated in physiological buffer containing energy sources. Sodium dodecyl sulfate polyacrylamide gel electrophoresis indicated that three synaptosomal polypeptides were significantly phosphorylated after 15 sec incubation while at least fifteen polypeptides were active kinase substrates after 15 min incubation. Labeled synaptosomes were hypotonically lysed and separated by centrifugation into soluble, membrane, and mitochondrial fractions. Every fraction exhibited significant phosphate incorporation. Electrophoresis revealed that each fraction had several unique phosphorylated polypeptides and a distinctive phosphorylation pattern. The same polypeptides appear to be labeled whether MgATP was added to synaptic plasma membranes or synaptic plasma membranes were isolated after synaptosomal autophosphorylation.


Retrograde axonal transport of specific macromolecules as a tool for characterizing nerve terminal membranes.

The uptake of macromolecules by nerve terminals which is followed by retrograde axonal transport seems to occur by two different mechanisms, a specific and a nonspecific one. The nonspecific uptake depends on the presence of macromolecules (e.g., horseradish peroxidase) in the vicinity of the nerve terminals at very high concentrations and is enhanced by neuronal activity. In contrast, the specific uptake and subsequent retrograde axonal transport becomes apparent at much lower concentrations of the appropriate macromolecules, depends on the affinity of these ligands for specific binding sites on the surface of the neuronal membrane, and is independent of neuronal activity. The fact that lectins and some bacterial toxins bind to specific membrane glycoproteins or glycolipids allows conclusions to be drawn regarding qualitative and even quantitative aspects of the composition of the plasma membrane of the nerve terminals. 125I-labelled nerve growth factor (NGF), tetanus toxin, cholera toxin, wheat germ agglutinin (WGA), ricin II, phytohemagglutinin (PHA), and concanavalin A (ConA) were injected into the anterior eye chamber of rats where they were taken up by adrenergic nerve terminals and transported retrogradely to the superior cervical ganglion. The saturation of the uptake-transport found for NGF, WGA, choleragenoid and an atoxic binding-fragment of tetanus toxin indicates that limited numbers of binding sites, which showed also different affinities, are present for each ligand on the membrane of the nerve terminals. Competition experiments showed that the binding sites for the ligands investigated are largely independent. Two different classes of binding sites (high affinity--low capacity and intermediate affinity--intermediate capacity) seem to be involved in the saturable retrograde axonal transport of NGF. In contrast, WGA seems to have only a single class of binding-uptake sites with high capacity and relatively low affinity. Strong evidence for positive cooperativity was obtained for the uptake and subsequent transport of the tetanus toxin fragment.


Reduction of methemerythrin-anion adducts by dithionite ion.

The reduction by dithionite ion (in excess) of methemerythrin-anion adducts, Hr+X-, to deoxyhemerythrin, Hr degree, has been examined at 25 degrees and pH 6.3 and 8.2. The results accord with the scheme: S2O42- in equilibrium 2SO2- rapid Hr+X- in equilibrium Hr++X- k-1, k1 Hr++SO2- leads to PRODUCT k2 with X- = Br-, HCO2-, CNO-, and F-, k2[SO2-] greater than k1[X-], and the pseudo first-order rate constant, kobs (= k-1), is independent of [X-] and [S2O42-]. Only with X- = NCS- is k2[SO2-] approximately k1[X-] and kobs = a[S2O42-]1/2 (b[NCS-] + [S2OR2-]1/2)-1. Values at pH 6.3 of k-1 (sec-1) and k1 (M-1 sec-1), obtained by anation and anion displacement reactions, are 2.3 x 10(-3), 1.6 x 10(-2) (Br-); 1.5 x 10(-3), 1.2 x 10(-2) (HCO2-); 1.3 x 10(-4), 0.52 (CNO-) and approximately 2 x 10(-4), 3.3 x 10(-3) (CN-, pH 7.0). Values of k-1 from reduction and displacement methods are in good agreement with each other. The value of k2 (1.6 x 10(5) M-1 sec-1, pH 6.3) in somewhat smaller than that for reduction of the met form of hemoproteins. There is only a small effect of pH on rates. Direct reduction of Hr+CN- does not occur, in contrast with Mb+CN-.


Biologically related iron-sulfur clusters as reaction centers. Reduction of acetylene to ethylene in systems based on [Fe4S4(SR)4]3-.

The possibility that clusters containing the Fe4S4 core unit found in a wide variety of proteins can effect reductive transformations of Fe-S enzyme substrates has been investigated using the reduced synthetic clusters [Fe4S4(SPh)4]3- and acetylene, an alternate nitrogenase substrate. The system [Fe4S4(SPh)4]3-/acetic acid/acetic anhydride in N-methylpyrollidinone at approximately 25 degrees was found to reduce acetylene homogeneously to ethylene, and in the presence of a deuterium source to afford as the principal stereochemical product cis-1,2-C2H2D2. No appreciable reduction was found using the oxidized cluster [Fe4S4(SPh)4]2-. The system is not catalytic and departs from the strict stoichiometry of the reaction, 2[Fe4S4(SPh)4]3- + C2H2 + 2H+ leads to 2 [Fe4S4(SPh)4]2- + C2H4, primarily because of a competing cluster oxidation reaction which could not be eliminated. Based on this reaction ca. 60% conversion of acetylene to ethylene was achieved. A reaction sequence based on absorption and 1H nmr spectral observations and product stereo-chemistry is suggested. The results demonstrate that biologically related, reduced Fe4S4 clusters can effect reduction of at least one Fe-S enzyme substrate, and raise the general possibility of substrate transformation with such clusters as reaction sites in biological systems.


The formation and nature of the mixed valence copper-D-penicillamine-chloride cluster in aqueous solution and its relevance to the treatment of Wilson's disease.

Complex formation between D-penicillamine (Pen) and copper(II) ions has been studied under simulated physiological conditions in both the presence and absence of the blood plasma constituents albumin, alanine, histidine, and zinc(II). Chromatographic and uv/vis and electron spin resonance (esr) spectroscopic methods were used. The major species formed, at neutral pH and 0.15 mol dm-3 NaCl, is the violet species which is shown to have the same stoichiometry as the recently reported solid-state complex, i.e., [Cu8I Cu6II (Pen)12 Cl] 5-. The rate of formation of this species (MVC) is shown to be dependent on the Cu concentration, Cu:Pen ratio, relative Cl- ion concentration, pH, and temperature. Formation is inhibited by the presence of O2 and biological chelates. At the concentration levels found in blood plasma it is unlikely that the MVC ion has any significance in the therapeutic action of penicillamine in the treatment of Wilson's disease. Reexamination of the aqueous Cu-albumin-pen system reinforces earlier findings that pen is unable to mobilize Cu that is bound to albumin. Significant binding of pen to the protein is observed is not related to any protein-bound copper ions. Evidence that ternary complexes of the type amino acid-Cu-Pen can form in blood plasma is presented. These are unlikely, however, to be physiologically significant and the copper depletion induced by Pen in Wilson's disease cases must be elsewhere than in the blood plasma compartment.


Developmental patterns of copper and zinc concentrations in mouse liver and brain: evidence that the gene crinkled (cr) is associated with an abnormality in copper metabolism.

An abnormality in copper metabolism during both the prenatal and postnatal (preweaning) periods was found to be associated with the autosomal recessive gene "crinkled" (cr) in mice. Liver copper concentration was significantly lower in crinkled mice (cr/cr) than in littermate controls (+/?) from 18 days of gestation to 20 days after birth. Crinkled mice older than 20 days of age and liver copper concentrations similar to those of littermate controls. Liver zinc and brain copper and were similar in crinkled and noncrinkled mice at all times tested. In both crinkled and noncrinkled mice, brain copper concentration increased during the suckling period, and liver copper concentration decreased.


Sialidosis type 1: cherry red spot-myoclonus syndrome with sialidase deficiency and altered electrophoretic mobilities of some enzymes known to be glycoproteins. 1. Clinical findings.

A family is described with three affected brothers, two of whom were examined, born to consanguineous parent, who in early adult life began to experience ataxia, intention myoclonus, and progressive visual failure. The brothers examined had cherry red spots at the maculae and cataracts. They were of normal intelligence. The intention myoclonus responded partially to treatment with clonazepam and pheneturide, but not to 5-hydroxytryptophan in combination with carbidopa or to sodium valproate. Studies in one patient showed the excretion of large quantities of sialylated oligosaccharides in the urine. Both patients showed deficient sialidase activity in their cultured fibroblasts. Further studies on cultured skin fibroblasts revealed increased electrophoretic mobility of six glycoprotein enzymes that was returned approximately to normal by treatment with sialidase. The clinical and biochemical findings indicate that these patients are further cases of the newly described condition sialidosis type 1.


Abnormalities of cerebrospinal fluid amino-acids in purulent meningitis.

Serial measurements were made of the cerebrospinal fluid and plasma amino-acid concentrations in 12 patients with purulent meningitis. Marked increases in the concentrations of most CSF amino-acids were found, possibly caused by altered transport mechanisms in the inflamed meninges and choroid plexuses.


Amine metabolites in ventricular cerebrospinal fluid in coma.

The concentrations of homovanillic acid (HVA), 3-methoxy, 4-hydroxyphenylglycol (MHPG), and 5-hydroxyindolylacetic acid (5-HIAA) were measured in samples of ventricular cerebrospinal fluid (CSF) taken from 15 patients who were comatose as a result of an acute head injury, a tumour, or a cerebrovascular accident. The metabolite levels were not related to the ventricular fluid pressure. In the eight patients who recovered and from whom serial samples of CSF were obtained, the metabolite levels did not change, except for two patients in whom HVA increased as coma progressed. The concentration of MHPG, but not of HVA or 5-HIAA, was greater (P less than 0.02) in the five patients who died without regaining consciousness than in the 10 patients who recovered.


beta-Adrenoreceptor antagonists in essential tremor.

Three different beta-adrenoreceptor antagonists--propranolol, sotalol, and atenolol--were compared in a double-blind study with placebo in nine patients with essential tremor. All three drugs produced an equal reduction in standing pulse rate but atenolol was less effective in reducing tremor than propranolol and sotalol. These results suggest that the reduction in tremor produced by beta-adrenoreceptor antagonists is mediated by an effect on peripheral beta 2-adrenoreceptors.


Angina pectoris with normal coronary arteries in Shy-Drager syndrome.

A patient with Shy-Drager syndrome who presented with severe angina pectoris is described. Special investigations of his autonomic nervous system showed sympathetic and parasympathetic dysfunction with supersensitive end-organ response. Sympathetic dysfunction manifested as labile hypertension, severe postural hypotension, and inadequate heart rate response to atropine and the Valsalva manoeuvre. These changes in blood pressure were accompanied by severe disabling angina pectoris. Selective coronary angiography showed normal coronary arteries. It is suggested that angina pectoris resulted from the inadequate circulatory response and is another clinical manifestation of the Shy-Drager syndrome.


Infection of the brainstem by Listeria monocytogenes.

A case of brainstem infection by Listeria monocytogenes is described. The patient was a 63 year old man previously in good health and his illness did not follow the usual bi-phasic pattern. There was no prodromal phase, and the progressive brainstem signs with a lymphocytosis and a normal sugar level in the CSF led to a tentative diagnosis of viral brainstem encephalitis. Ampicillin was begun only when signs of pulmonary infection developed. Clinical diagnosis is difficult but ampicillin should probably be used in any doubtful case in which a "viral" brainstem encephalitis is being considered.


Multiple sclerosis plaque related to abnormal somatosensory evoked potentials.

A patient with mild multiple sclerosis died from a ruptured intracranial aneurysm. It was possible to relate abnormalities of somatosensory evoked potentials recorded some months earlier to a plaque involving the root entry zone in the cervical spinal cord which had not resulted in clinical sensory abnormalities.


Tonic vibration reflex in Holmes-Adie syndrome: an electrophysiological study.

The pathophysiological mechanisms underlying benign areflexia were studied in six patients with Holmes-Adie syndrome. No impairment of sensory conduction velocity of sural nerve was found. A normal tonic vibration reflex was obtained in all patients. H reflex was absent in five patients, but responses like F waves were recorded in three subjects. These findings suggest that muscle spindles are not affected and that spinal motoneurone excitability is normal.


Psychoses in drug-resistant temporal lobe epilepsy.

In the survey of 74 Danish patients with temporal lobe epilepsy who underwent temporal lobectomy, a total of 20 patients were psychotic. Nine of these became psychotic during the follow-up period, six of them after cessation of their epileptic seizures. There were 13 schizophrenia-like psychoses, six paranoid delusional and depressive psychoses, and one childhood psychosis. Operation was on the right side in 39 and on the left side in 35 patients. When the various psychotic groups were compared with each other or with the nonpsychotic patients, the side of operation was not found to be statistically important. The patients with psychoses were older at operation and showed a higher rate of focal lesions in the resected specimens. Although more psychotic patients were bright or normally gifted, and had achieved a higher standard of schooling than nonpsychotic patients, their social status after operation was inferior. Surgery had no effect on psychosis present preoperatively nor on its possible postoperative onset. The diagnosis of psychosis was not considered to be contraindication to temporal lobectomy.


Myonuclear calcium in carriers of Duchenne muscular dystrophy. An X-ray microanalysis study.

Electron-microscopic X-ray microanalysis (EMMA) was used to study calcium and phosphorus concentrations in the muscle fibre nuclei of 3 genetically definite, 5 probable and 2 possible carriers of Duchenne muscular dystrophy. All cases showed elevated mean calcium:phosphorus ratios compared with 4 female controls and, with the exception of one possible carrier, all showed elevated calcium concentrations. A significantly greater variation of values was also found for both parameters. Analyses were made of nuclei from fibres showing no morphological abnormalities and the results suggest elevation of myonuclear calcium may be an early defect in dystrophic muscle.


Trophic muscle regulation in children with congenital cerebral lesions.

A decrease in sarcomere number and hypoextensibility of ankle extensors was observed in certain children with congenital cerebral lesions. This phenomenon was reproducible and reversible in normal animals, i.e. trophic regulation adapted the muscle to the imposed length. The form of the torque-ankle angle curve was studied in 30 children. Its modification after treatment was considered as a sign of muscle adaptation. This adaptation was present in one group of 14 children. The steepness of the curve increased or diminished depending on the initial disorder and the treatment administered. In another group, treatment failed to modify the shape of the curve. In certain cases trophic regulation of the muscle appeared to be absent.


Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus.

A morphologic study of demyelination produced by Theiler's encephalomyelitis virus (TMEV) infection in C3H/He mice was performed. Demyelination in this strain of mouse was less intense and had a milder gliomesodermal response than that observed in SJL mice. As early as 80 days after infection numerous remyelinated axons were present in C3H/He mice, and later, extensive remyelination was observed and was mainly by Schwann cells. About one-third of remyelinated plaques showed recurrent demyelinating activity at 200 days. The best evidence of recurrent demyelination was the loss of myelin by abons which had been previously remyelinated by Schwann cells. In addition, acute areas of demyelination were also seen in spinal cords which contained chronic or quiescent plaques. The demonstration of recurrent demyelination in TMEV infection is important for it increases the relevance of this model to multiple sclerosis (MS). In addition TMEV infection of C3H/He mice appears to be an excellent model for further studies of Schwann cell remyelination and recurrent demyelination in the central nervous system (CNS).


Topographical distribution of arsenic, manganese, and selenium in the normal human brain.

The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brain from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron activation analysis with radiochemical separation. Distinct patterns of distribution were shown for each of the 3 elements. Variations between individuals were found for some but not all brain areas, resulting in coefficients of variation between individuals of about 30% for arsenic, 10% for manganese and 20% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue.


[Cerebral manifestations in angioneurotic edema (author's transl)].

Two patients with hereditary angioneurotic edema are described. A female patient, born in 1929, showed an infarction in the area of the right posterior cerebral artery, verified by computer tomography. The son of this patient, aged 20 years, suffered from a transitory ischemic attack and a prolonged reversible ischemic neurological deficit, both in the territory of the left middle cerebral artery. Etiology, symptomatology, therapy, and differential diagnosis of cerebral manifestations in angioneurotic edema are discussed in view of previously described cases.


Thyrotoxic myopathy: a clinical and quantitative analytic electromyographic study.

The clinical entity of chronic thyrotoxic myopathy was considered rare by Waldenström in 1945. Forty eight consecutive patients with thyrotoxicosis were studied clinically and by electromyography for muscle involvement. Quantitative electromyographic techniques were used to analyse both the electromyographic activity of the muscle at a standard tension and also the single motor potential obtained in isolation at minimal effort. The interference pattern was described in simple numerical terms such as the number of potential changes/s and the mean amplitude. All cases that were thyrotoxic (both clinically and on thyroid function tests) showed the changes of myopathy on electromyography, though only 68% of the cases showed clinical myopathy consisting of muscle weakness and/or atrophy.


Neuropathy in tetanus.

Thirty-four cases of severe tetanus were studied. On clinical examination weakness and sensory loss compatible with peripheral neuropathy was found in 27. The pattern was usually asymmetrical, the commonest nerves affected being ulnar, median and lateral popliteal, although occasionally circumflex, musculocutaneous, femoral and facial nerves were also involved. Electrophysiological studies showed spontaneous activity resembling denervation potentials, diphasic and positive sharp waves. In some muscles there was also activity resembling spontaneous firing of motor units. Motor and sensory conduction velocities in the affected nerves were moderately reduced and the amplitude of sensory potentials was also reduced. No conduction was found in 11 nerves in 8 patients on initial studies, but 4 out of 7 nerves that could be studied showed rapid recovery. Although most of the nerves in the rest of the patients showed clinical recovery, conduction velocities showed improvement most often when examined about 10 weeks after the onset of trismus. The clinical and electrophysiological evidence suggests the involvement of peripheral nerves in severe tetanus. Serum neuritis, hypersensitivity reaction to tetanus toxoid or drug-induced neuropathy have been ruled out.


Distal spinal muscular atrophy. A clinical and genetic study of 8 kindreds.

Twelve patients (8 kindreds) with distal SMA are described, and an analysis presented of their clinical and genetic features. Distal SMA accounted for 10% of all patients with SMA in a total population survey of this disease in North-East England. The parental consanguinity rate is high, occurring in 3 of the 8 kindreds reported; the sex ratio was 1.0; the segregation ratio of sibs did not differ from 0.25. Intrafamilial concordance for clinical features of the disease is high. This current data is consistent with a suggested aetiology of two separate autosomal recessive genes. Clinical features are discussed and a review of the literature presented. The disease is only slowly progressive, but one of the genetic types may present with infantile or early juvenile onset; there is no evidence that it shortens life. 50% of cases did not have a normal gait after 4 years of age; 50% could not run after 17 years of age; and 50% could not walk unaided after 28 years of age. Details of prognosis, and principles of genetic counselling in this disease are discussed.


Gliogenesis and ependymogenesis during embryonic development of the rat. An autoradiographic study.

With the aid of [3H]thymidine autoradiography gliogenesis and ependymogenesis were studied in the brain of the rat during embryonic development. Gliogenesis was found to begin on day 17 of gestation in the caudal regions of the brain stem, and to spread rostrally. On days 20 and 21 of gestation gliogenesis reached a peak, and then declined. Ependymogenesis began earlier and showed the following pattern: day 14 of gestation in the 4th ventricle and cerebral aqueduct, day 15 in the 3rd ventricle, and day 17 in the lateral ventricles reaching a peak on different days in different sites. Both gliogenesis and ependymogensis continued up to the last day of gestation, day 22. Issues pertaining to gliogenesis and the formation of glioblasts, and the relationship between gliogenesis and ependymogenesis are discussed.


Degenerative changes at the neuromuscular junctions of red, white and intermediate muscle fibers. Part 1. Response to short stump nerve section.

Degeneration at the neuromuscular function following cutting the phrenic nerve at the 9th intercostal space differs in red, white and intermediate skeletal muscle fibers. The ultrastructure of the nerve terminal and the muscle fiber between 12 hours and 21 days following denervation suggests that lack of neurotrophic influences results in responses specific for each fiber type. Degeneration of axon ends is rapid and by 2 days axon terminals are missing from the end-plate areas of all 3 fiber types. Schwann cells "engulf" degenerating axon terminals and eventually replace them in the primary clefts. Schwann cells display specific morphological changes directly related to axonal degeneration. In all instances axon terminal degeneration precedes muscle fiber degeneration. Synaptic cleft changes are similar for all types of muscle fibers. Primary cleft structure appears to be dependent upon neurotrophic influence, whereas secondary cleft structure is relatively unaffected by denervation. Initial changes in subsynpatic regions of muscle fibers include focal loss of sarcomere alignment and skewing of the Z lines. By 21 days myofibrillar disorganization appears most severe in white fibers and least in red muscle fibers. The rate and degree of degeneration of the axon terminal and subjacent muscle fiber are different for each of the 3 muscle fiber types.


Degenerative changes at the neuromuscular junctions of red, white, and intermediate muscle fibers. Part 2. Responses to long stump nerve section and colchicine treatment.

The ultrastructure at the neuromuscular junction (NMJ) of red, white, and intermediate skeletal muscle fibers undergoes specific changes following either unilateral severance of the phrenic nerve or unilateral topical treatment of the phrenic nerve with colchicine. Both procedures were performed in the cervical region and produce similar rates of muscle fiber degeneration. The severity of degeneration appears to be related to muscle fiber type with white fibers being most severely affected and red fibers least affected. Degeneration rates of the axon terminal also correlate with fiber type in the orderwhite, intermediate, red. However, the rates of degeneration of the specific axon terminals are more rapid with surgical severance than with colchicine treatment. Statistical analysis of morphometric data indicates that hemidiaphragms denervated surgically exhibited significant axon terminal degeneration before significant muscle degeneration. Conversely, diaphragmatic muscle fibers of colchicine-treated phrenic nerves exhibit significant degeneration before loss of the axon terminal. Despite reversal of the temporal sequences for loss of axonal and muscular components between the two preparations, degenerative characteristics of muscle fiber structure are similar. This suggests that the presence of fiber-specific neurotrophic substances transmitted from the neuronal cell body to the axon terminal and released at the NMJ may be an important factor in the maintenance of normal muscle fiber morphology.


The significance of the estimation of serum myoglobin in neuromuscular diseases.

The serum myoglobin concentration was determined and compared with the serum creatine kinase activity in 230 patients suffering from various neuromuscular diseases. No correlation was found between the two levels. In general serum creatine kinase activity estimation seemed more sensitive for the detection of neuromuscular disease than serum myoglobin estimation. In myotonic dystrophy, however, determination of serum myoglobin was distinctly the more sensitive method.


The effects of murine muscular dystrophy on the metabolic and homeostatic functions of the skeletal muscles.

The maintenance of blood glucose is largely dependent on the ability of the skeletal muscles to regulate the supply of amino acids for hepatic glucose production. This study shows that when muscles are damaged in muscular dystrophy the mechanisms by which this control is exerted are impaired. In normally fed congenitally dystrophic mice the blood glucose level was raised and there were significant reductions of the levels of the principal gluconeogenic amino acids in the circulation. This was a result of abnormal exchange of amino acids between the dystrophic muscles and the blood, apparently due to the use of amino acids to a considerable extent in place of glucose for energy metabolism within the diseased muscles. When dystrophic animals were fasted, further reductions in the levels of amino acids in the circulation, to abnormally low values, were caused by an increased use of these amino acids by the liver for gluconeogenesis. Although the reason for the excessive metabolism of amino acids in dystrophic muscle is not clear, such changes will favour muscle protein breakdown, and a stress such as fasting will further aggravate the process of muscle wasting by depleting still further the pool of amino acids in the body.


Noninvasive measurement of cerebral vasopasm in patients with subarachnoid hemorrhage.

Regional cerebral blood flow (rCBF) was measured as fast flow clearance (F1) and the initial slope index (ISI2) after inhalation of 133Xe in 30 patients with subarachnoid hemorrhage (SAH). Vasomotor responsiveness to reduction in end-tibal PECO2 was examined in those patients who could carry out this procedure satisfactorily as a test for the presence or absence of vasospasm. F1 and ISI2 were significantly reduced in patients with recent SAH compared to 35 age-matched normal volunteers. The degree of reduction of F1 and ISI2 correlated directly with severity of the neurological deficit graded according to the Hunt and Hess rating scale. Topographic reductions of rCBF correlated with angiographically demonstrated vasospasm or intracerebral hematoma. The degree of impairment of cerebral vasomotor responsiveness to reduction of PECO2 by hyperventilation also correlated with the severity of vasospasm demonstrated angiographically in 16 patients. The reductions of rCBF values were maximal during the first week after SAH but returned gradually toward normal by the 5th week. Individual patients with SAH whose lowest F1 values were above 50 ml/100 g brain/min tolerated surgical intervention best. Non-invasive measurements of rCBF after SAH appear to be helpful in estimating the presence and time course of vasospasm, in recognizing the development of normal pressure hydrocephalus, and in planning medical and surgical management.


Chronic form of childhood spinal muscular atrophy. Are the problems of its genetics really solved?

The authors discuss the differences between the two large series of chronic childhood spinal muscular atrophies (SMA)--their own comprising 273 cases, and that of Pearn et al. comprising 141 cases. The main difference concerns the predominance of males in the clinically milder later-onset group in the present series. The data of Pearn et al. (1978a, b) are quite different. The reason for the discrepancies is apparently a different selection of material. The present material is highly selective in favour of chronic cases, and Kugelberg-Welander cases are well-represented, whereas the percentage of Kugelberg-Welander cases in the material of Pearn et al. was very small. Differences in selection also appear to be responsible for discordance in observations regarding influence of sex on the course of the disease. The present data seem to support the view that most of the cases revealing chronic forms of SMA (both mild and severe) are not distinct genetically. However, the possible existence of a distinct subgroup in which sex influence is strongly expressed is not excluded.


Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord.

The anterior funiculus of the spinal cervical cord of post-natal rats was examined ultrastructurally. The myelinating cells found one day after brith contained a large amount of evenly distributed ribosomes up to the outer tongue of mesaxons, representing the cytoplasmic density. These cells were separated by astrocytic processes from the pial basement membrane, even when they were located on the pial surface. Astrocytes contained glial fibrils from one day onwards and often attached their processes to the pial basement membrane. Although the cytoplasmic processes of astrocytes occasionally wrapped axons, they were never shown to form the initial layer of myelin sheaths. However, the tenuous processes of the sub-pial astrocytes were occasionally rolled in myelin lamellae, as if a part of the myelin sheaths was constructed by astrocytic processes. The interpretation for this finding is discussed in relation to function and potency of the astrocytes, and variations and anomalies of nervous ontogeny.


The diagnostic value of spectrophotometric analysis of the cerebrospinal fluid in cerebral hematomas.

On a clinical basis it is sometimes impossible to distinguish between small intracerebral hematomas and reversible ischemic strokes (RIND). Analysis of the cerebrospinal fluid (CSF) has been used in ths context for several years and is still of importance even since the introduction of computerized tomography (CT) of the brain. CSF has been examined in 23 patients with intracerebral hematomas. Typical cell changes with an increase of poly- and mononuclear white cells are seen within the first days after the stroke, whereas clearly pathological spectrophotometric changes are not seen until about one week after the stroke. None of the investigated patients had a significant increase of the absorbance values at the wavelenths 406 and 415 nm (met- and oxyhemoglobin) until 5 days after the stroke.


Peripheral intraaxonal storage in Tay-Sachs' disease (GM2-gangliosidosis type 1.

Considerable intraaxonal lipid storage was observed in intramuscular nerve fibres mainly of the extraocular muscles and less frequently in limb muscles of a 3-year-old child, which had suffered from Tay-Sachs' disease. Many axons of the small intramuscular nerve twigs and of the terminal and preterminal nerve endings showed spherical and cylindrical enlargements containing granular storage material of the same staining properties  as the material in the central nervous system. The identify of the axonal and the neuronal storage material was further confirmed by electron-microscopical demonstration of typical multilamellated cytoplasmic bodies (MCBs) in both of them. In addition, silver impregnation and electron microscopy revealed dystrophic changes with an increase of argyrophilic filamentous material within some of the axonal distensions, indicating that the latter were probably due to both a lipid storage and an unspecific dystrophic process.


Abnormal leukocyte electrophoretic mobility in myotonic dystrophy.

Electrophoretic mobility of polymorphonuclear leukocytes (PMNs) was studied in 10 patients with myotonic dystrophy. The mobility of patients' PMNs differed significantly from that of controls. Following incubation with bacterial chemotactic factor the PMNs from patients showed significantly less change in net surface charge compared to that in controls. Our data support a leukocyte membrane defect in myotonic dystrophy.


Acute ischaemic neuropathy in the rabbit.

Ligation of either the common and internal iliac or the internal and external iliac arteries produced ischaemic lesions of the sciatic nerve and its branches, as well as direct muscle damage, in 5 out of 6 rabbits. In one animal, ligation of the aorta and of the internal iliac artery on one side produced a similar mixture of nerve and muscle damage on the side of the double ligation. Ligation of the femoral artery alone in 3 animals failed to produce significant changes. In the 6 affected animals there was paralysis of the hind leg on the side of the iliac ligations, with loss of tendon reflexes. Appreciation of pinprick over the foot and lower leg also appeared to be impaired. Complete ischaemic necrosis with irreversible damage to both neural and connective tissue elements did not occur in the main nerve trunks, but was present in some of the intramuscular nerve bundles as part of generalized coagulative necrosis of the most severely affected muscles. The characteristic pathological changes in the nerve fibres of the main nerve trunks were Wallerin degeneration and paranodal demyelination, the former being more extensive than the latter. In the animals with double iliac ligations, the upper level of ischaemic nerve damage was in the thigh, the tibial portion of the sciatic nerve being more commonly affected than the peroneal. Nerve and muscle damage tended to occur at different levels in the limb, but there was no example of clinical paresis due to neural damage without any ischaemic muscle changes being present. In two of the 3 animals in which the plantar muscles were examined, these muscles appeared to escape direct damage in spite of ischaemic lesions in the more proximal parts of the limb.


Lysophosphatidyl choline-induced focal demyelination in the rabbit corpus callosum. Light-microscopic observations.

The local application of lysophosphatidyl choline (LPC) by microinjection into the region of the corpus callosum of the rabbit produced demyelinating lesions. The lesions were assessed histologically using the Luxol fast blue myelin stain and the Holmes silver nitrate stain for the axis cylinders. Survival times for the animals ranged from 7 to 14 days. The center of the lesion was marked by infiltration of macrophages and necrosis, but the major area of the lesion was characterized by demyelination. By consideration of anatomical factors influencing LPC diffusion and of the appropriate placement of the injection, the entire vertical extent (about 0.5 mm) of the corpus callosum could be demyelinated with minimal amounts of necrosis. Since focal demyelination was possible in the fine caliber axons of the corpus callosum which are anatomically representative of many forebrain fiber systems, and since this fiber system is amenable to chronic physiological investigation, the corpus callosum may serve as an experimental model for morpho-physiological studies of mammalian central demyelinating pathways.


Cystic intracranial tumours. Cyst fluid, biochemical changes and computerised tomographic findings.

The concentrations of five biochemical substances were studied in cyst fluid from 49 cystic intracranial tumours and the findings were compared with the computerised tomographic (CT) scan and histological appearances of the tumours. The attenuation of the cyst wall on unenhanced CT was found to be related to cyst fluid alkaline phosphatase levels. Enhancement of the cyst wall with contrast medium was associated with higher levels of protein, cholesterol, alkaline phosphatase, phosphohexose isomerase (PHI) and  lactate dehydrogenase (LDH) in the cyst fluid. Lesions of high grade malignancy had higher levels of protein, cholesterol, alkaline phosphatase, LDH and PHI than lesion of low grade malignancy and also higher levels of alkaline phosphatase, LDH and PHI than benign lesions. Oedema around a lesion was associated with increased malignancy.


Normal human aging and cerebral vasoconstrictive responses to hypocapnia.

Cerebral vasoconstrictive capacitance was measured during voluntary hyperventilation hypocapnia in 22 healthly normal volunteers aged 21--65 years by serial 133Xe inhalation estimates of rCBF by the initial slope index method of Risberg (ISI2) in the steady state followed by the hypocapnic state. End-tidal PCO2 was monitored by a capnograph. There was significant linear correlation between reduction of PECO2 and the ISI2 values. Significant reduction of cerebral vasoconstrictive response to hypocapnia was found with normal advancing age which is attributed to (1) minor atherosclerosis or loss of elasticity of cerebral vessels with advancing age, (2) the presence of an ischemic threshold during hyperventilation at which CBF tends to stabilize.


Central conduction time as an index of ischaemia in subarachnoid haemorrhage.

Central conduction time (CCT) has been measured in 12 healthy volunteers, and in 16 patients admitted to a neurosurgical unit following subarachnoid haemorrhage. Twelve of the patients were subsequently operated upon for the obliteration of an intracranial aneurysm. CCT has been found to have low standard deviation in control cases, and in the normal side following subarachnoid haemorrhage from aneurysms in the Circle of Willis, and to be prolonged during the development of ischaemic complications, either of the haemorrhage or following surgery. Evidence so far suggests that CCT may be useful as a monitor of developing ischaemia in association with surgery for subarachnoid haemorrhage.


Digestibility of raw and cooked starches from legume seeds using the laboratory rat.

The in vivo digestibility and growth responses to diets containing raw and cooked legume starches were determined using male Wistar rats. These starches were obtained from seven legumes including smooth- and wrinkled-seeded field peas, navy beans, kidney beans, garbanzo beans, mung beans and lentils. Wheat and potato starch diets were fed for comparative purposes. With the exception of potato and the field pea starches, rats fed uncooked starch diets had higher weight gains than those fed cooked starch diets. The starches from wheat and all legumes, excluding the high-amylose wrinkled pea, were nearly 100% digestible but the legume starches reduced the digestibility of casein protein by 3 to 4%. Raw potato starch was shown to be only 57% digestible. The starches from potato and wrinkled pea reduced the digestibility of casein protein to 87% and gave high cecum weights. These characteristics were not altered by cooking the starch of wrinkled pea. The starches of smooth-seeded peas, lentils and all beans were highly digestible, showed no adverse effects on growth and were comparable to wheat starch in this evaluation.


Effect of bran and cellulose on lipid metabolism in obese female Zucker rats.

The effects on lipid metabolism of bran and cellulose added to a low-cholesterol purified diet were studied in female obese Zucker rats. The obese Zucker rat was chosen for the experiment because of its sensitivity to dietary changes with regard to lipid metabolism. Cellulos, as well as bran, had an effect on lipid metabolism, which is expressed as an increase in the excretion of fecal bile acid and cholesterol and, in the case of bran feeding, as a decrease in liver cholesterol level and an increase of fecal fat excretion. The increased excretion rate of cholesterol and bile acids did not result in a reduction of the plasma cholesterol levels, which suggests a compensatory mechanism in the form of either an increase of hepatic cholesterol synthesis and/or changes within the body cholesterol pools. The increased excretion of fecal fat that occurred when bran was added to the diet, is not likely to influence cholesterol metabolism, since fecal fat excretion only appeared to form a small percentage of the total fat intake. Bran as well as cellulose caused a significant increase in fecal wet weight and a decrease in transit time. Though both cellulose and bran are capable of binding bile acid, cholesterol and/or fat, the intestinal transit time and the fecal bulk might also be a cause of increased steroid excretion. The fact that our results are inconsistent with those of some investigations described in the literature but in agreement with the findings of other workers, again stresses the primary need for a better chemical characterization of the various fiber sources.


The influence of carrier of gustatory stimulation on the cephalic phase of canine pancreatic secretion.

The pancreatic secretory responses of dogs to various taste stimuli were examined in this study. Additionally, taste preferences were examined in 24-hour exposure tests to taste stimulus solutions as well as in short exposure tests to taste solutions mixed with commercial stock diet. The liquid and solid food preference tests produced quite different results. In dogs with cannulated gastric and duodenal fistulas, gustatory receptors were stimulated orally with 100 ml of taste stimulus solution (water 0.05 M monosodium glutamate (MSG), 0.05 M citric acid or 0.3 M sucrose) mixed with 25 g of a carrier (commercial stock diet, purified diet or cellulose). Pancreatic secretory responses to the taste stimuli varied with the type of carrier. Stock diet carrier was a better stimulant than the purified diet for both protein output and volume flow. Taste stimuli with a cellulose carrier did not produce any pancreatic response at all. The differences in responses to the different carriers were greater than the differences between taste stimuli when the same carrier was used. This experiment indicates that gustatory stimulation does influence the function of pancreatic secretion depending on the carriers used.


Effect of dietary mineral composition on nutritional equivalency of amino acid mixtures and casein in rats.

The effect of dietary mineral composition on the quality of amino acid mixtures and intact casein was examined in growing rats fed for 28 days under "conventional" conditions. When 25% demineralized casein (DC) was the sole dietary protein source, the widely-used mineral mixture by Harper (MMH) supported growth poorly (3.2 g/day), but a new formula mineral mixture (MM2) containing sufficient amounts of zinc gave a growth rate of over 8 g/day for 21 days. With a crude casein (CC) diet, rats grew at the same rate regardless of mineral mixtures. The growth-supporting power of amino acid mixtures, one of which simulated casein (AA-A) and another patterned after Rogers and Harper to give maximal growth of rats (AA-B), was compared with those of DC and CC with addition of MMH or MM2. When the protein source was DC, AA-A or AA-B, MM2 significantly improved the growth over that of rats fed MMH. The growth-stimulating effect of MM2 was greater when added to DC diet than when added to AA-A diet. When MM2 was added to AA-B diet, the growth rate greatly increased and reached that of rats fed DC diet containing MM2 (over 8 g/day), showing a nutritional equivalency between the amino acid mixture and intact protein. Drawbacks inherent in MMH did not appear with CC diet, because CC contained considerable amounts of zinc. When a highly purified amino acid-sucrose diet is used, dietary minerals become most limiting for growth even under conventional conditions. Thus, the previous conflicting results concerning nutritional equivalency of amino acid mixtures and protein can be explained by inadequate mineral sources.


Effects of magnesium deficiency on parturition and uterine involution in the rat.

The effects of moderate magnesium deficiency on the outcome of pregnancy, the process of parturition and uterine involution, were studied in successive experiments using Sherman rats. Females were fed purified diets containing 0.110 or 1.500 g Mg/kg throughout pregnancy and lactation. This magnesium deficient diet decreased the plasma magnesium but did not affect the number of pregnant rats or the weight of females at parturition. There was no change in the weight and size of litter. The number of still births was not significantly increased. The parturition process was observed; abdominal contractions were less obvious in deficient animals than in controls, and they were often not noticeable. Parturition was slightly lengthened in deficient rats. The major effects of magnesium deficiency occurred during lactation when the dam lost weight and the growth of her young was reduced. The uterine weight and its collagen content was higher and the collagen solubility was lower in the deficient rats than in controls between 2 and 10 days post partum. The delay in uterine involution could be prevented by provision of a magnesium supplement after parturition.


Effect of excess dietary methionine on the catabolism of cysteine in rats.

The effect of excess methionine (MET) on cysteine (CYS) catabolism was investigated in rats prefed either a control (10% casein + 0.3% L-MET) or high-MET (10% casein + 3.0% L-MET) diet for 50 or 20 days. The activities of cysteine dioxygenase, cysteine desulfhydrase and cystathionase were increased in high-MET rats to levels 5.9, 2.7 and 2.7 times, respectively, those of control rats after 5 days and to 2.9, 2.0 and 2.7 times control levels after 20 days. Cysteine aminotransferase and cystathionine synthase activities were increased to 1.5 and 1.7 times control values after 5 days but were not significantly different from control values at 20 days. Following gastric intubation of 5 g of an L-amino acid diet containing 0.2% L-[35S]CYS, the 24-hour urinary exretion of 35SO4, [35S]taurine and total 35S (% of administered dose) and the [35S]taurine:35S and [35S]taurine:35SO4 ratios were increased in rats prefed excess MET for 5 or 20 days. When 2.6% L-[35S]CYS was administered similarly, no significant differences between high-MET and control rats were observed. However, the [35S]taurine:35S and [35S]taurine:35SO4 ratios were elevated in both high-MET and control rats given 2.6% L-[35S]CYS over those for control rats fed 0.2% L-[35S]CYS. The increase in cysteine dioxygenase activity and the increase in [35S]taurine:35SO4 ratio in rats fed excess MET or given a load dose of CYS suggest that the cysteine sulfinic acid pathway plays a major role in the regulation of CYS degradation.


Effect of prolonged starvation on substrate uptake in the isolated perfused rat heart.

The pattern of substrate uptake by the heart in prolonged starvation, when lipid reserves are approaching depletion, has been examined. The classical Langendorff perfused heart preparation was employed to determine substrate uptakes in male rats fed ad libitum or starved for 7 days. Levels of metabolites in "arterial" and "venous" perfusion media and in heart tissue were determined by fluoroenzymatic assays, with the exception of palmitic acid which was analyzed by gas chromatography. It was found that glucose is the principal fuel of oxidation in perfused hearts of ad libitum-fed rats, whereas palmitate (FFA) is the major fuel of oxidation in perfused hearts of starved rats, followed by lactate, glucose, beta-hydroxybutyrate, pyruvate and alanine. Such changes might be related to some of the alterations in the metabolic pathway (e.g., glycolytic inhibition) in prolonged starvation.


Effects of vitamin B-12 deprivation on phospholipid fatty acid patterns in liver and brain of rats fed high and low levels of linoleate in low methionine diets.

Experiments were conducted to determine how 20 weeks of deprivation of vitamin B-12 (B-12) would influence polyunsaturated fatty acid (PUFA) patterns in cerebral and liver phospholipids of female rats. All experimental diets included 24% soybean protein and either 3.5 of 0.35% of linoleate (18:2). Deprivation of B-12 and restricted intakes of 18:2 significantly inhibited growth of the rats. Rats depleted of B-12 had 6.7 times more methylmalonic acid in their liver, and significantly more odd-numbered acids (15:0 + 17:0) were present in phosphatidyl choline (PC) of their liver and cerebrum. Deprivation of B-12 promoted 63.3 to 97.3% increases of 18:2 in PC and phosphatidyl ethanolamine (PE) of the liver. Rats deprived of B-12 had significantly less arachidonate (20:4 omega 6) and 22:5 omega 6 in their liver PC, as well as smaller amounts of 20:4 omega 6 and 22:6 omega 3 in their cerebral PC. Some of the observed changes appear to be due to a significant interaction between the effects of B-12 and linoleate. Changes in PUFA patterns of cerebral and hepatic PC suggest that B-12 deprivation may interfere with the conversion of 18:2 omega 6 leads to 20:4 omega 6 leads to 22:5 omega 6. Some of the observed changes may also be related to an inhibited ability to convert PE to PC.


Maternal-fetal transfer of ascorbic acid in the guinea pig.

Placental transfer of ascorbic acid was studied in the guinea pig using an in situ placental perfusion technique. A total of 14 animals were studied during their last week of gestation. The fetus was shown to have higher plasma total ascorbic acid (TAA) levels than the mother prior to maternal ascorbic acid infusion. However, following maternal venous infusion this normal gradient for TAA (fetal greater than maternal) disappeared and a new gradient was established (maternal greater than fetal). As maternal plasma TAA levels rose, the level of TAA in the placental perfusate steadily increased to a maximal concentration of approximately 0.85 mg/dl. This occurred when maternal plasma TAA levels were above 3.0 mg/dl. These results demonstrate that a saturable or carrier-mediated transport mechanism is involved in the placental transfer of ascorbic acid in this species. The apparent Vmax (the maximal transport rate by the saturable system per gram placenta) and the Kt (or one-half saturation concentration) were estimated to be 8.3 nmoles/minute and 0.12 mM, respectively. Additional results are presented to suggest that dehydroascorbic acid (DHA) may be the predominant form of the vitamin crossing the guinea pig placenta.


Adipocyte cholesterol storage: effect of experimental hypercholesterolemia in the rat.

In order to more clearly define the influence of adipocyte size and plasma cholesterol on adipose tissue cholesterol storage, hypercholesterolemia was induced in male Fisher rats at a time when body weight and adipocyte size become fixed. In one experiment (experiment 1), increasing amounts (0, 0.05, 0.5 and 5.0%) of dietary cholesterol were added to a fat-free, purified diet (sucrose-casein-cellulose) fed to 1 year old virgin males. In experiment 2, retired breeder rats were fed 0 or 5% cholesterol, with and without corn oil supplementation of the purified diet. The plasma cholesterol responses (in experiment 1) to the various dietary cholesterol levels were in the order 0 = 0.5 greater than 0.05 greater than 5.0% = stock diet. In experiment 2, however, rats fed cholesterol had higher plasma cholesterol values than those fed the cholesterol-free diet. When total cholesterol concentration per 10(6) adipocytes was examined in four adipose depots, it was found that adipocyte cholesterol content tended to increase with increasing levels of circulating total cholesterol, regardless of the cholesterol content of the diet. The accretion of cholesterol in adipocytes was accompanied by enhanced storage in the esterified form, a response very similar to that of liver in these experiments but unlike skeletal muscle. It is concluded that adipose tissue participates physiologically in the response to hypercholesterolemia in the rat, but that the response may depend upon the nutritional or metabolic state of the animal prior to cholesterol feeding (young rats versus retired breeders) and is not similar in all adipose tissue depots.


Effects of tristearin, triolein and safflower oil diets on cholesterol balance in rats.

Diets containing relatively homogeneous triglycerides composed of 18-carbon chain saturated, monounsaturated or polyunsaturated fatty acids were fed to rats. Cholesterol absorption and turnover were studied. Cholesterol absorption was significantly less in rats fed tristearin than in animals fed triolein or safflower oil. Cholesterol removal from plasma was fastest in rats fed tristearin and slowest with safflower oil and triolein. Plasma cholesterol levels were lowest with tristearin and highest with safflower oil. Increased cholesterol in high density lipoproteins was observed with tristearin and triolein. Lymph and hepatic cholesterol, and lymph triglycerides were highest with safflower oil, suggesting endogenous mobilization. Cholesterol production was least with triolein. Sterol synthesis was greatest with tristearin, perhaps attributable to decreased negative feedback analogous to effects of cholestyramine. Differences in lipoprotein composition observed with the various diets are important since effects on particle size and shape may influence removal mechanisms. The mechanisms underlying the different effects of dietary triglycerides on sterol absorption and metabolism remain to be elucidated.


Effects of diets of homogeneous saturated triglycerides on cholesterol balance in rats.

The effects of a diet of 10% homogeneous triglycerides of 12 to 18-carbon chain saturated fatty acids on cholesterol absorption and turnover were studied in rats. Cholesterol absorption was successively significantly less in rats fed tristearin than in groups fed tripalmitin, trimyristin and trilaurin. Lesser fatty acid absorption may explain the differences in part, since cholesterol absorption was significantly correlated with fat absorption. Cholesterol removal from plasma was fastest in rats fed tristearin. Plasma cholesterol levels were increased with the trilaurin diet although the rate of cholesterol accumulation in lymph after gavage was slower with trilaurin. Lymph triglycerides were highest with trilaurin and trimyristin diets perhaps indicating endogenous mobilization of triglyceride for lipoprotein formation. Lymph triglycerides were, however, decreased with tristearin. Sterol turnover (production, absorption plus synthesis) was increased with tristearin or trilaurin by kinetic or balance methods.


Vitamin C deficiency in growing willow ptarmigan (Lagopus lagopus lagopus).

Willow ptarmigan chicks raised on a diet containing 265 mg ascorbic acid/kg develop scury-like symptoms and die by 4 weeks of age. If blueberry plants are given as an ad libitum supplement to this diet, the malady is prevented. We have described the clinical, pathological and histological changes which accompany this malnutrition and conclude that they are in accord with the description of scurvy in guinea pig and man. Biochemical determination of ascorbic acid synthesis in the kidney of ptarmigan chicks indicated a rate of synthesis five times that found in livers of growing white rats. Blueberry plants and many other plants found in the natural diet of ptarmigan chicks contain 2,000 to 5,000 mg ascorbic acid/kg dry weight. Feeding experiments showed that the pathological signs were avoided and that already afflicted chicks recovered if the vitamin C content of the diet was raised to 750 mg/kg dry weight of food. Since the food intake of the chicks was 5 to 8 g/day the daily requirement of external vitamin C is about 150 mg/kg body weight. To our knowledge this is the first example of an animal which, while producing vitamin C itself, requires substantial amounts of external vitamin C to survive.


Drinking problems among employed, unemployed and shift workers.

This study investigated the relationships between drinking problems and the following: current employment status, current occupation, unemployment, shift work and alcohol-related problems. The study involved a household survey of 993 persons in Durham, an area near Toronto. A scale of 17 alcohol problems and symptoms was used. It was found that the highest rates of problems were among shift workers and the unemployed. The workers most likely to have serious problems were in processing/manufacturing, transport, artistic/literary/recreational and sales areas. Males with serious problems and shift workers reported drinking more when unemployed. Sanctions for work-related drinking problems, even for those with serious dependency, were rarely applied. This study suggests that priority targets for programs to assist employees with drinking problems should be males in processing/manufacturing, transport, artistic/literary/recreational areas and sales.


Middle life crisis and industrial workers.

Psychiatric consultation with a large utility company has uncovered a unique manifestation of the middle life syndrome. Employees with 20 or more years of service, referred to our psychiatric group, have in common such issues as "institutional transference," unfulfilled employee vocational dreams and fantasies, with concurrent inability to adjust to technological, geographical and personnel changes. The author suggests personnel programs and policies which might help to deal preventively with these problems before employees reach middle life. Methods are suggested in which corporation changes might be more sensitively instituted to meet the psychological needs of employees.


Mortality of pesticide applicators.

Information has been obtained on a cohort of professional pesticide applicators which will be followed prospectively. The cohort consists of 16,126 males employed for three months or more between 1967 and 1976 by any of three nationwide pest control companies. Deaths which occurred between 1967 and 1976 were reported by the Social Security Administration as a result of a search of its records. Overall, 311 deaths were ascertained, giving a standardized mortality ration (SMR) of 84. SMRs were over 100 for three causes of death--cancer of the lung (115), cancer of the skin (173) and cancer of the bladder (277). The confidence intervals of two of these ratios include 100, and the observed numbers therefore do not differ significantly from those expected. For bladder cancer the excess is on the border of statistical significance (p less than 0.05). The excess of deaths from lung cancer was not seen for applicators classified as termite control operators, a group more likely to be exposed to chlordane and heptachlor. There were significantly low SMRs for cancer of the digestive organs (46) and for other diseases of the digestive (55) and respiratory (29) systems. Deaths from cerebrovascular disease were also less than expected, though not significantly so.


The effect of constructive coercion on the rehabilitative process. A study of the employed alcoholics in an alcoholism treatment program.

Two groups of employed men in an alcoholic rehabilitation program--one referred through an organized policy of constructive coercion and the other volunteer--were compared to test the efficacy of constructive coercion in the rehabilitation process. It was found that the patients referred by constructive coercion were younger, had fewer psychosocial problems, had a higher percentage who were abstinent and had higher rates of compliance with follow-up. A policy of constructive coercion allows earlier identification of workers with alcohol problems and improves the chances for a positive treatment outcome.


Lung cancer mortality among iron foundry workers.

The present study was designed to test earlier findings of increased risk of lung cancer among iron foundry workers and to define the cause of the risk. The subjects were 3,425 workers with at least one year's employment in an iron foundry sometime between 1918 and December 31, 1972. The number (51) of cases of lung cancer which occurred prior to December 31, 1976 was statistically significantly higher than that expected, i.e., 35.3 based on proportional mortality. Molders and casters were determined to have the highest excess risk in a case-control study among the cohort. The worker groups with high exposure to polycyclic aromatic hydrocarbons (PAH) experienced a lung cancer risk higher than that of other groups, but the difference was not statistically significant.


Facsimile epithelioid cells obtained from stimulated peritoneal macrophages and their secretory activity in vitro.

Mouse peritoneal macrophages collected after exposure to new born calf serum in vivo were found to have some of the morphological and ultrastructural features attributed to epithelioid cells. These features were accentuated by short term culture in vivo or in vitro. Three accepted varieties of epithelioid cell were reproduced, i.e., those with predominant rough ER, those with predominant smooth vesicles and the plasmacytoid variety. Cells resembling fibroblasts were not seen, nor were lymphoid cells. The facsimile epithelioid cells had considerable secretory activity for a range of macrophage enzymes. They retained the phagocytic capacity and the surface receptors of macrophages but to a reduced extent. It is suggested that epithelioid cells are a form of stimulated macrophage, especially effective in enzyme secretion and liable to appear after excitation of the cell membrane by pinocytosis rather than phagocytosis.


The normal parathyroid gland at autopsy: the significance of stromal fat in adult patients.

Traditionally half of the cell population of the adult parathyroid gland is considered to be stromal fat. A marked decrease of stromal fat has been observed at autopsy of adult patients, the functional significance of which is unknown. In order to investigate this phenomenon, the stromal and parenchymal fat of the parathyroid glands of 33 adult patients who died with no known hormonal abnormalities were evaluated. Stromal fat was much less than 50 per cent, i.e., less than 10 per cent., in the majority of cases, while parenchymal fat was ample in all cases. This finding, especially if compared to cases with hyperparathyroidism, indicates the lack of functional specificity of change in stromal fat, whereas, alteration in parenchymal fat appears to be a better anatomical register of normal or abnormal parathyroid function.


Peribronchiolar fibrosis following acute experimental lung damage by cadmium aerosol.

Following exposure to an aerosol of 0.1 per cent. (0.005M) cadmium chloride in physiologic saline, rat lungs were examined at 1 hour, 1, 2, 3, 4, 5, 7, 10 and 21 days. Light microscopy showed that damage was most marked about respiratory bronchioles with a prominent increase in interstitial cells. Up to 3 days the intestitial cells were closely packed and monocytic in type, but on the fourth and fifth days, the cellular density had decreased and elongated cells resembling fibroblasts appeared. By 7 days the interstitial cells were predominantly fibroblastic. Ultrastructurally the fibroblasts were active with prominent rough endoplasmic reticulum and numerous, single, haphazardly scattered collagen fibrils in lacunae at the cell margins. At 21 days after injury, interstitial collagen was seen as well organised, mature bundles. The fibrosis was seen in a peribronchiolar position with distoration of the bronchiole and adjacent alveoli. We suggest that the peribronchiolar localisation of fibrosis is the probable cause of centriacinar emphysema resulting from acute cadmium fume poisoning in man.


Scanning electron microscope studies of some normal and diseased conditions of mammalian skin as revealed in leather manufacture.

Sheep, goat and bovine skins, as leather, were examined. The surface contours of dermal response to sunburn, facial eczema, rape scald, and demodicosis are illustrated. In sunburn, demodicosis and rape scald, finger-like and ridge pattern projections had developed. In the photo-sensitive condition of rape scald and facial eczema distension was apparent, and in addition in rape scald reactions of contrasting nature involving hair follicles indicated a considerable disorientation of the skin. The transition from str. basale to str. corneum in bovine epidermis has been examined in leather from which the epidermis had unintentionally been incompletely removed in the course of manufacture, during attack on the keratinous tissue by hydrosulphide ions at high hydroxyl ion concentration. A "pore" presumably related to the position of the nucleus was observed in the outer surface of each of the cells in each layer exposed by the attack. The walls of the basal and adjacent cells appeared remarkably sturdy. As judged from the basal cells the intercellular cement (cell coating) disappeared before the cell wall degraded, but intercellular bridges remained clearly visible in the prickle cell layer, while towards the exterior, adjacent cell walls appeared more closely knit and the str. corneum (residues of which were observed around the follicles) appeared to lie in sheets. Discrete and fibrous cell components were exposed. At the latest degree of degradation observed in the basal cells the wall had reduced to a fibrous network.


Budd Chiari syndrome from myosarcoma of right atrium.

A 50-year-old man presented with abdominal pain followed by marked liver and renal dysfunction. Although liver scan appearances were not diagnostic, at laparotomy a tense, enlarged liver was found with thrombosis of the inferior vena cava. Despite full supportive measures the patient died within a month of laparotomy. Subsequent necropsy confirmed the diagnosis of Budd Chiari syndrome and revealed the primary cause to be a myosarcoma of the right atrium, an occurrence hitherto unreported.


Fasciola hepatica in rats: transfer of immunity by serum and cells from infected to F. hepatica naive animals.

Immune, hyperimmune, and nonimmune serum samples were collected from inbred rats following 10 to 15 weeks of one [5 metacercariae (mc)/rat], two (5 mc followed by 30 mc/rat) or no (uninfected) exposure to Fasciola hepatica. Lymphoid cells also were collected from these donors. Inbred, naive rats in groups receiving immune serum, hyperimmune serum, nonimmune serum (serum control), immune cells, hyperimmune cells, and nonimmune cells (cell control) received intraperitoneally either a total of 20 ml of serum or a total of 3 x 10(8) viable lymphoid cells. A challenge infection of 30 mc/rat was administered orally at about the time of serum or cell transfer. The transfer of immunity was evaluated by examining recipient rats for parasites 4 and 8 weeks after challenge. Some hematological parameters and the precipitating antibody response of the recipients were monitored also. Hyperimmune serum, unlike immune serum, consistently provided a significant degree of protection in recipient rats. The precipitating antibody titre of this serum was higher than that obtained from the immune donor group. The importance of a second sensitization to obtain sufficiently potent serum was demonstrated. Lymphoid cells from infected donors did not consistently confer protection on recipients. Thus, the expression of protective immunity against F. hepatica seemed to be more dependent on the presence of antibodies than on cells. The hematological parameters of the recipients, in general, supported this observation. The precipitating-antibody response of protected rats was lower than that of unprotected animals following challenge, presumably because the development of fewer worms in the former provided less antigenic stimulation.


Isolation and characterization of surface antigens from Schistosoma mansoni. I. Evaluation of techniques for radioisotope labeling of surface proteins from adult worms.

Radiolabeled surface proteins of adult Schistosoma mansoni were prepared by in vitro labeling of whole worms, and by labeling freeze-thaw surface membrane extracts. Incorporation of 125I into surface proteins was attempted using the lactoperoxidase, chloramine-T, iodosulfanilic acid, and Bolton-Hunter methods. Radiolabeling of whole worms with lactoperoxidase, chloramine-T and iodosulfanilic acid yielded a single protein peak (mol wt greater than 100,000) on SDS-PAGE, and showed considerable incorporation of label in the lipid fraction. Bolton-Hunter labeling of whole worms yielded four major peaks with molecular weights of 100,000, 60,000, 30,000 and 21,000, and minor peaks with molecular weights of 26,000, 36,000, 43,000, 68,000 and 78,000; three of the four major peaks corresponded to prominent bands in Coomassie blue-stained gels. Although carbohydrate-labeling techniques were not successful, a single carbohydrate band, molecular weight greater than 100,000, was detected was PAS staining. Radiolabeling of freeze-thaw extracts yielded results similar to those obtained with whole worms. Electron microscopy revealed the tegument to be left intact and undamaged after labeling with the Bolton-Hunter reagent.


Adoptive transfer of protective immunity in experimental schistosomiasis in the mouse.

Passive transfer of immune serum alone did not confer protection to recipient mice irrespective of the routes of serum transfer or cercarial challenge of Schistosoma mansoni. Mice that received both sensitized cells and immune serum were protected against challenge by subcutaneous injection of cercariae but not by percutaneous exposure. The immune serum could be transferred as late as 8 days after subcutaneous challenge, suggesting that the protection was afforded in part by a late parasite killing mechanism which functions after the schistosomula have migrated through the lungs.


The purine phosphoribosyltransferases of Crithidia fasciculata.

The purine phosphoribosyltransferases of Crithidia fasciculata were identified and some of their properties described. The organism possesses three separate enzymes for the production of AMP, IMP, and GMP. The evidence for this comes from the observed differences in elution patterns from gel filtration columns, differences in heat sensitivity, and especially the clear separation of hypoxanthine phosphoribosyltransferase from guanine phosphoribosyltransferase by affinity chromatography on GMP-agarose. APRTase is activated most efficiently by Zn++, whereas HPRTase and GPRTase are activated most effectively by Co++. In no case did the product mononucleotides produce strong inhibition of the transferase activities.


The use of sodium taurodeoxycholate for excystation of Eimeria tenella sporozoites.

As an in vitro excystor, sodium taurodeoxycholate (TDC) released 80--90% Eimeria tenella sporozites, in contrast to 0--15% excystation by six other bile salts or bile extracts, and pooled chicken bile in 90 min at 37 C with continuous agitation. Pooled chicken bile required 4 to 4 1/2 hr to excyst similar percentages of sporozoites. Prolonged incubation with other bile salts and bile extracts excysted most sporozoites, but killed them. When the incubation temperature was raised to 44 C, TDC excysted 100% of the sporozoites in 60 min. In all other bile salts or bile extracts, the percentage of excystation increased greatly at 44 C, but none equalled that of TDC. The molecular similarity of TDC to a naturally occurring bile salt of chickens is presented as an explanation for the superior performance of TDC as an excystor. Data are examined to minimize the possibility that excysting activity of TDC can be attributed to other bile salts present at impurities.


De novo synthesis of methionine in normal and Brugia-infected Aedes aegypti.

Crude extracts of normal, adult Aedes aegypti were able to form methionine from homocysteine in the presence of 5-methyltetrahydrofolate (MeFH4) but not betaine. The requirements for the reaction, including a need for vitamin B12, S-adenosylmethionine (SAM), and a reducing system, indicated that it was catalyzed by MeFH4:homocysteine transmethylase (methionine synthetase). The general properties of A. aegypti methionine synthetase were found to be similar to those of the analogous enzyme from bacterial and mammalian sources, except that its apparent affinity for SAM was significantly lower. Extracts of normal, adult A. aegypti females (5 days after emergence, as well as 7 and 12 days after they fed upon uninfected jirds) synthesized methionine at a rate of 0.6 nmole per hr per mg protein. Extracts of female mosquitoes prepared 7 and 12 days after they fed upon Brugia pahangi-infected jirds synthesized methionine at double the normal rate. Because methionine formation by extracts of adult B. pahangi could not be detected, it is probable that methionine synthetase activity increased in the arthropod host in response to filarial infection.


Fine structure of the tegument of Mesocestoides tetrathyridia by scanning and transmission electron microscopy.

The tegumental surface of tetrathyridial stages of the tapeworm, Mesocestoides corti, was studied by scanning and transmission electron microscopy. Two structural types of microvilli were observed--blade-shaped or conical ones, and elongated, slender microvilli. The distribution and relative frequency of the two types of microvilli differs in different areas of the body surface. Host peritoneal cells were observed attached to the blade-shaped microvilli by slender cytoplasmic projections.


A unicellular endocrine gland in cestodes.

Unicellular glands are reported from the scolex and anterior neck region of Hymenolepis diminuta and H. nana. Despite positive staining reactions with the presumptive neurosecretory stains, paraldehyde-fuchsin and chrome-alum-hematoxylin, ultrastructurally these glands exhibit many non-neural characteristics. Glandular cell processes are frequently found in close proximity to muscular tissue, particularly in the suckers, suggesting a regulatory role in muscle modulation as a possible function. Two types of putative, neurosecretory cells are reported from the cephalic ganglia and the lateral nerve cords. Neurosecretory regulation of the unicellular endocrine glands is postulated based on the lack of direct innervation of the glands and the frequent close proximity of axons containing putative, neurosecretory granules.


Intraerythrocytic parasites in rodent populations of Connecticut: Babesia and Grahamella species.

A total of 612 Peromyscus leucopus, 11 Microtus pennsylvanicus, 21 Clethrionomys gapperi, and 4 Tamias striatus was collected in Connecticut and examined for Babesia and Grahamella during 1976 and 1977. Babesia antibodies were detected in sera of 9 P. leucopus collected from 4 sites. Babesia parasites were not detected in the blood smears of captured rodents. Subsequent splenectomy and subinoculation of blood from these rodents into susceptible animals failed to induce disease and no Babesia was isolated. Six of 10 P. leucopus inoculated with a Shelter Island, New York strain of B. microti remained infected for 3 1/2 months. Indirect fluorescent antibody titers of experimentally infected P. leucopus ranged from 1:8 to 1:256. Prevalence of Grahamella peromysci infection, as determined from examinations of blood smears of P. leucopus, was 13%. This infection rate is a conservative estimate because parasitemia is difficult to detect in intact animals. Twenty of 58 P. leucopus, taken at 2 sites and with negative blood smears for G. peromysci, developed parasitemia after splenectomy.


Laboratory infection of blackflies (Simuliidae) and midges (Chironomidae) by the mosquito mermithid, Romanomermis culicivorax.

Penetrating infective juveniles of Romanomermis culicivorax usually killed first-stage larvae of Chironomus maturus Johann., Chironomus sp., Simulium damnosum Theo., and S. venustum Say. Nematodes were melanized and died after they entered fourth stage larvae of 2 chironomid species, but no host reaction was evident after entry into fourth-stage blackfly larvae. In contrast, the nematodes initiated development in the latter hosts, which died before the nematodes completed their development.


Incidence of infection and host specificity of Cuterebra tenebrosa in bushy-tailed wood rats (Neotoma cinerea) from central Washington.

Cuterebra tenebrosa Coquillett bot flies were studied under natural and laboratory conditions in bushy-tailed wood rats and 7 other small mammal host species. Larvae demonstrated strong host specificity for Neotoma cinerea. Monthly trapping samples of wood rats in central Washington showed infection peaks of 65--70% in May and 30--40% in late summer. In laboratory-induced infections, wood rats supported 7 larvae without host mortality. Natural infections in trapped rats ranged from 1 to 6 per host. Larvae developed in lateral and dorsal warbles in laboratory and natural infections. Few wood rats demonstrated evidence of acquired immunity in repeated infections over 2 years.


Helminths of shorebirds from the Texas Gulfcoast. I. Digenetic trematodes from the long-billed curlew, Numenius americanus.

Trematodes found in 10 Numenius americanus from the Galveston area included Pelmatostomum americanum sp. n. (Echinostomatidae) from the intestine; Paratrema numenii gen. et sp. n. (Philophthalmidae) from the Bursa Fabricii and lower intestine; and the following previously known species, all representing new host records: Maritrema arenaria and Probolocorphye glandulosa (Microphallidae); Lyperosomum oswaldoi and L. sinuosum (Dicrocoeliidae); Cyclocoelum obscurum (Cyclocoelidae); Himasthla rhigedana (Echinostomatidae); and Parorchis acanthus (Philophthalmidae). New taxa are diagnosed and H. rhigedana is redescribed.


Feather mites of the greater sandhill crane.

New taxa are described from Grus canadensis tabida: Brephosceles petersoni sp. n. (Alloptidae); Pseudogabucinia reticulata sp. n. (Kramerellidae); Geranolichus canadensis sp. n., and Gruolichus wodashae, gen. et sp. n. (Pterolichidae). Observations on resource partitioning by these mites are given.


Neottialges (Pelecanectes) ibisicola sp. n. (Acari: Hypoderidae) from the subcutaneous tissues of the white-faced ibis, Plegadis chihi (Ciconiiformes: Threskiornithidae).

Neottialges (Pelecanectes) ibisicola sp. n. is described from the subcutaneous tissues of the White-faced Ibis, Plegadis chihi, from west Texas. The new species is similar to N. (P.) plegadicola Fain, but differs from this and other species of the subgenus by idiosomal chaetotaxy, presence of a bifurcate apical extension on Tarsus III, solenidion phi on Tibia I less than 1/2 as long in the new species, lateroventral seta of Tibia I whiplike, structure of the genital sclerite and suckers, and presence of punctations on the dorsal idiosoma. The morphology and host-parasite relationships of the new species are compared with those of related species of hypopi from the host family Threskiornithidae.


Field study of the relationship between skin-sensitizing antibody production in the cottontail rabbit, Sylvilagus floridanus, and infestation by the rabbit tick, Haemaphysalis leporispalustris (Acri: Ixodidae).

The resistance of cottontail rabbits to tick feeding appears correlated with the rabbits' development of skin-sensitizing antibodies. Resistance appeared to be greatest in adult rabbits which had been repeatedly infested with ticks. Rabbits with little exposure to ticks, usually the young cottontails, showed little or no skin-sensitizing antibody present in their blood and usually had relatively high tick loads when compared with adult rabbits. Models used to interpret the data show promise as tools for predicting tick population fluctuations and, perhaps, incidence of vector borne disease outbreaks. The existence of resistance to tick attachment has important implications for the host-parasite relationship. The research lends support to the hypothesis that the resistance may function as a homeostatic regulatory mechanism capable of maintaining the size of the tick population in equilibrium with the size of the rabbit population. In this way, host resistance may be advantageous to the parasite as well as to the host.


Fascioliasis: similarities of the anemia in rats to that produced by infused proline.

Fasciola hepatica releases large amounts of proline into the bile of its host. Significant increases in the levels of other amino acids in the bile also occur. The present investigation examines whether proline and these other amino acids may play a role in inducing the anemia that frequently accompanies fascioliasis. In experiments, rats were infused intra-abdominally for 2 weeks with 1 of 3 solutions: 20.0 mM proline in saline, a mixture of 8 amino acids (excluding proline) each at 2.0 mM in saline, or saline only. At the end of the experiments 2 cc of blood was removed from each rat, via cardiac puncture. The heparinized blood was used to count erythrocytes and reticulocytes, and to measure hematocrit and mean corpuscular volume (MCV). Analysis of variance disclosed highly significant differences in erythrocyte counts, MCV, and reticulocyte counts among the 5 groups. A Student-Newman-Keuls test indicated that the Proline and Infected groups were not different from each other (except for MCV, where proline's effect was more severe) and that both groups differed significantly from the Amino Acid group, the Saline group, and the Control group. Hence, it appears that infused proline can cause an anemia similar to that induced by Fasciola.


Changes in the structure of Nippostrongylus brasiliensis intestinal cells during development from the free-living to the parasitic stages.

The ultrastructure of Nippostrongylus brasiliensis intestinal cells was examined in free-living, feeding second-stage larvae, infective, nonfeeding third-stage larvae, and parasitic, feeding third-stage larvae. The intestinal cells of second-stage larvae were characterized by a well-developed microvillar border, large numbers of ribosomes, Golgi complexes, rough endoplasmic reticulum, and nuclei with prominent nucleoli. The intestinal cells of infective, third-stage larvae had very few microvilli and the cells were extremely narrow. Few ribosomes, Golgi complexes, and little rough endoplasmic  reticulum were present. Nuclei did not contain nucleoli. When worms were introduced into an in vitro culture system, development of intestinal cells began. By 36 hr, microvilli were well differentiated and the cysoplasm contained numerous ribosomes and Golgi complexes, and rough endoplasmic reticulum, mitochondria, and nucleoli were prominent. These morphological changes were related to changes in the physiology of Nippostrongylus brasiliensis which occur during development from a free-living to parasitic form.


Trypanosoma brucei: in vitro propagation of metacyclic forms derived from the salivary glands of Glossina morsitans.

1 Metacyclic forms of Trypanosoma brucei obtained from the salivary glands of the tsetse fly, Glossina morsitans have been cultured for the first time in their infective forms for more than 200 days in continuous culture. The parasites were grown at 25 C and 30 C on a bovine embryonic spleen (BESP) feeder layer in buffered RPMI 1640 medium supplemented with 20% heat-inactivated bovine fetal serum (BFS) and 5% lactalbumin hydrolysate. Initial growth rate was enhanced when normal, noninfected, salivary glands were added to the cultures. The parasites thus cultured appeared like slender or intermediate blood stream forms which were infective to rats and mice. Addition of rat anti-T. brucei specific antiserum to the cultures caused agglutination of the parasites and rendered them noninfective. This study opens up new areas of investigating sleeping sickness. The cultured metacyclic parasites have the potential of being applied as antigens for controlling African trypanosomiasis.


Development, survival, and oviposition of the rabbit tick, Haemaphysalis leporispalustris (Packard) (Acari: Ixodidae), at constant temperatures.

The relationship between development, survival, and oviposition rates, and five constant temperatures is described for the developing and reproductive life stages of the rabbit tick, Haemaphysalis leporispalustris (Packard). Development was most rapid at 29.7 C for egg and larvae, and 35.6 C for nymphs. Survival was greatest between 14.7 and 29.7 C, but was reduced at 35.6 C for eggs and larvae. Oviposition was optimal between 19.9 and 29.7 C with a maximum mean daily oviposition of 253 eggs/female/day on the third day of oviposition at 29.7 C. Maximum mean total eggs per female produced was 1,157 with a range of 277 to 3,327. The total number of eggs produced per female correlated with the weight of the engorged female. Both linear and sigmoid curve equations were used to approximate the relationship between the temperature and development rates of eggs, larvae, and nymphs. The nymphs had the highest heat requirements of the 3 development stages. Comparisons with field host-parasite data indicate that the rabbit tick has a 2-yr life cycle in southwestern Nova Scotia.


Rallinyssus sorae sp. n. (Acari: Dermanyssidae: rhinonyssinae) from the nasal passages of the sora, Porzana carolina (Aves: Rallidae).

Rallinyssus sorae sp. n. is described from the nasal turbinates of the sora, Porzana carolina, collected in Maryland and Ohio. The new species is most similar to Rallinyssus verheyeni Fain but differs in number of setae on the female ventral opisthosoma, structure of the fixed and movable digits of the male and female chelicerae, chaetotaxy of legs I to IV, and presence of a sternal plate in the male. The taxonomy and host-parasite relationships of the various species of Rallinyssus are discussed.


A new genus of cyclopoid copepod (Chondracanthidae) parasitic on halibut from California inshore waters.

Auchenochondria lobosa gen. et sp. n. was recovered from the oral cavity of the California halibut, Paralichthys californicus (Ayers), collected in Agua Hedionda Lagoon, Carlsbad, California. The new genus is closely related to Prochondracanthus Yamaguti 1939, and Rhynchochondria Ho 1967, but can be distinguished from them by the possession of cephalothoracic processes, a long neck, a 2-segmented abdomen, and a distinctly 6-segmented first antenna. Auchenochondria lobosa gen. et sp. n. is the only known species of chondracanthid in which the mandible of the male is equipped with more teeth on both the convex and concave surfaces than that of the female.


Procyonostrongylus muelleri gen. et sp. n. (Metastrongyloidea: Angiostrongylidae) from the raccoon (Procyon l. lotor).

Procyonostrongylus muelleri gen. et sp. n. from under the epithelium of the epiglottis of Procyon l. lotor is distinguished by 1) the absence of lips; 2) a highly developed reinforced bursa with a deep terminal incision; 3) highly developed toothlike dorsal rays; 1) greatly reduced externodorsal rays; and 5) the terminal or subterminal anus and vulva in the female.


A case of isolated medial wall fracture with medial rectus entrapment following seemingly trivial trauma.

A case of isolated medial orbital wall fracture and medial rectus entrapment is presented. With minimal external evidence of trauma and lack of definitive evidence of fracture on plain films, a high index of suspicion if needed to diagnose this relatively unusual syndrome. The triad of: (1) retraction syndrome; (2) positive forced ductions in abduction; and (3) radiographic evidence of medial wall fracture on polytomography, will help the clinician to properly diagnose this condition. Epistaxis and subcutaneous emphysema, when present, should alert one to look carefully for a medial wall fracture.


Subperiosteal hematomas of the orbit in young males: a serious complication of trauma or surgery in the eye region.

Three documented cases of subperiosteal hematomas in the region of the orbital roof of young males are used to demonstrate the unpredictable appearance, the obscure nature, the complications and the treatment of this process. One case occurred in a 14-year-old boy following blunt head trauma and was cured by aspiration. The second case, in a 16-year-old boy, also resulted from blunt head trauma; it was associated with a large subgaleal hematoma and caused permanent blindness of the involved eye. The third case developed in an 18-year-old male as a complication of acute purulent endophthalmitis following an intraocular foreign body. The aim of this study is to separate subperiosteal hematomas and to show that it is a concise clinical entity with its own typical history, appearance and treatment.


Prognosis in traumatic cataract surgery.

Surgical results in 30 cases of traumatic cataracts using mainly aspiration and extraction techniques are reported. A corrected visual acuity of 6/12 or better was achieved in 64.3% of cases. Three eyes had light perception only. Early surgery using aspiration technique followed by contact lens correction is recommended for traumatic cataracts.


The Kasai operation (hepatic portoenterostomy) for biliary atresia--experience with 20 cases.

Twenty infants have undergone hepatic portoenterostomy at The Hospital for Sick Children in Toronto. Sigificant bile flow was obtained in six babies. No correlation was found between the size of the ducts in excised portal tissue and postoperative bile flow. Ascending cholangitis has not been a major problem. Progressive cirrhosis leading to portal hypertension is the main late problem in those patients who have had bile flow successfully reestablished.


Previous strabismus surgery and eye position under anesthesia.

We studied eye position under general anesthesia in 51 patients with concomitant esotropia or exotropia, divided into two groups. One group consisted of strabismus patients who had had no previous surgery. The second group consisted of strabismus patients who had undergone previous surgery on one (asymmetric) or both (symmetric) eyes. We found that both groups showed either no change or more divergence under general anesthesia in comparison to their preoperative state. Those patients who had had no previous surgery revealed an equal divergence in both eyes. This relationship also held true for those patients who had undergone symmetrical surgery in both eyes. However, those patients who had had surgery in one eye only showed more divergence in the operated eye than in the unoperated one. These findings reflect the mechanical--anatomical factors created by the surgery itself.


Neurogenic tumors and VIP-induced diarrhea.

The authors report a case of cervical ganglioneuroblastoma associated with intractable watery diarrhea and hypokalemia. The probable physiopathologic mechanism of the diarrhea and its relation to the vasoactive intestinal peptide secretion (VIP) by the tumor are discussed.


Diagnostic signs in the nystagmus compensation syndrome.

A summary of the diagnostic signs of the nystagmus compensation syndrome have been presented. A brief description of the present regimens of therapy is also included.