Mobius syndrome and limb abnormalities.

Most ophthalmologists are aware of the cranial nerve dysfunctions that have been associated with the facial diplegias of Mobius syndrome. However, many are not aware of the combined limb deficiencies and cranial nerve dysfunctions. Limb malformations have been associated with a spectrum of oral facial anomalies consisting of micrognathia, hypoglossia, microstomia, hypodontia, oral bands, and dysarthria. It has been suggested that the differences which exists between these entities may in fact represent a common etiology. The variability may be related to an intrauterine insult at slightly different times. The oral-facial anomalies associated with absence of limbs or of limb anomalies suggests a correlation between the limbs and the first visceral arch possibly within the second month of gestation.


Bilateral keratoconus in Crouzon's syndrome with unilateral acute hydrops.

Bilateral keratoconus was first observed at the age of 13 years in a boy born with Crouzon's syndrome. Corneal hydrops (acute keratoconus) occurred in one of the involved eyes at the age of 15 years. It does not seem that an occurrence of keratoconus in Crouzon's disease has been reported before.


Optic nerve hypoplasia in chondrodysplasia punctata.

A case of optic nerve hypoplasia in the Conradi-Hunermann form of chondrodysplasia punctata is reported. This is the first published report of such a case. The authors suggest that optic nerve hypoplasia in chondrodysplasia punctata may be the significant lesion of the optic nerve rather than atrophy as has been previously reported.


Myelinated nerve fibers associated with afferent pupillary defect and amblyopia.

A case is reported of myelinated fibers of the optic nerve associated with amblyopia and an afferent pupillary defect. The optic foramen on the involved side was larger; however, there were no other physical findings to which we could attribute the amblyopia and Marcus Gunn pupil.


Natural history and treatment of renal vein thrombosis in children.

The general features and problems of renal vein thrombosis in children are first discussed. The records of 11 children with this condition, 7 ill neonates and 4 older children with burns, are then reviewed, indicating the clinical course of the disease, how they were treated, the results, and pathological findings. From this study, the natural history is assembled and a protocol for treatment is proposed. Supportive therapy is necessary in all cases to correct dehydration and sepsis. Many children will develop a consumptive coagulopathy. Others will develop pulmonary emboli associated with thrombosis of the inferior vena cava. Anticoagulation should be achieved for these two conditions. Nonvisualization of affected renal units upon initial urographic examination virtually assures an atrophic, functionless kidney later. Nephrectomy will be required because of hypertension, persistent infection, and scarring. Thrombectomy may be attempted when bilateral nonvisualization on urography is associated with a positive venacavogram.


Congenital, bilateral, epithelial ingrowth into the anterior chamber.

Interior limbal staphyloma due to epithelial ingrowth into the anterior chamber appeared at birth in both eyes of a brother and sister born successively in a family of eight children. The possible etiopathogeny of such an uncommon occurrence is discussed.


Acute idiopathic scrotal edema.

A distinct clinical entity, acute idiopathic scrotal edema (AISE) has been previously characterized in the literature. Another six cases are reported. This clinical entity must be differentiated from testicular torsion and is of consequence for that reason.


"Acquired" congenital diaphragmatic hernia.

"Acquired" congenital diaphragmatic hernia (ACDH), has been defined as delayed or late appearance of a congenital diaphragmatic hernia after a documented time periol of postnatal life with no evidence of herniation. Three new cases are presented. This diagnosis has been characterized on the basis of a review of these cases and 14 additional patients from the literature. A classification based upon timing of herniation and state of pulmonary development is presented.


Osteomyelitis of orbital bones.

Clinical, radiological, and microbiological features of seven cases of osteomyelitis involving the orbital parts of the frontal, the maxillary, and the zygomatic bones are described. The cases were managed with antibiotics, curettage, and sequestrectomy. Problems in the correction of deformities due to circatrization are discussed. It is observed that a skin graft at second stage may be a success.


Massive gastric enlargement with delayed presentation of congenital diaphragmatic hernia: report of three cases and review of the literature.

In three cases of congenital diaphragmatic hernia presenting long after the newborn period, there was striking enlargement of the intraabdominal stomach. In each case there was herniation of the entire small bowel into the thorax and absence of a hernial sac. Despite the enormous capacity of the stomach, which was suggestive of obstruction preoperatively, no site of obstruction could be demonstrated at operation. This enlargement disappeared following surgical repair of the hernia.


Proptosis as presenting symptom of orbital foreign body.

An unusual case of orbital foreign body is presented. The foreign body had penetrated through a small wound of the upper lid and was asymtomatic for two years. Proptosis due to hyperostosis of the orbital roof was a presenting symptom of the foreign body.


Delayed appearance of a left posterolateral diaphragmatic hernia resulting in significant small bowel necrosis.

This is a case report of an infant who has a normal chest x-ray early in life and later developed a left posterolateral diaphragmatic hernia resulting in life-threatening bowel infarction.


Subcutaneous granuloma annulare("pseudorheumatoid nodule") of the eyebrow.

Subcutaneous granuloma annulare occurs either as a single or multiple lesion. When the ocular adnexa are involved, the lateral aspect of the eyelid and the lateral canthus are sites of predilection. These lesions occur chiefly in children and only rarely in adults. They have the same clinical (and histopathological) appearance as rheumatoid nodules and are, therefore, also known as "pseudorheumatoid nodules." Despite this similarity, these nodules are isolated lesions and are not related to systemic disease, including rheumatoid arthritis and rheumatic fever. The presently reported case exemplifies the characteristic clinical and pathological features of this disorder.


Histochemical criteria for the diagnosis of Hirschsprung's disease in rectal suction biopsies by acetylcholinesterase activity.

Histochemistry to demonstrate cholinergic fibers in rectal suction biopsies is a reliable method to diagnose or exclude Hirschsprung's disease. The histochemical criterion of a positive reaction consists of the presence of many coarse discrete cholinergic fibers in the muscularis mucosae and in the immediately subjacent submucosa, best assessed under medium power with the condenser lowered. A marked increase in cholinergic fibers in the lamina propria is seen only in some cases of Hirschsprung's disease. At least some cases of Hirschsprung's disease may be the result of destruction of ganglion cells by a viral infection in the intrauterine and early postnatal life.


Neuronal colonic dysplasia: an unusual association of Hirschsprung's disease.

A case of neuronal colonic dysplasia in association with Hirschsprung's disease is described. It is suggested that this condition be borne in mind when investigating operated Hirschsprung's cases having residual symptoms.


Chylous ascites: the first reported surgical cure by direct ligation.

A patient with apparently intractable chylous ascites was finally explored after the administration of preoperative lipophilic dye. This made identification of a leaking lacteal possible and ligation resulted in a cure.


Incidence of some surgically correctable congenital abnormalities in South Australia.

A retrospective 5 yr survey of the incidence of some neonatal surgically correctable congenital abnormalities in South Australia has been carried out. Meaningful figures have been obtained for the incidence, in terms of the live birth rate, of obstructive malformation of the gastrointestinal tract, major abdominal wall and diaphragmatic defects, and some anomalies of the genitourinary system. In the main, the incidence of these malformations is similar to that reported from other centers. However the incidence of exomphalos and small bowel obstructions is lower in this series than in others, and the incidence of tracheoesophageal and anorectal anomalies appears to be slightly higher in South Australia than in Victoria. The incidence of diaphragmatic defects, excluding esophageal hiatus, is very similar to that ascertained by the perinatal mortality survey carried out by Butler and Claireaux.


Neonatal arterial occlusion with ischemic limb gangrene.

Arterial occlusion in the extremity of a neonate is a rare event of obscure etiology. The diagnosis implies an urgent situation which may result in extremity gangrene and ultimate loss of limb. In contrast, early diagnosis and appropriate management should result in preservation of a normal limb. The key to successful management appears to be an awareness of this common clinical condition in an uncommon clinical setting.


Neonatal arterial occlusion.

A neonate with idiopathic brachial artery occlusion was recently treated at the San Bernardino County Medical Center. At birth, the right upper extremity was cold, pulseless and cyanotic. Arteriography demonstrated brachial artery occlusion, following which thrombectomy and postoperative heparinization resulted in a viable limb. This represents an unusual case of neonatal arterial occlusion with diagnostic preoperative arteriography and successful Fogarty thrombectomy. Possible etiological factors, treatment alternatives, and long term prognosis are discussed in this report.


A "second" radial artery for monitoring the perioperative pediatric cardiac patient.

The radial artery on the radial aspect of the wrist can be used as an alternative site of blood pressure monitoring and sampling. The anatomy of the radial artery in the wrist is reviewed and its clinical use is described.


Electrosurgical skin incision.

A controlled clinical study shows that there is little difference between skin incisions made with a scalpel or by electrosurgical instruments.


Left testicular and groin pain: an unusual presentation for perforated appendicitis.

A 12 yr old black male presented with a 3 day history of left inguinal and testicular pain associated with nausea, vomiting, and fever. Left groin exploration demonstrated a markedly inflammed patent process vaginalis containing purulent exudate. Concomitant abdominal exploration demonstrated a perforated gangrenous appendix with diffuse peritonitis.


High vasopressin concentrations in human umbilical cord blood--lack of correlation with stress.

Marked elevations in the vasopressin concentrations in human umbilical cord blood have been reported previously (4, 8). This could either be a part of generalized increase in the activity of fetal endocrine system at the time of birth, a phenomenon that has led to the concept of fetal participation in the onset of labor, or simply due to the stress of delivery. The present study is an attempt to examine the later possibility. Plasma vasopressin was determined by radioimmunoassay [9] in separately collected arterial and venous blood from the umbilical cords of 24 babies spontaneously delivered and 14 babies born after Caesarian Section in the absence of labor. Arterial acid-base determinations were done in each case. The Apgar Score was evaluated by one individual. In order to obtain a general idea of circulating concentration of this hormone in the neonatal period, vasopressin concentrations were determined in the systemic venous blood of 12 normal and 10 stressed babies. Vasopressin concentrations in the umbilical arterial blood of babies born after spontaneous delivery were remarkably high, as compared to all the other groups. Despite a wide range, between 5-2200 pg/ml, there was no correlation between the magnitude of vasopressin elevation and the severity of fetal asphyxia (Fig. 1). The present finding in part, confirms and expands previously observed increased vasopressin levels in the cord blood after spontaneous vaginal delivery. In addition, a lack of correlation between fetal asphyxia and the vasopressin levels suggests that these high levels may not be related to this form of stress.


Some psychological characteristics of prostitutes.

Ninety-five prostitutes, differentiated into five intra-occupational categories based on their method of operation, and an equal number of nonprostitute demographically matched controls, were interviewed and administered the WAIS Vocuabulary subtest, the MMPI, and the Rorschach. The data reveal that prostitutes on the upper end of the intra-occupational scale, such as call girls and those working in-house, are not significantly different from the nonprostitute controls. At the other end of the intra-occupational scale, street-walkers appear to be less mature and more dependent than their controls. Part-time prostitutes, such as housewives and drug dependent subjects, yield major indices of psychopathology.


The predicative ability of HABGT scales for a male delinquent population.

The Adience-Abience and the Psychopathology Scales of the HABGT were applied under pretreatment and posttreatment conditions to 120 13-15-year-old male delinquents. Comparison with other personality variables, prediction of recidivism, and analysis of mean scores on the two scales with the means of normal and disturbed children of comparable age were attempted. The delinquent  group was more ambient than normal children and was significantly higher in psychopathology than either normals or disturbed children. Significant correlations were obtained between Adience-Abience and Psychopathology and recidivism, although neither scale alone, nor both scales in combination, was high enough in prediction to warrant their use for individual predictive purposes. However, their utility in such programs as well as their construct validity were demonstrated.


Relevant MMPI norms for young adult Air Force trainees.

The Air Force Medical Evaluation Test (AFMET) research program utilized the MMPI in a psychological screening battery for basic trainees. T-scores based on the Adult Norms seemed excessively elevated. The norms for Minnesota Adolescents were tried for the 17-year-old airmen. MMPIs were given to entire squadrons not in the project, and the means and standard deviations were found to differ significantly from both earlier norms. These young adults differed in age, race, and education from the sample population of the Minnesota Adult Norms. T-conversion tables based on these new means and standard deviations were compiled.


MMPI cannot say scores: normative data and degree of profile distortion.

Few previous studies have investigated MMPI Cannot Say scores (the number of items people omit in completing the MMPI). Study 1 examined the frequency of occurrence of omitted items in three different populations. A significantly higher proportion of complete MMPI answer sheets (no omitted items) was found among job applicants than among two psychiatric groups, and the vast majority of test subjects in all three groups responded to all items. Study 2 investigated the degree of profile distortion introduced by randomly omitting various numbers of MMPI items from complete answer sheets. As more MMPI items were omitted, there was a progressive reduction in the elevation of the MMPI profile, but several different analyses failed to reveal a definite point at which the number of omitted items clearly became excessive. Changes in the profile's high-point pair were sometimes produced by numbers of omitted items previously considered to be expected in a "normal" MMPI record. This type of profile distortion could alter significantly the interpretation of a profile. Changes were therefore suggested in the T-score values for the Cannot Say scale given on the standard profile.


A comparison of four personality inventories.

The equivalence of personality constructs measured by four rationally devised inventories watested by means of a factor analytic approach. The tests were administered to large high school and college samples. Separate analysis of each inventory were followed by analysis of pooled scales representing each factor found in any inventory. Twelve dimensions were found to be common to two or more inventories and consistent across the two samples. The results indicate a convergence on a set of basic personality constructs measurable and equivalent in several inventories.


Conservatism, openness to experience and sample bias.

Two experiments were conducted to examine the relationship between conservatism and openness to experiences. In Study I, the responses of 64 males and 60 females to the Conservatism Scale and the Coan (1972) Experience Inventory were correlated. For the total sample, conservatism was significantly related to the total score of the Experience Inventory plus six of seven of the component scales. Study II examined the relationship between conservatism and the expressed willingness to volunteer for certain psychological experiments that were assumed to require more openness. Subjects were 91 males and 114 females from introductory psychology classes. High conservative subjects were less willing to volunteer for the experiments that required more openness as compared to low conservative subjects. These results were discussed in the context of volunteer bias in psychological research.


Anxiety and mood states in delinquent adolescents.

Studied the relationship between state-trait anxiety and  mood states in deliquents by giving the State-Trait Anxiety Inventory for Children (STAIC) (Spielberger, 1973) and the Profile of Mood States (POMS) (McNair, Lorr, & Droppleman, 1971) to 41 behavior problem adolescents who were residents of a facility for youthful offenders. Results indicated that males and females did not differ significantly. The A-State portion of the STAIC was correlated significantly with the Vigor-Activity and Anger-Hostility portions of the POMS as well as the Total Mood Disturbance index. On the other hand, the A-Trait portion of the STAIC was correlated significantly with the Depression-Dejection, the Tension-Anxiety, and the Fatigue-Inertia portions of the POMS as well as the Total Mood Disturbance index. Findings were discussed in terms of their relationship to previous research and in terms of the differences in conception of affective states presented by Spielberger (1973) and McNair et al. (1971).


Biographical, trait, and behavioral-sampling predictions of performance in a stressful life setting.

Biographical, trait, and behavioral-sampling predictors, when combined, yield a substantially and significantly larger prediction of performance, R = .72, in a natural setting than any of these approaches achieve separately (Rs, respectively, of .64, .44, and .42; all ps less than .01). A canonical correlational analysis designed to determine which predictors best predict which component of the multifaceted criterion suggests that traits best predict other traits, while specific past behaviors and learning experiences best predict specific future skilled performances. Personality assessment, which has been preoccupied with simple competitions between behavioral-sampling and trait approaches, might progress faster if it reformulated its task in a broader, more cooperative fashion.


Creative productivity, age, and stress: a biographical time-series analysis of 10 classical composers.

The determinants of creative productivity were specified in the form of six hypotheses. Using a multivariate cross-sectional time-series design with several controls, the lives and works of 10 classical composers were analyzed into consecutive 5-year age periods. Two independent measures of productivity were operationalized (works and themes), with each measure subdivided into major and minor compositions according to a citation criterion. It was consistently found across both productivity measures that (a) quality of productivity is a probabilistic consequence of productive quantity and (b) total productivity, while affected by age and physical illness, is otherwise free of external influences (viz., social reinforcement, biographical stress, war intensity, and internal disturbances). Due to the more selective nature of the thematic productivity measure, the criterion of total themes alone was affected by competition and a time-wise bias. The article closes with a brief discussion of the broad substantive utility of the methodological design.


What mediates the effect of mild erotica on annoyance and hostile behavior in males?

Male subjects were provoked or not provoked, exposed to photographs of (a) nonerotica, (b) nude females, or (c) couples engaged in sexual activities, and provided with an opportunity to express annoyance and to retaliate against their annoyer. Both annoyance and retaliatory behavior were measured. The excitatory potential, the involvement potential, and the hedonic valence of the nonerotic and erotic stimuli were also assessed. Provocation produced strong effects on all measures of annoyance and retaliatory behavior. In unprovoked subjects, erotica had no effect whatsoever on such behavior. Under conditions of provocation, reported annoyance in both erotica conditions was significantly less than in nonerotic condition. There was no corresponding differentiation in retaliatory behavior, however. The excitatory potential of the erotica employed, as measured in heart-rate and blood-pressure changes, proved to be minimal. No stimulus differences in involvement potential were found. The erotica were similarly pleasing. The nonerotica, in contrast, were conisdered boring. The findings are discussed in terms of various theoretical proposals concerning the relationship between erotica and aggression.


Microbiological turbidimetric methods: linearization of antibiotic and vitamin standard curves.

Procedures were devised to linearize the usually curved calibration lines for turbidimetric microbiological assays. Three new equations relating concentration of drug and turbidity are described; two are for antibiotic assays and one for vitamin assays. One equation is for antibiotic assays employing Klebsiella pneumoniae as the test organism. The accuracy of interpolation from the three equations was studied by means of appropriate mathematical models based on erthromycin, chlortetracycline (K. pneumoniae), and cyanocobalamin assays. The accuracy of the new expressions was significantly superior to those used previously, and they are of general applicability.


Skin as an active metabolizing barrier I: Theoretical analysis of topical bioavailability.

A model and explicit  equations were developed to be used in the experimental design and data evaluation of situations where simultaneous metabolism and transport of drugs occur in the skin. By treating the skin as a two-ply laminate composed of the stratum corneum and the viable epidermis, which contains most of the catabolic enzymes that might render a drug inactive by metabolism, equations were developed permitting the in vitro assessment of factors that may affect topical bioavailability in vivo. Two situations were investigated. In the first, the drug was placed on the dermis side of the diffusion cell and did not penerate the stratum corneum. In the second, the drug, placed on the epidermis side, penetrated the stratum corneum and then passed through the metabolizing epidermis. Expressions for determining the metabolic rate constant from experimental data along with concentration profiles and flux expressions are given both for the drug and its metabolite.


Role of carbonate in acid neutralization of aluminum hydroxide gel.

The role of carbonate in the acid neutralization of a carbonate-containing aluminum hydroxide gel was studied. The pH-stat neutralization reaction was comprised of three phases: an initial, immediately reacting phase; a slow, zero-order phase; and a terminal, fast zero-order phase. The evolution of carbon dioxide and the appearance of aluminum ions were monitored during neutralization. Acid neutralization is believed to occur predominantly at the aluminum-carbonate bond during the slow phase of neutralization. The reaction of structural carbonate disrupts the gel structure and increases the porosity and surface area of the gel. The diffusion of acid into the gel structure is facilitated and accelerates the neutralization rate, as seen in the final phase of the pH-stat titrigrams. The behavior of carbonate is probably responsible for the rapid and complete neutralization of acid generally observed with carbonate-containing aluminum hydroxide gel.


Surface tension lowering and dissolution rate of hydrocortisone from solid solutions of selected n-acyl esters of cholesterol.

The dissolution of hydrocortisone into simulated intestinal fluid from lipid delivery systems followed second-order kinetics. As the ratio of hydrocortisone to lipid was increased from 1:1 to 1:6, the dissolution rate decreased. Solvent deposition of solid solutions of hydrocortisone and lipid on lactose resulted in the enhancement of the dissolution rate. For the 1:1 hydrocortisone-lipid solid solutions, the rank order of the dissolution rate was hydrocortisone-cholesteryl stearate, hydrocortisone, hydrocortisone-cholesterol, hydrocortisone-cholesteryl acetate, hydrocortisone-cholesteryl palmitate, hydrocortisone-cholesteryl n-butyrate, hydrocortisone-cholesteryl laurate, and hydrocortisone-cholesteryl n-decylate. A direct correlation was found between the dissolution rate of hydrocortisone and the surface tension lowering of simulated intestinal fluid by the corticoid and various lipids.


Polyethylene glycol as a binder for tablets.

Polyethylene glycol 6000 was evaluated as a binder for the direct compression of 11 tablet formulations. Six formulations compressed quite well, and the resulting tablets were satisfactory in all respects. To evaluate stability, actual shelflife studies were considered more appropriate than the accelerated studies. After a shelflife of 3 years, five of the six formulations were stable. The ascorbic acid formulation was stable for up to 18 months.


Determination of diphenoxylate hydrochloride and atropine sulfate in solutions and tablets.

Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbersome and, in the case of solutions, inaccurate due to spectral interferences; the proposed methods offer substantial improvements in sensitivity, specificity, and speed. Results obtained by the USP and proposed methods are compared for several lots of commercial products. The accuracy and precision of the proposed methods are shown by standard recovery studies.


Synthesis and anticancer activity of novel cyclic N-hydroxyureas.

To overcome the disadvantages of hydroxyurea in anticancer therapy such as fast biotransformation and low potency, five cyclic N-hydroxyureas were synthesized. A new reaction was developed to prepare the desired products from the appropriate alkyl omega-haloalkylcarbamates with hydroxylamine. This reaction probably involves a two-step mechanism: nucleophilic substitution and intramolecular cyclization. The anticancer screening tests of these compounds were done both in vitro using tissue culture and in vivo. One compound, 1-hydroxy-1,3-diazacylohexan-2-one, had anticancer activity comparable to hydroxyurea both in vivo and in vitro.


ac Polarography for tetracycline analysis.

The electrode processes for the reduction of several tetracyclines by ac polarography were examined. In pH 4.0 Walpole acetic acid-acetate buffer, two main waves occurred; the first was quasireversible and the second was reversible. Results showed that the first wave can readily be used for quantitative work. The second wave would also be suitable provided that there was no interference from other electroreducible substances.


Evaluation of drug formulations using LD50 testing in mice.

The LD50 values were utilized to assess the relative rate of absorption of two very poorly soluble drugs. Formulations of these drugs were studied by micronization; addition of surfactant, alkaline or buffering agents, and/or bile salts; coprecipitation; melt or fusion techniques; or granulation with hydrophilic agents. Differences in toxicities were demonstrated from formulations compared to pure drugs by the LD50 method. This study shows that the LD50 is a practical, rapid method of achieving comparative evaluations of drug formulations.


Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-chemical-ionization mass spectrometry.

The (+)-,(-)-, and (+/-)-2H5-methadones, which contained five deuterium atoms in one aromatic ring, were synthesized for use in clinical pharmacological studies and as internal standards. GLC-chemical-ionization mass spectrometry was used to determine plasma and urinary methadone levels by an inverse isotope dilution assay. Plasma drug levels could be determined to 10 pmoles/ml, and urine levels could be measured to 5 pmoles/ml. Plasma  methadone levels were examined in several patients undergoing methadone maintenance therapy. These levels generally ranged between 100 and 400 ng/ml (320-1300 pmoles/ml) after an average oral dose of 1 mg/kg/day. The methadone half-life was 28.8 +/- 4.8 hr.


Piperidine derivatives: synthesis of potential analgesics in 3-substituted 4-phenylpiperidine series.

The syntheses of 1-methyl-3-(3-hydroxy-3-phenylpropyl)-4-phenyl-4-piperidinol and 1-methyl-3(3-hydroxy-3-phenylpropyl)-4-phenyl-4-propanoyloxypiperidine are described. Preliminary pharmacological testing showed these compounds to be weakly active in the writhing  test.


Synthesis and structure-activity relationships of selected isomeric oxime O-ethers as anticholinergic agents.

A series of isomeric (Z)-and (E)-oxime O-beta-dimethylaminoethyl ether methylhalide derivatives was synthesized, and their (Z)-and (E)-assignments were made on the basis of chemical and spectral data. The respective (Z)-and (E)-isomers were evaluated as anticholinergic agents on the rat ileum. The antimuscarinic potencies of the respective (Z)-and (E)-isomers were compared to determine the effect upon potency of this type of geometric  isomerism. Three general structure-activity  relationships and discernible among the synthesized compounds: (a) among oxime O-ethers derived from aromatic aldehydes, the higher potency consistently resides in the isomer where the aryl substituent is (E) to the ammonium ether substituent; (B) among oxime O-ethers derived from diaryl ketones, the (Z)-and (E)-isomers are approximately equipotent; and (c) oxime O-ethers derived from diaryl ketones are the most potent of the synthesized compounds.


N-Glucopyranosyl-5-aralkylidenerhodanines: synthesis and antibacterial and antiviral activities.

A series N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)-5-aralkylidenerhodanines was synthesized, and the acetyl groups were removed to give N-beta-D-glucopyranosyl-5-aralkylidenerhodanies  without cleavage of the rhodanine ring by means of acid hydrolysis. Alkaline hydrolysis  with ammonia in methanol resulted in cleavage to N-glucosylthiourea, providing evidence for N-glycoside formation. A number of the rhodanine derivatives, especially those with nitro or chloro groups in the aromatic ring, showed antibacterial activity. N-beta-D-Glucopyranosyl-5-(4-nitrobenzylidene) rhodanine showed antiviral activity by inhibition of viral RNA synthesis. Some effect on blood sugar levels also was observed with several rhodanines.


Effects of polyelectrolytes on drug transport II: permeation.

The permeation rate of salicylate across a dialysis membrane was studied in the presence of various types of carboxymethylcellulose. The presence of the polymer in the salicylate solution increased the permeation rate of salicylate. The data were analyzed with a diffusional model in which the viscosity and charge effects were evaluated separately.


Metoclopramide metabolism and determination by high-pressure liquid chromatography.

A high-pressure liquid chromatographic method suitable for determining plasma metoclopramide levels at normal (10-20 mg) doses is  described. Eight metabolites as well as metclopramide were isolated and identified in rat, dog. and human urine. The only common metabolite in these species is 2-[(4-amino-5-chloro-2-methoxybenzoyl)-amino] acetic acid. N-Deethylation is a major pathway for metoclopramide metabolism in the lower animals but not in humans. Metoclopramide is excreted mainly unchanged or as its conjugates by humans.


High-speed liquid chromatographic analysis of dapsone and related compounds.

A nonaqueous solvent absorptive support system and an aqueous solvent reversed-phase support liquid chromatographic system for analysis of dapsone and related compounds were investigated. The absorptive support system was more suitable for analysis of dapsone in raw materials, formulations, and tissue residues. The suitability was judged by the relative selectivity, efficiency, precision, and sensitivity of the systems. The adsorptive support system was used for the analysis of trace amounts of raw material impurities and dapsone metabolites. Coupling fluorometric detection to the chromatographic system yielded a 10-pg on-column detection limit for dapsone; the UV detection limit was 250 pg.


Preparation and skin-photosensitizing activity of substituted psoralens.

8-Monosubstituted and 5,8-disubstituted psoralen derivatives were prepared, and their skin-photosensitizing activity was evaluated. The results were correlated in terms of  molecular configuration, and 8-allyloxypsoralen can be considered was a new agent of potent photodynamic activity.


High-speed liquid chromatographic determination of pilocarpine in pharmaceutical dosage forms.

A specific method for the direct determination of pilocarpine in aqueous pharmaceuticals in the presence of decomposition products, methylcellulose, and other ingredients usually present in pharmaceuticals is described. The method involves separation by high-speed liquid chromatography using, in series, octadecylsilane bonded to silica and cyanopropylsilane bonded to silica columns and a tetrahydrofuran-pH 9.2 borate buffer (3:7) eluant. Quantitation is achieved by monitoring the absorbance of the effluent at 254 nm and using a pyridine internal standard and a calibration curve prepared from known concentrations of pilocarpine nitrate. The reproducibility of the retention time and peak area was better than 2.0%.


Alkaloids of Nelumbo lutea (Wild.) pers. (Nymphaeaceae)

A phytochemical investigation of an alcoholic extract of the petioles of Nelumbo lutea resulted in the identification  of the alkaloids N-methylasimilobine, anonaine, and roemerine. The alkaloids nuciferine, armepavine, N-nornuciferine, and N-norarmepavine, previously previously reported in  the whole plant, were also identified.


GLC microanalyses of phenacetin and acetaminophen plasma levels.

A GLC method utilizing a flame-ionization detector is described for the simultaneous analysis of acetaminophen and phenacetin in plasma. p-Bromoacetanilide is used as an internal standard. The drugs are extracted with ether from plasma diluted with 1 M phosphate buffer (pH 7.4). The ether extract is evaporated to dryness under nitrogen, and the residue is dissolved in 300 microliter of ethyl acetate. The ethyl acetate is transferred to a microcentrifuge tube (0.4 ml), and the sample is evaporated in a vacuum centrifuge. Then  the residue is redissolved in 0.2 M trimethylanilinium hydroxide in methanol for GLC analysis. Extraction  efficiency of added phenacetin and acetaminophen in  plasma at concentrations of 1-10 microgram/ml was complete, and the limit of detection in plasma was less than 0.1 microgram.


Molecular connectivity and retention indexes.

The molecular connectivity indexes, chi, of some alcohols, ethers, esters, and ketones did not correlate very well with their retention volumes in some GLC systems. It was concluded that the utility of chi for the prediction of biological activities could prove rather limited.


Fluorometric determination of methyldopa in biological fluids.

A fluorometric method for the analysis of methyldopa, based on the formation of a fluorophore after oxidation and rearrangement, is described. The drug  is isolated from biological fluids by adsorption on alumina and elution with an organic solvent. Fluoresence is linear from 0.1 to 1.5 microgram of methyldopa/ml. The assay has a lower limit of sensitivity of 100 ng/ml and is suitable for pharmacokinetic studies following therapeutic doses in animals and humans.


GLC determination of N,N-dimethylaniline in penicillins.

A reliable GLC procedure was developed for the determination of residual N,N-dimethylaniline as a contaminant in ampicillin commerical samples from various sources. The procedure was similarly applied to other penicillins and cephalosporins. The method involves dissolution of the sample in aqueous alkali, extraction of the organic base with cyclohexane containing naphthalene as an internal standard, and injection into gas chromatograph with a phenyl methyl silicone column. Levels of 0.1 ppm of dimethylaniline were easily measured with a coefficient of variation less than 10%, and recoveries from spiked samples exceeded 99%.


Aging of tablets made with dibasic calcium phosphate dihydrate as matrix.

The aging of direct compression tablets made using dibasic calcium phosphate dihydrate as the tablet matrix was investigated over 16 weeks. The formula included 6% amaranth as a dye tracer. Two sets of stress storage conditions were used: 25 degrees and 50% relative humidity and 45 degrees and 75% relative humidity. Tablets were evaluated periodically by visual inspection; determination of the weight of 10 separate tablets, the size of 10 tablets measured by a micrometer screw gauge, and the hardness of 10 tablets as indicated by a Strong-Cobb hardness tester; the USP disintegration time test; and the USP dissolution test. Tablets stored at 25 degrees and 50% relative humidity showed an  approximately linear increase in disintegration and dissolution time over 16 weeks with no other significant changes. Storage at 45 degrees and 75% relative himidity resulted in significant changes in most measured parameters; tablets showed blotching, substantial  weight loss, and complex changes in disintegration  and dissolution. The changes at elevated temperatures are related to loss of water of hydration; changes at 25 degrees must be due to other causes.


Comparative drug adsorption by activated charcoal.

Comparative in vitro studies were carried out to determine the adsorption characteristics of 12 drugs on activated charcoal. At pH 1.3 and 37 degrees, the adsorption capacity of activated charcoal (milligrams per gram of charcoal) was: aspirin, 262; glutethimide, 252; methaqualone, 179; chlordiazepoxide, 157; propoxyphene napsylate, 137; diazepam, 136; amitriptyline, 133; propoxyphene hydrochloride, 127; secobarbital, 124, pentobarbital, 103; phenobarbital, 70; and amobarbital, 51. The adsorption of the weak acids was most markedly decreased at pH 10.8. In patients, actual drug adsorption probably is lower than these maxima because of the presence of mucus, bile salts, and other drugs. In patients investing large amounts of poorly adsorbed drugs, activated charcoal would not be helpful.


Plasma concentrations and bioavailability of clofibric acid from its calcium salt in humans.

The bioavailability of clofibric acid from formulations containing calcium clofibrate along and mixed with calcium carbonate (1:1 w/w) was compared to that from a standard clofibrate formulation in a crossover study in 12 human subjects. The 95% confidence intervals of bioavailability differences were such that  they were unlikely to be detected in  clinical practice; all three formulations may be considered bioequivalent, although the bioavailability rate was probably greater from the formulation containing calcium clofibrate alone. Peaks of mean concentrations of 80 +/- 13,67 +/- 16, and 64 +/- 18 microgram/ml +/- SD occurred after administration of 853 mg of clofibric acid calcium salt alone, 809 mg of clofibric acid calcium salt mixed with calcium carbonate, and 885 mg of clofibrate, respectively; mean concentrations declined from peak levels with half-lives of 15-17 hr.


Determination of anthranilic acid in plasma.

A simple, specific GLC method was developed for the determination of anthranilic acid in plasma. This method is based on extraction from a carefully controlled buffer followed by removal of solvent, silyation, and detection in the gas chromatograph. The procedure is quantitative in the 2-10 microgram/ml range.


Detection of penicillin G and ampicillin as contaminants in tetracyclines and penicillamine.

A method was developed to detect residual levels of ampicillin and penicillin G in various tetracyclines and penicillamine. Residues are detected by reversed-phase TLC followed by bioautography. The directness of the techniques makes this method a good means of detecting residual contaminants in drugs.


Interactions of indomethacin with lysosomes and proteins.

The stabilizing action of indomethacin on lysosomes and protein in vivtro was studied. The magnitude of the stabilizing action on lysosomes was greater than that of aspirin or oxyphenbutazone, similar to that of phenylbutazone, but less than that of prednisolone. The stabilizing action of indomethacin on lysosomes possibly may contribute to its anti-inflammatory  properties.


Effect of pentazocine on pressor responses of epinephrine and levarterenol.

In rats anesthetized with pentobarbital, pentazocine potentiated the pressor response of two exogenous amines, epinephrine and levarterenol. Although the mechanism for the pentazocine-induced potentiation of the pressor amines has not been proven, it is speculated that pentazocine may increase the blood pressure response of certain amines by interacting with the sympathetic nervous system.


Synthesis and hydrolysis of fluorene-9-spiro-2'-(N-aryl-3' ,3'-dichloroaziridines)

The synthesis of eight fluorene-9-spiro-2'-(N-aryl-3' ,3'-dichloroaziridines) was achieved via the reaction of dichlorocarbene with the  appropriately substituted N-fluorenylideneanilines. Hydrolysis of the spirofluorenes afforded the corresponding 9-chlorofluorene-9-carboxanilides in excellent yields.


TLC sensitivity of six modifications of Dragendorff's reagent.

The relative sensitivities of six modifications of Dragendorff's reagent were measured on TLC plates  by spectrodensitometry, using compounds containing specific functional groups. A correlation between the structures of the compounds reactive to Dragendorff's reagents and the sensitivities of the reagents was made. Explanations for the variations in sensitivities between different modifications of Dragendorff's reagent are given.


Sodium nitroprusside-induced hypothermia in mice.

The hypothermic response following sublethal doses (1.25, 2.5, and 5 mg/kg) of sodium nitroprusside  was investigated in mice. The magnitude and duration of rectal temperature depression were shown to be dose related. Oral administration of nitroprusside (5 mg/kg) failed to alter rectal temperature significantly; subcutaneous,  intraperitoneal,  intravenous, and intracerebral injections at the same dosage level caused respective drops of 3.61, 3.65, 6.44, and 3.48 degrees. The degree of rectal temperature depression following nitroprusside (5 mg/kg ip) was dependent upon the ambient temperature. The time course of the effect of  nitroprusside (5 mg/kg ip) on tail temperature was noted. A transient rise in tail temperature, which coincided with the onset of rectal temperature depression,  was attributed to the vasodilatory effect of the drug. Tail temperature depression occurred at the peak and throughout the remainder of the rectal temperature response, suggesting that nitroprusside may decrease heat production. Body temperature depression via intracerebral administration, as well as pronounced sedation following nitroprusside injection, suggests a central component to the thermolytic response.


Diffusion of oxygen at the endothelial surface of the rabbit cornea.

1. An in vitro investigation was made to determine the oxygen tension level required at the endothelial surface of rabbit cornea to produce a net oxygen flux into the cornea across this surface when the epithelial surface was exposed to air. 2. The experimental design was based on a mathematical model which showed that the direction of oxygen flux measured in an agar layer adjacent to the endothelium was the same as the direction of oxygen flux across the endothelial surface. 3. From micro-electrode measurements of oxygen tension in the agar layer, it was found that an oxygen tension greater than 102 mmHg at the endothelial surface was required tocause a net flux of oxygen into the cornea. 4. Comparing this result to the in vivo situation,it was concluded that all layers of the rabbit cornea receive oxygen from the atmosphere under open eye conditions.


Post-tetanic potentiation, habituation and facilitation of synaptic potentials in reticulospinal neurones of lamprey.

1. Synaptic potentials evoked by electrical stimulation of cranial nerves were recorded in giant reticulospinal neurones (Müller cells) of lamprey. A variety of patterns of stimulation was employed to explore further the functional properties of the pathways intervening between the cranial nerve fibres and Müller cells.2. Simultaneous low intensity stimulation of two different cranial nerves produced excitatory short-latency synaptic potentials whose amplitudes summed linearly.3. Tetanic (10/sec) stimulation of a cranial nerve depressed the evoked short-latency synaptic response, but following the tetanus the synaptic response was potentiated above control amplitude for several minutes. Tetanic stimulation of one cranial nerve had no effect upon the synaptic responses evoked by stimulation of other cranial nerves.4. Low-frequency stimulation (1/sec to 1/20 sec) of a cranial nerve produced a progressive decrease in the amplitude of the evoked short-latency synaptic response. This phenomenon was termed synaptic habituation because its characteristics were functionally similar to behavioural habituation in animals.5. Habituation of the synaptic response to stimulation of one cranial nerve had no effect on the synaptic responses produced by stimulation of other cranial nerves.6. Synaptic afterdischarges lasting from several seconds to several minutes were recorded in Müller cells. They occurred both spontaneously and in response to strong electrical stimulation of cranial nerves. For several minutes following an afterdischarge the amplitudes of short-latency synaptic potentials produced by stimulation of any one of the cranial nerves were increased as much as twofold. This facilitation occurred equally well whether the short-latency synaptic responses had been habituated or not.7. A theoretical cell-wiring diagram is proposed to account for the properties of short-latency evoked synaptic responses and synaptic afterdischarges and for the facilitation of short-latency responses by afterdischarges.


A potassium contribution to the response of the barnacle photoreceptor.

1. Intracellular recording from photoreceptors in the lateral eye of the barnacle show a brief negative-going 'dip' shortly after the onset of the late receptor potential. This phase can sometimes result in a hyperpolarization relative to the resting membrane potential. 2. The dip is prominent in light-adapted cells and is reduced by dark-adaptation. Low extracellular Ca2+ also reduces it. 3. The amplitude of the dip changes inversely with the K+ concentration in the saline. 4. The amplitude of the dip depends on the membrane potential, with a reversal potential near - 80 mV. 5. K+ blocking agents such as quinine and quinidine reduce or abolish the dip. 6. These observations indicate that the dip is due to a brief increase in K+ conductance which may be dependent on an influx of Ca ions. The fast decay of this phase may be brought about by a rapid uptake of Ca2+ by an intracellular mechanism.


Membrane properties and conduction velocity in sensory neurones following central or peripheral axotomy.

1. The properties of dorsal root ganglion cells in the lumbosacral segments were examined with intracellular electrodes about 3 weeks after section of the central (dorsal roots) or peripheral processes in the cat.2. Chronic section of the peripheral nerve in the hind limb resulted in a reduction in conduction velocity of both the central and peripheral processes of sensory neurones.3. Sensory neurones arising from the triceps surae and plantaris muscles were subject to ;disuse' conditions for about 3 weeks by section of the ventral roots combined with severance of the Achilles tendon. Under such conditions, the central and peripheral conduction velocities of these sensory neurones tended to decrease, but the decrease was significantly less than that following peripheral nerve section.4. Chronic section of the dorsal roots produced no significant changes in conduction velocity of the central processes of muscle sensory neurones but caused a significant increase in the peripheral conduction velocity.5. The only electrophysiological property of dorsal root ganglion cells which altered following axotomy was the time-dependent membrane rectification in response to hyperpolarizing current pulses. The rectification characteristics were modified by chronic section of the peripheral nerve but not by chronic section of the dorsal root.6. It is concluded that injuries in nerve fibres per se do not necessarily result in a decrease of their conduction velocity and that a decrease in their conduction velocity is associated with changes in the properties of the cell bodies.7. It is suggested that a decrease in conduction velocity following nerve section may require the participation of changes in the neurone cell body.


Close relation between TEA responses and Ca-dependent membrane phenomena of four identified leech neurones.

1. Tetraethylammonium chloride (TEA) was applied to four kinds of identified neurones in leech segmental ganglia, namely, the sensory cells responding to touch (T), pressure (P) and noxious (N) stimuli and the Retzius cell (R).2. TEA prolonged the action potentials of these cells to characteristically different degrees, in the order R > N > P > T, regardless of exposure time. This result was the same whether TEA was presented to the whole ganglion via the bathing fluid or injected iontophoretically into the soma of the cell under study.3. TEA in Na-free solution caused the behaviour of the N cell membrane to be dominated by a Ca-dependent, Mn-blockable event identical in every respect except smaller size to the previously described behaviour of the R cell under the same conditions. The P cell displayed a still smaller event of the same kind, but none was detectable in the T cell.4. In the absence of both TEA and Na, when Ca was the only extra-cellular cation available to carry current, active membrane responses to depolarization were present in the R cell (previous study) and the N cell; such responses were minimal in the P cell and absent from the T cell.5. Differences among the four cells in density of a divalent cation conductance mechanism are the simplest explanation for these observations, though a more complex explanation based on multiple, pharmacologically distinct K conductances is not excluded by our data.


The effects of external sodium substitution on cell sodium and potassium in vascular smooth muscle.

1. The entry of Li into the vascular smooth muscle cells of the rat tail artery follows first-order kinetics with a rate constant of approximately 1.3 hr(-1) at 10 mM-[Li](o). The rate constant decreases gradually to ca. 0.5 hr(-1) when the [Li](o)/[Na](o) ratio is increased.2. Replacement of Na with Li over the range of [Li](o) from 1 to 115 mM, accomplished at constant ionic strength and osmolarity of the bathing solution, produces changes in cell Na and K without apparent change in cell water. At equilibrium, cell Li increases in linear proportion to [Li](o), at a ratio of 2:1 throughout the range. The increase in cell Li is associated with inverse falls in both cell K and Na such that the ratio of cell K to cell Na remains constant at ca. 10:1 throughout.3. The changes in the ionic contents, induced by equilibration of the tissue with a Na-free, Li-substituted solution, are reversible.4. Replacement of Na with sucrose over the range of 40-115 mM results, at equilibrium, in a linear fall in cell Na without conspicuous change in cell K. A constant portion of the cell Na, ca. 10 m-mole/kg dry wt., does not participate in this exchange.5. At equilibrium, reductions in [Na](o) are reflected in corresponding reductions in apparent [Na](i) such that the [Na](o)/[Na](i) ratio remains constant.


Short circuit current and total conductance measurements on rat ileum.

1. Short circuit current and total conductance measurements were made on preparations of rat terminal ileum, using either the intact tissue or the isolated epithelium.2. The effects of D-glucose, 3-O-methyl-D-glucose, and 3-deoxy-3-fluor-D-glucose, added in suitable concentrations to the external bathing medium, were studied.3. An increase in both short circuit current and total conductance was detected when these sugars were used. It was possible to determine a linear relationship between the two variables and to study the kinetics of the interaction of glucose and 3-O-methyl-D-glucose with the sodium sugar carrier by using increasing concentrations of these substances.4. The increases in short circuit current and total conductance were also verified in isolated epithelium.5. Phlorizin, or the withdrawal of glucose, reversed the increase in short circuit current, but the total conductance remained unchanged.6. Increasing concentrations of 2-deoxy-D-glucose added to the mucosal bathing medium caused a decrease in short circuit current without changing the total conductance, either in preparations of intact ileum or in isolated epithelium.7. The meaning of these variations in the electrical parameters of the preparations is discussed.


The force of contraction of the human ciliary muscle during accommodation.

1. Apparatus has been designed to alter the shape of the human lens by tensile forces applied to the zonular fibres indirectly through the ciliary body. The changes in dioptric power of the lens for monochromatic sodium light were measured at the same time. Simultaneous serial photography, and direct measurement enabled one to relate a change in shape of the lens to the change in dioptric power. Subsequently, the same lens was isolated and spun around its antero-posterior polar axis and high speed photography recorded its changing profile.2. By comparing the changes in lens profile due to zonular tension and centrifugal force respectively, the force developed in the zonule for a given change in the shape of the lens could be calculated. Changes in dioptric power associated with those of shape can thus be related directly to the force of contraction of the ciliary muscle necessary to reduce the initial tension of the zonule in the unaccommodated state.3. The force of contraction of the ciliary muscle as measured by radial force exerted through the zonule and the change in dioptric power of the lens were not linearly related. The relationship is more exactly expressed by the equation [Formula: see text] where D = amplitude of accommodation in dioptres (m(-1)), F(CB) = force of contraction of the ciliary muscle as measured by changes in tension of the zonule (N), K(df) = dioptric force coefficient and is constant for a given age (m(-1)N(-(1/2)) x 10(2.5)). This coefficient is 0.41 at 15 yr and 0.07 at 45 yr of age.4. In youth for maximum accommodation (10-12 D) the force is approximately 1.0 x 10(-2) N while to produce sufficient accommodation for near vision (3.5 D) the force is less than 0.05 x 10(-2) N.5. After the age of 30 yr the force of contraction of the ciliary muscle necessary to produce maximum accommodation rises steadily to about 50 yr of age and thereafter probably falls slightly. At about 50 yr of age the ciliary muscle is some 50% more powerful than in youth.6. Even if hypertrophy of the muscle did not occur the amplitude of accommodation would be reduced at the most by only 0.8 D of that observed at the onset of presbyopia.


Effects of innervation on acetylcholine sensitivity of developing muscle in vitro.

1. Chick embryo skeletal muscle fibres were grown in culture. The acetylcholine (AACh) sensitivity of non-innervated fibres was compared with that of fibres innervated in vitro by chick embryo ciliary ganglion neurones. 2. The general pattern of ACh sensitivity was unchanged by innervation: ACh hot spots were superimposed on a background of uniform ACh sensitivity. 3. Quantitative comparisons revealed two differences between non-innervated and innervated fibres. First, hot spots were encountered about one third more often on innervated fibres. Secondly, about one-third of the hot spots on innervated fibres had significantly higher ACh sensitivities than the remainder, which were similar to those on control fibres. 4. Apossible explanation of these results is that nerves which form synapses induce the appearanceof end-plates which have higher ACh sensitivities than the pre-existing ACh hot spots.


Physiological and anatomical characteristics of reticulospinalneurones in lamprey.

1. Intracellular records were obtained from giant reticulospinal cells (Müller cells) in the brain of adult lamprey. The cells had maximum resting potentials of -80 mV and action potentials with overshoots of 30 mV. Input resistances varied from 2 to 8 MOmega.2. Individual spontaneous excitatory and inhibitory synaptic potentials (e.p.s.p.s and i.p.s.p.s) were observed, as well as occasional high frequency bursts of excitatory potentials. Much of the spontaneous synaptic activity could be eliminated by elevating the Ca(2+) concentration in the bathing solution to 10-15 mM, suggesting that the synaptic potentials were due to spike activity in elements presynaptic to Müller cells.3. Electrical stimulation of cranial nerves produced synaptic responses in Müller cells. Ipsilateral vestibular nerve stimulation produced i.p.s.p.s; contralateral stimulation, e.p.s.p.s. Stimulation of either optic nerve produced mixed synaptic responses with e.p.s.p.s dominating in cells with large resting potentials. Trigeminal nerve stimulation produced mixed responses. Olfactory nerve stimulation produced excitation. Spinal cord stimulation produced e.p.s.p.s and i.p.s.p.s, the dominant effect being inhibition.4. In favourable preparations strong electrical stimulation of cranial nerves produced afterdisharges in Müller cells, lasting from a few seconds after stimulation of the olfactory and vestibular nerves to as long as several minutes after optic, trigeminal or spinal cord stimulation.5. Natural stimulation of tactile, visual and vestibular receptors resulted in synaptic responses similar to those produced by electrical stimulation of the cranial nerves. Fish odour applied to the olfactory mucosa produced no response.6. Iontophoretic application of L-glutamate to Müller cells produced depolarization accompanied by a decrease in input resistance. In addition, glutamate produced bursts of inhibitory and excitatory synaptic potentials, presumably by depolarizing excitatory or inhibitory nerve terminals or nearby cell bodies.7. Iontophoretic application of gamma-aminobutyric acid (GABA) resulted in a slight hyperpolarization, accompanied by a large reduction in input resistance. The reversal point both of the hyperpolarizations and of the spontaneous inhibitory post-synaptic potentials was about 6 mV greater than the resting potential.8. There were two types of synaptic ending on Müller cell bodies, one type containing round vesicles and the other containing ellipsoidal vesicles. These terminals were intermixed over the surface of the cell bodies and dendrites with no readily apparent segregation.9. Intracellular records from the spinal axons of Müller cells during electrical stimulation of cranial nerves and spinal cord showed, in addition to the normal propagating action potential activity which normally originates in the cell bodies, depolarizing, hyperpolarizing and biphasic evoked potentials. These membrane responses were grossly similar in appearance to synaptic potentials except that the large depolarizing potentials had unusually long decay times. The physiological basis of these potentials remains unclear.10. Electron microscopic examination showed very few synaptic endings afferent to Müller axons, a finding in contrast to the abundance of synaptic-like potentials recorded. However, the occasional synapses afferent to Müller axons were invariably located near an efferent synaptic region of the axon itself. This raises the possibility that a very limited number of synaptic regions of Müller axons may be subject to presynaptic modulation of transmitter release.11. The observations reported here support the idea that Müller cells in lamprey are an important motor outflow from the brain and serve to coordinate the lamprey's trunk responses to external sensory stimulation.


Responses of single units in cat visual cortex to moving bars of light as a function of bar length.

1. The responses of single units in the cat's primary visual cortex to moving bars have been examined quantitatively as a function of bar length.2. For about half the cells studied, very long bars evoked weaker responses than short bars, implying that there were inhibitory regions flanking the receptive field centre. In another quarter of the cell sample, there was evidence of flanking regions which were facilitatory in effect.3. The strength of the flanking regions was found to vary from cell to cell and there was no sudden transition between cells which were ;hyper-complex' and those which were not.4. Within the central region of the receptive field, the responses of most (but not all) cells increased with bar length. About half the cells responded to very short bars or spots of light, but about one in six would not respond at all to short bars.5. Correlations were sought between the properties of cells as simple or complex, their responsiveness to moving spots of light, the size of their receptive field centre and the polarity, strength and size of their receptive field flanks. Simple and complex cells with small receptive fields were more likely to respond well to spots, and to have strong inhibitory flanks.6. Correlations were also sought between the above properties and several other parameters of cell behaviour. Cells with strong inhibitory flanks were found to be more broadly tuned for orientation. Individual cells were also more broadly tuned for the orientation of short bars than of long bars.7. Evidence was obtained that spatial summation can be linear or non-linear for different cells.


Localization of calcium channels in Paramecium caudatum.

1. Electrical recordings from Paramecium caudatum were made after removal of the cilia with chloral hydrate and during ciliary regrowth to study the electrical properties of that portion of the surface membrane enclosing the ciliary axoneme. 2. Removal of the somatic cilia (a 50% reduction in membrane surface area) results in an almost complete elimination of the regenerative Ca response, all-or-none Ba2+ spike, and delayed rectification. 3. A twofold increase in input resistance resulted from the 50% reduction in membrane surface area. 4. The electrical properties remained unchanged, despite prolonged exposure to the chloral hydrate, until the cilia were mechanically removed. 5. Restoration of the Ca response accompanied ciliary regrowth, so that complete excitability returns when the cilia regain their original lengths. 6. It is concluded that the voltage-sensitive Ca channels are localized to that portion of surface membrane surrounding the cilia. 7. Measurements of membrane constants before and after deciliation and estimations of the cable constants of a single cilium suggest that the cilia of Paramecium may be fully isopotential along their length and with the major cell compartment.


Brain stem stimulation and the acetylcholine-evoked inhibition of neurones in the feline nucleus reticularis thalami.

1. In cats anaesthetized with halothane and nitrous oxide, the responses to iontophoretically applied acetylcholine (ACh) and to high-frequency stimulation of the mid-brain reticular formation (MRF) were tested on spontaneously active neurones in the nucleus reticularis thalami and underlying ventrobasal complex.2. The initial response to MRF stimulation of 90% of the ACh-inhibited neurones found in the region of the dorsolateral nucleus reticularis was an inhibition. Conversely, the initial response of 82% of the ACh-excited neurones in the ventrobasal complex was an excitation. Neurones in the rostral pole of the nucleus reticularis were inhibited by both ACh and RMF stimulation.3. The mean latency (and s.e. of mean) for the MRF-evoked inhibition was 13.7 +/- 3.2 ms (n = 42) and that for the MRF-evoked excitation, 44.1 +/- 4.2 ms (n = 35).4. The ACh-evoked inhibitions were blocked by iontophoretic atropine, in doses that did not block amino acid-evoked inhibition. In twenty-four ACh-inhibited neurones the effect of iontophoretic atropine was tested on MRF-evoked inhibition. In all twenty-four neurones atropine had no effect on the early phase of MRF-evoked inhibition but weakly antagonized the late phase of inhibition in nine of fourteen neurones.5. Interspike-interval histograms showed that the firing pattern of neurones in the nucleus reticularis was characterized by periods of prolonged, high-frequency bursting. Both the ACh-evoked inhibitions and the late phase of MRF-evoked inhibitions were accompanied by an increased burst activity. In contrast, iontophoretic atropine tended to suppress burst activity.6. The possibility is discussed that electrical stimulation of the MRF activates an inhibitory cholinergic projection to the nucleus reticularis. Since neurones of the nucleus reticularis have been shown to inhibit thalamic relay cells, activation of this inhibitory pathway may play a role in MRF-evoked facilitation of thalamo-cortical relay transmission and the associated electrocortical desynchronization.


Active chloride transport in the in vitro opercular skin of a teleost (Fundulus heteroclitus), a gill-like epithelium rich in chloride cells.

1. The opercular epithelium lining the inside of the gill chamber of the killifish, Fundulus heteroclitus, contains Cl(-) cells, identical in fine structure to gill Cl(-) cells, at the high density of 4 x 10(5) cells/cm(2). This epithelium can be isolated, mounted in a Lucite chamber, and its ion transport properties studied with the short-circuit current technique.2. The isolated opercular epithelia of seawater-adapted fish, when bathed on both sides with Ringer and gassed with 100% O(2), displayed a mean short-circuit current of 136.5 +/- 11.1 muA/cm(2), a mean transepithelial potential difference of 18.7 +/- 1.2 mV (blood side positive), and a mean transepithelial d.c. resistance of 173.7 +/- 12.1 Omega.cm(2) (mean +/- S.E. of mean; n = 64).3. The transepithelial potential difference across the opercular epithelia of seawater-adapted fish was dependent on both Na(+) and Cl(-) in the bathing solutions and increased linearly with increasing Cl(-) concentrations with a slope of 28.3 +/- 2.1 mV/tenfold concentration change. The short-circuit current was Na(+) dependent and increased linearly with increasing Cl(-) concentrations with no evidence of saturation kinetics below 142.5 m-equiv/l.4. When the short-circuited epithelia of seawater-adapted fish, bathed on both sides with Ringer, was gassed with 100% O(2) the mean Cl(-) blood side to seawater side flux was 211.7 +/- 27.1 muA/cm(2) and the mean Cl(-) seawater side to blood side flux was 48.9 +/- 10.0 muA/cm(2). This resulted in a net Cl(-) blood side to seawater side flux of 162.8 muA/cm(2) which was not statistically different (P > 0.70) from the mean short-circuit current of 158.6 +/- 16.3 muA/cm(2) for these flux studies. The mean Na(+) blood side to seawater side flux was 32.2 +/- 3.3 muA/cm(2) and the mean Na(+) seawater side to blood side flux was 34.8 +/- 4.1 muA/cm(2), resulting in no significant (P > 0.20) net flux of this cation. Similar results were obtained with short-circuited epithelia of seawater-adapted fish when bathed on both sides with Ringer and gassed with 95% O(2)/5% CO(2).5. Ouabain (10(-5)M), furosemide (10(-3)M), thiocyanate (10(-2)M), adrenaline (10(-6)M), and anoxia (100% N(2)) decreased the short-circuit current 92.7, 85.0, 45.3, 62.6, and 83.3% respectively. Theophylline (10(-4)M) stimulated the short-circuit current 54.9%. Increasing the HCO(3) (-) concentration in the bathing solutions had a stimulatory effect on the short-circuit current and the potential difference across epithelia from seawater-adapted fish.6. The opercular epithelia of freshwater-adapted F. heteroclitus, when bathed on both sides with Ringer, displayed a mean short-circuit current of 94.1 +/- 10.4 muA/cm(2), a mean transepithelial potential difference of 14.8 +/- 1.9 mV (blood side positive), and a mean d.c. resistance of 169.0 +/- 14.0 Omega.cm(2) (mean +/- S.E. of mean; n = 20). Isotope flux studies across these short-circuited epithelia revealed a net Cl(-) blood side to freshwater side flux of 95.2 +/- 16.1 muA/cm(2) and no significant net flux of Na(+).7. The opercular epithelia of 200% seawater-adapted F. heteroclitus, when bathed on both sides with Ringer, displayed a mean short-circuit current of 33.5 +/- 8.5 muA/cm(2), a mean transepithelial potential difference of 10.5 +/- 2.5 mV (blood side positive), and a mean transepithelial d.c. resistance of 440.7 +/- 62.6 Omega.cm(2) (mean +/- S.E. of mean n = 18). Isotope flux studies across these short-circuited epithelia revealed a net Cl(-) blood side to seawater side flux of 96.2 +/- 51.5 muA/cm(2) and a net Na(+) blood side to seawater side flux of 65.3 +/- 28.6 muA/cm(2).


Physiological properties of dissociated muscle fibres obtained from innervated and denervated adult rat muscle.

1. Adult rat flexor digitorum brevis muscles were dissociated by treatment with collagenase and trituration. Several hundred isolated fibres were obtained from each muscle. 2. Most isolated fibres appeared to be intact as judged by some morphological and physiological criteria, although resting membrane potentials were about -60 mV, which is somewhat lower than normal. 3. A small percentage of the muscle fibres were branched. 4. Acetylcholine sensitivity was measured iontophoretically. The sensitivity fell abruptly outside the margin of the end-plate. Extrajunctional sensitivty was detected on all fibres, and declined smoothly away from the end-plate to an undetectable level over a distance of about 200 micron. On a few fibres, ACh sensitivity was mapped circumferentially from the end-plate. It appeared to decline with distance in a manner similar to the longitudinal sensitivity gradient. 5. Fibres dissociated from muscles denervated a week earlier were sensitive to ACh everywhere on their surfaces.


The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery.

1. The membrane potential of the smooth muscle cells of the rabbit main pulmonary artery amounts to -57 mV, the length constant of the tissue is 1.48 mm and the time constant of the membrane 182 msec. On the basis of the electrical properties of its membrane, this smooth muscle tissue is classified as a single-unit type. During outward current pulses, the membrane shows marked rectification and action potentials can never be generated.2. Tetraethylammonium (10 mM) and procaine (5 mM) depolarize the membrane and increase the membrane resistance. By studying the effect of both substances on the (42)K efflux, it could be concluded that they reduce the K-permeability of the membrane. They also suppress the rectification of the membrane and increase the length constant of the membrane. In the presence of TEA and procaine, a graded response of the membrane can be induced by outward current pulses, but overshoot potentials never occur.3. Noradrenaline, in concentrations between 2 x 10(-8) and 10(-7)M, evokes contraction without depolarizing the membrane. When the concentration is increased above 2 x 10(-7)M, noradrenaline depolarizes the membrane and reduces the membrane resistance. A study of the effect of noradrenaline on the K, Cl and Na fluxes has revealed that it increases the permeability of the membrane for these three ions.4. The tissue concentrations of Na and K are 80 and 38 m-mole/kg wet wt., respectively. The amount of Cl in the cellular compartment was measured by an extrapolation procedure and found to be 13 m-mole/kg wet wt. The extracellular space measured with [(14)C]sorbitol is 550 ml./kg wet wt. and the dry wt./wet wt. ratio 19%. The calculated equilibrium potentials for K, Na and Cl (E(K), E(Na) and E(Cl)) are -83, +59 and -26 mV, respectively. In efflux experiments under steady-state conditions, the following rate constants have been calculated: 0.092 min(-1) for Na, 0.029 min(-1) for Cl and 0.0054 min(-1) for K. The calculated value for the ratio P(Na)/P(K) was 0.22 and for P(Cl)/P(K) 0.63.5. K-free solution and 2 x 10(-6)M ouabain depolarize the cells by about 8 mV. After exposure of the cells to K-free solution, they hyperpolarize on readmission of K, suggesting that part of the membrane potential could be due to electrogenic transport of ions.6. A decrease of external Ca depolarizes the cells and increases the membrane resistance. Na-deficiency hyperpolarizes these smooth muscle cells but this procedure does not prevent the depolarization induced by Ca deficiency.


Excitation-contraction coupling in the smooth muscle cells of the rabbit main pulmonary artery.

1. Increasing the external K concentration depolarizes the smooth muscle cells of the main pulmonary artery, and this depolarization reaches a maximal slope of 58 mV for a tenfold change of [K](o). The threshold depolarization for inducing contraction is at 4 mV and the maximal contraction is reached at a [K](o) of 58 mM.2. Noradrenaline concentrations between 2 x 10(-8)M and 10(-7)M induce tension without depolarizing the cells, but at higher concentrations noradrenaline not only elicits a large tension response but also depolarizes the cells in a dose-dependent way.3. The effect of noradrenaline on the pulmonary artery is appreciably modified by substituting sucrose for NaCl: the cells are slightly hyperpolarized and the tension response is very much reduced.4. By studying the tension response to noradrenaline in other experimental conditions which cause a small hyperpolarization of the cells, such as 5 mM-[Ca](o), 2.9 mM-[K](o) or a small depolarization, such as 11.9 mM-[K](o), it was found that a slight modification of the membrane potential can exert an important effect on the noradrenaline response.5. A simultaneous decrease of [Ca](o) and [Na](o) reduces the tension response to all noradrenaline concentrations. It was found that a reduction of [Na](o) exerts a more depressing effect than a reduction of [Ca](o). In interpreting these results we have to take into account changes of the membrane potential, of availability of Ca, and some competition between external Ca and Na.6. A study of the effect of different concentrations of noradrenaline in Krebs solutions and Ca-free solution has shown that concentrations up to 2.5 x 10(-7)M elicit contraction by increasing the Ca influx, while higher concentrations also induce a release of cellular Ca.7. Caffeine depolarizes the cells and reduces the membrane resistance. It modifies the K, Cl and Ca fluxes in the same way as noradrenaline, but it suppresses the mechanical response induced by noradrenaline.


Action of oleic acid on the exocrine pancreatic secretion of the conscious rat: evidence for an anti-cholecystokinin-pancreozymin factor.

The effects on exocrine pancreatic secretion of an intraduodenal infusion of oleic acid (2 ml in 60 min) has been assessed in conscious rats provided with a new type of duodenal cannula permitting the normal flow of pancreatic juice, but not of bile, between experiments.1. Intraduodenal oleic acid infusion induces an increased secretion of water and bicarbonate which is still significantly above basal values 90 min after the end of infusion. Protein output increased during the infusion, but protein concentration and output significantly decreased under basal levels 120 min and 150 min after infusion (respectively -63 and -57% of basal values at 150 min).2. No inhibition was found when oleic acid was introduced into the caecum or into the first 20 cm of ileum isolated from the rest of small intestine. On the contrary, inhibition of protein secretion was induced immediately by intra-ileal oleic acid infusion.3. Inhibition of protein secretion secondary to intra-ileal oleic acid infusion was transmitted from a donor rat to a receiver rat by means of a cross-circulation.4. It is concluded that oleic acid induces an immediate and long lasting increase in water and bicarbonate secretion. During the infusion of oleic acid, protein output is increased, followed by an inhibition. This delayed inhibition stems from the second part of the small intestine and was transferred from one rat to another by cross-circulation: it is speculated that oleic acid releases in the conscious rat (from the distal part of the small intestine) a hormonal factor inhibiting pancreatic secretion.


[Experimental studies concerning the hemodynamic and metabolic functions in the canine heart-lung preparation supported by a donor (author's transl)].

In the usual canine heart-lung preparation the coronary blood flow does not remain constant, but increases steadily ; usually, at the moment of the set up of the preparation the coronary blood flow was about 20 ml/min/100 g heart. However, in the course of 2 approximately 3 hours it becomes more than 150 ml/min/100 g heart and the responsiveness of the coronary artery is completely lost under this condition. Concurrently with the increase in the coronary flow, cardiac functions tend to deteriorate. In order to eliminate those experimental disadvantages, we added a donor dog to the heart-lung preparation. It was found that the support by the donor dog resulted in the complete improvement of the above-mentioned deterioration ; the coronary circulation (coronary blood flow and coronary artery and sinus blood oxygen saturation), cardiac function (cardiac output, right atrial pressure, heart rate and others) and cardiac metabolism (myocardial oxygen consumption, mycardial redox potential and others) were kept constant at a favorable state for more than 10 hours.


Developmental changes in the inward current of the action potential of Rohon-Beard neurones.

1. Rohon-Beard cells in the spinal cord of Xenopus tadpoles have been studied in animals from early neural tube to free-swimming larval stages. The onset and further development of electrical excitability of these neurones has been investigated in different ionic environments, to determine the ionic species carrying the inward current of the action potential.2. The cells appear inexcitable at early stages (Nieuwkoop & Faber stages 18-20) and do not give action potentials to depolarizing current pulses.3. The action potential is first recorded at stage 20. (A) The inward current is carried by Ca(2+) at stages 20-25, since it is blocked by mm quantitites of La(3+), Co(2+) or Mn(2+) and is unaffected by removal of Na(+) or the addition of tetrodotoxin (TTX). (B) The action potential is an elevated plateau of long duration (mean 190 msec at stages 20-22). The duration decreases exponentially with repetitive stimulation. (C) The specific Ca(2+) conductance (g(Ca)) at the onset of the plateau of the action potential is 2.6 x 10(-4) mho/cm(2). Calculations show that a single action potential raises [Ca(2+)](1) by more than 100-fold.4. At later times (stages 25-40), the inward current of the action potential is carried by both Na(+) and Ca(2+): the action potential has two components, an initial spike which is blocked by removal of Na(+) or addition of TTX, followed by a plateau which is blocked by La(3+), Co(2+) or Mn(2+).5. Finally (stages 40-51), the inward current is primarily carried by Na(+), since the action potential is blocked only by removal of Na(+) or addition of TTX, and the overshoot agrees with the prediction of the Nernst equation for a Na-selective membrane. When the outward current channel is blocked and cells exposed to Na-free solutions, 67% of cells at the latest stages studied were incapable of producing action potentials in which the inward current is carried by divalent cations.6. The duration of the action potential decreases from a maximum of about 1000 msec to about 1 msec during development. The maximum input resistance (R(in)) decreases from ca. 1000 to 100 MOmega.7. The calcium action potential may play a role in the development of excitability and the growth of the neurones.


Additional notes on the coccidian parasites of the soft-shell turtle, Trionyx spiniferus Le Sueur, in Iowa, with a description of Eimeria vesicostieda sp. n.

Oocysts of Eimeria dericksoni Roudabush, Eimeria mascoutini Wacha & Christiansen, and Eimeria vesicostieda sp. n. were isolated from the Spiny Soft-shell Turtle, Trionyx spiniferus LeSueur, in Iowa. The sporulated oocysts of E. dericksoni are redescribed to include, for the first time, the dimensions of the sporocysts (6.0-8.5 x 3.0 5.0 micrometer) ant the structural appearance of the Stieda body (thinly convex); the oocysts of E. vesicostieda are newly described as being thick-walled, narrowly avoid to narrowly ellipsoid, measuring 22.0-25.5 x 16.5-20.5 micrometer, and having a polar granule, a sporocyst residuum, and a vesicle-like Stieda body; the oocysts of E. mascoutini are documented photographically.


Eimeria crotalviridis sp. n. from prairie rattlesnakes, Crotalus viridis viridis, in New Mexico with data on excystation of sporozoites and ultrastructure of the oocyst wall.

Oocysts of Eimeria crotalviridis sp. n. are described from praire rattlesnakes, Crotalus viridis viridis in New Mexico on the basis of light and electron microscopy and in vitro excystation of sporozoites. Sporulated oocysts of E. crotalviridis are elliptical, 26.4 X 22.3 (23-29 X 20-24) micrometer with ovoid sporocysts 11.7 X 8.1 (11-13 X 7-9) micromiter. A micropyle, micropyle cap and polar bodies are absent, but oocyst and sporocyst residua and Stieda and substieda bodies are present. Excysted sporozoites are 12.4 X 2.8 (11-13 X 2-3) micromiter and have 1 large posterior refractile body and a nucleus with a prominent nucleolus. Ultrastructurally, the oocyst wall has 2 layers, a thick, electron-dense, highly sculptured outer layer composed of a fine granular matrix and a thin, granular, osmiophilic inner layer, separated from the outer layer by at least one unit membrane. These layers are 441 (353-510) and 21.6 (19-29) nm thick, respectively. Within 15 min after exposure to a trypsin-sodium taurocholate fluid, sporozoites of E. crotalviridis excysted from 5-month-old sporocysts.


Eimeria zapi sp. n. from the meadow jumping mouse, Zapus hudsonius Zimmerman in southwestern Michigan.

Four of 5 meadow jumping mice (Zapus hudsonius) captured had in their feces a previously undescribed species of Eimeria which is named Eimeria zapi sp. n. The sporulated oocysts measured 21.7 (19.5-24.0) x 20.3 (17.5-23.0) micrometer. The single-layered oocyst wall was 1.5 micrometer thick, rough, pitted and appeared clear-to-amber. Usually 2 polar granules could be seen. An oocyst residuum was not observed. Each sporocyst averaged 16.0 (12.5-18.0) x 9.7 (7.5-11.5)micrometer. A substiedal body was present. The sporocyst residuum consisted of a membrane-enclosed packet of 15 to 20 granules. This is the first species of Eimeria to be described from the genus Zapus.


Ciliary membranes and mating substances in Paramecium caudatum.

Cilia detached from mating reactive cells of Paramecium caudatum were fractionated for the purpose of identifying the structural component bearing mating substances. Purified axoneme fractions had no mating reactivity. The membrane fraction obtained by dialyzing against a solution of Tris-EDTA (0.1 mm EDTA, 1 mM Tris-HCI, pH 7.6) and 0.6 m KCI, and then by centrifuging over 40% (w/v) sucrose was strongly reactive. No mating reactivity was detected in the soluble fractions containing axonemal and matrix proteins. The results indicate that the mating substances in active form are localized only on the ciliary membranes.


Cultivation of Leishmania donovani and Leishmania braziliensis in defined media: nutritional requirements.

Nutritional requirements of promastigotes of Leishmania donovani and Leishmania braziliensis were studied in modifications of a simple defined culture medium. "Continuous growth," considered as propagation through 10 successive passages, was supported by inorganic salts, 14 l-amino acids (arginine, cysteine, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine, valine), glucose, adenosine, and a mixture of 11 vitamins and related growth factors. Purified defatted bovine serum albumin proved beneficial. The nutritional needs of the above species of Leishmania differ from those of 2 other hemoflagellate species, Leishmania tarentolae and Crithidia fasciculata, for which glucose, proline and glutamine were found to be nonessential. It is suggested that lower hemoflagellates may be capable of synthesizing these substrates de novo. Leishmania donovani and L. braziliensis required higher levels of folic acid than L. tarentolae, probably due to the fact that folates are involved as cofactors in the biosyntheses of pyrimidines and serine. Although the mixtures reported here cannot be regarded as "minimal essential" media, they are considerably less complex than the ones employed so far for cultivating hemoflagellates, and are therefore well suited for studies related to nutrition and biosynthetic capabilities of Trypanosomatids.


Effect of berenil on growth, mitochondrial DNA and respiration of Leishmania tarentolae promastigotes.

Incubation of Leishmania tarentolae promastigotes in 1.0 microgram/ml Berenil for 96 hr resulted in approximately 33% inhibition of cell growth and approximately 42.5% dyskinetoplasty in the cell population. The buoyant density of kinetoplast DNA (kDNA), p = 1.703 g/ml, remained unchanged after 96-hr exposure to the drug. Endogenous respiration as well as proline- and glucose-induced respiration dropped markedly after 36-hr exposure to Berenil. This drop occurred approximately 12 hr before the onset of dyskinetoplasty, a result which suggests that this drug adversely affects mitochondrial respiratory activity of the promastigotes.


Inter-strain variability of structural proteins in Tetrahymena.

The high molecular weight proteins found in isolated pellicles of Tetrahymena have been compared in several individual strains within the genus using SDS polyacrylamide gel electrophoresis. Three variants of the beta-protein of epiplasm (MW 174,000; 155,000; 145,00) and 2 of the C-protein (MW 140,000; 122,000) were found among the strains examined. No variation was observed in the major kinetodesmal fiber protein (MW 250,000). The variation found between strains in the proteins of a structure which is (as far as we know) the same in all strains indicates a disjunction between evolutionary change at the 2 levels of organization. The taxonomic implications of the observed variation in structural proteins in Tetrahymena are discussed.


Identification of Leishmania spp. by radiorespirometry.

Preliminary investigation of the application of radiorespirometric technic to protozoan parasites of man indicates a potential for rapid identification. This technic, developed for identification of bacteria, was modified for use with culture forms of Leishmania. Five strains of Leishmania were compared: 2 of L. donovani, 2S and K; L. brasilensis, 2936 and B; and 1 of L. tropica, A. Consisent and rapid (approximately 2 hr) identification was obtained by the radiorespirometric procedure. A computer-type analysis of the radiorespirometric profiles of the 5 strains permitted correct identification of each isolate at the strain level 100% of the time. This technic offers several advantages over many current procedures for identification of protozoan parasites: (A) It is simple, rapid and highly reproducible, (B) Since it does not rely on visual or spectrophotometric determination, it may be conducted in the presence of optically complex substances. (C) It requires relatively low numbers of organisms (approximately 2 x 10(5)/14C-labeled substrate). (D) It is based on differential enzymic activity between species and strains of organisms and therefore, ultimately, on inherent genetic determinates of the parasites. (E) Further development of the procedure and accumulation of a data reference "bank" would allow automation of most of the identification process.


Effects of the optical isomers of alpha-chlorohydrin on glycolysis by ram testicular spermatozoa and the fertility of male rats.

When 0-1 mM-S alpha-chlorohydrin was present in incubations, glycolysis by ram testicular spermatozoa was almost completely inhibited whereas 10 mM-R alpha-chlorohydrin had no effect. Male rats dosed orally with S alpha-chlorohydrin (3-25 mg/kg/day) became much less fertile than controls but those dosed with R alpha-chlorohydrin (13 mg/kg/day) did not. The loss of fertility was associated with a reduced ability of spermatozoa from the cauda epididymidis of these rats to oxidize glucose. It is concluded that the S enantiomer is responsible for both the inhibition of sperm glycolysis and the reduction in fertility caused by the racemic mixture of alpha-chlorohydrin.


Membrane potential of guinea-pig spermatozoa.

The membrane potential of guinea-pig spermatozoa was investigated by using the fluorescent dye, diS-C3-(5). The potential did not vary when K replaced Na in the suspending medium, and in a physiological salt solution the resting potential was found to be about +13 mV.


Ovarian atrophy resulting from urethane injection of neonatal mice.

Treatment of neonatal mice with urethane (0-5 or 0-75 mg/g body wt, i.p.) caused a lack of follicular development beyond the primordial stage. An effect of the thymus on ovarian development is inferred.


Fertility of dairy cattle after artificial insemination with semen frozen in a lipoprotein diluent.

A lipoprotein separated from egg yolk by centrifugation and column chromatography was used to prepare a diluent containing 2-9% trisodium citrate. 2H2O (pH 7-0) and 7% glycerol. Ejaculates from Friesian bulls were split between this and two control diluents containing egg yolk, glycerol and citrate or lactose and used to inseminate once 1782 unselected Friesian cows. By 16 weeks after insemination with semen frozen in the egg yolk-lactose, egg yolk-citrate or lipoprotein-citrate diluents, 66-4, 67-1 and 66-1% of cows, respectively, had not returned to service.


Relationship between testicular blood flow, testosterone secretion and spermatogenic activity in young and adult wild red foxes (Vulpes vulpes).

Testicular capillary blood flow (TCBF) was measured by the radioactive inert gas clearance technique throughout the reproductive life of young adult foxes and was related to the spermatogenic and androgenic activities of the testis. Mean (+/-S.E.M.) blood flow (ml min-1 g-1) was maximal in January in adults during the mating period (0-65 +/- 0-03), and in pubertal animals (0-62 +/- 0-04). At this time spermatozoa were observed in the testes of all animals, but testicular weight and circulating testosterone levels were lower in the pubescent foxes than in the adults. TCBF was minimal during immaturity (0-29 +/- 0-03) and during the resting period of the adult (0-12 +/- 0-01). These values were associated with a low testosterone level and with the multiplication of gonocytes in the young or with the seasonal very low spermatogenic activity in the adult. During the prepubertal period, TCBF slowly increased and was accompanied by testicular growth. In the adult, in September, TCBF rapidly increased without changes of testicular size and then slowly increased as the testes enlarged. High plasma testosterone concentrations occurred later. During the period of testicular regression, TCBF, testicular size, spermatogenic and androgenic activities decreased together.


Changes in the composition of maternal plasma, fetal plasma and fetal extraembryonic fluid during gestation in the rat.

The changes in the biochemical composition of maternal plasma, fetal plasma and fetal extraembryonic fluid were studied in Wistar rats from Days 13 1/2 to 21 1/2 of gestation. During this period, there was an increase in maternal plasma volume and total blood volume. The total protein concentration decreased, but little change was observed in the protein pattern, total alpha-amino nitrogen, urea nitrogen and sodium concentration. In fetal plasma, total protein concentration increased progressively with a prominent increase in albumin near term. The albumin:globulin ratio was lower than that in maternal plasma because of the presence of two alpha-fetoproteins and four transferrins. The concentration of alpha-amino nitrogen was higher than that in maternal plasma but the urea nitrogen level did not change significantly. The fetal extraembryonic fluid reflected the changes in composition of fetal plasma, especially in the protein pattern, and concentrations of alpha-amino nitrogen and sodium. Total protein and urea nitrogen increased markedly in concentration near term but there was reduction in the fluid volume at this time.


Reproductive potential in female cattle discarded as infertile.

Dairy cattle were served at consecutive heats up to three times each; they were then slaughtered, and the genital tracts were examined. Seventy-four cattle had been discarded from herds because they had not bred; 14 had never calved, and 14 were primiparous. Of these 28 animals, 12 (43%) conceived readily, and had normal pregnancies; normal genital tracts were found at slaughter. Eleven of the 16 animals that did not conceive had normal genitalia. The remaining 46  animals were mature cows, with a mean parity of 4-9; 9 (19-6%) became pregnant and had live embryos at autopsy, while in 7 other cows (15-2%) conception had been followed by embryonic death. Five of the uteri associated with these 16 conceptions showed pathological changes. Thirty of the 46 mature cows (65%) did not conceive; 12 (40%) had normal genitalia, and 18 (60%) showed severe pathological changes in the uterus and/or oviduct. Nine 'control' cows discarded because of poor milk yield were infertile, but 5 cows, discarded for various other reasons, all bred normally.


Evidence for the facilitated diffusion of glucose into rabbit oviductal fluid.

Glucose movement into the oviductal fluid of rabbits was studied in anaesthetized animals. The oviducts were cannulated at each end, and 2 ml 0-9% NaCl at 37 degrees C were recirculated through the lumen for 4 h. D-Glucose appeared linearly in the fluid, reaching an average concentration of 2-6 mM. The rate of D-glucose appearance was 17 times greater than that of L-glucose, infused intravenously, suggesting that a component of the D-glucose movement operated by facilitated diffusion. The oviduct was unable to move glucose against an adverse plasma to lumen concentration gradient. We suggest that the glucose entering the oviductal fluid originates in the plasma and that the mucosal portion of the oviduct is responsible for this sugar transfer.


Pregnancy in patients with hemoglobinopathies and thalassemias.

The availability of sophisticated laboratory procedures has made the diagnosis of many hemoglobinopathies and thalassemias simple. Structural alteration of the polypeptide chains and defects in the rate of synthesis of any of the polypeptide chains are the most common abnormalities: hemoglobins S, C and D are examples of the former, and the thalassemias are examples of the latter. The pathophysiology, clinical manifestations and individual variation of each abnormality are significantly different. Early diagnosis and the knowledge of the pathophysiology together with careful and frequent follow-up are necessary for providing better medical care. Pregnancy in a patient with a diagnosis of hemoglobinopathy or thalassemia certainly speaks for risks to both the mother and fetus. Management of each case has to be planned individually to provide optimal medical and supportive care. We have found a special combined hematology-obstetrics clinic to be helpful in the follow-up of these high-risk patients.


Disseminated intravascular coagulation in pregnancy.

The DIC syndrome is the most common cause of an abnormal hemorrhage tendency during pregnancy and the puerperium and reflects systemic activation of the coagulation cascade by circulating thromboplastic material, with secondary activation of the fibrinolytic system. Its presence in a pregnant patient almost invariably is evidence of an underlying obstetric disorder such as abruptio placentae, eclampsia, retention of a dead fetus, amniotic fluid embolism, placental retention or bacterial sepsis. Diagnosis of the DIC syndrome rests on the demonstration of reduced levels of fibrinogen and platelets, prolongation of the thrombin, prothrombin and partial thromboplastin times, and the presence of fibrin/fibrinogen degradation products (FDP) in the serum. Therapy consists of prompt removal of the source of procoagulant material, replacement of depleted clotting factors and, in some cases, anti-coagulation with heparin.