Pharmacokinetics of technetium-99m diphosphonate.

Increased diagnostic information may be derived with Tc-99m diphosphonate from a detailed kinetic analysis of blood disappearance, urinary excretion, and quantitative assessment of skeletal uptake. Blood and urine determinations were studied in three populations: normal volunteers, patients with negative bone scans, and patients with positive bone scans. Quantitative imaging studies were performed in normal volunteers and patients with a scintillation camera interfaced to a computer. All subjects were scanned in the lower lumbar region up to 1 hr after Tc-99m diphosphonate administration. Blood levels exhibited a triexponential clearance pattern. Significant (p less than 0.05) differences were observed for the 5-min blood and 0-1 hr urine values among the various groups. The computer-generated images showed an initial early uptake in bone, kidneys and soft tissue. Thereafter, a parallel fall-off in activity was observed in kidney and soft tissue, with a concomitant increase in bone. Skeletal uptake was different for normal and diseased bone.


Effect of oxygen on the reduction of pertechnetate by stannous ion.

The effect of oxygen on the reduction of sodium pertechnetate by stannous chloride has been investigated using a paper electrophoresis method. It has been shown that oxygen interferes with the reduction process by oxidizing stannous ion, Sn(II), to stannic, Sn(IV), thereby leaving less Sn(II) available for the reduction of pertechnetate ion. In a solution of 1.66 X 13(-3)M TcO4- saturated with oxygen, a 3.4 molar ratio of Sn(II) to TcO4- was required for complete reduction of TcO4-, whereas in a nitrogen atmosphere, a 2.4 molar ratio was required for the same purpose. The oxygen interference increases as the concentration of TcO4- decreases. In a nitrogen atmosphere, 1.40 and 10.05 molar ratios of Sn(II) to TcO4- were required for the complete reduction of 1.66 X 10(-2)M and 1.66 X 10(-5)M TcO4- respectively. Once the reduction is accomplished, however, it is not easily reversible. Bubbling with oxygen for 1 hr had no effect on the quantity of reduced technetium.


An evaluation of radiocolloid sizing techniques.

Techniques for sizing radiocolloids are reviewed. The small size range (1-100 nm) of many radiocolloids and their polydispersity limit the choice of the technique used. To compare several techniques directly, the particle size of Technetium-99m sulfide colloid was studied using Nuclepore filtration, ultracentrifugation and electron microscopy. The last of these was adopted as the method of choice. Using this technique, the particle size and shape of colloids below 100 nm can be accurately determined. Technetium-99m antimony sulfide colloid and indium-113m hydroxide were then examined by electron microscopy, and the chemical nature of the particles was determined by x-ray fluorescence analysis. Results resolved the size discrepancies reported in the literature and demonstrated the importance of identifying the chemical nature of the particles under examination.


Bismuth germanate as a potential scintillation detector in positron cameras.

Timing and energy resolutions of the bismuth germanate (Bi4Ge3O12) scintillation crystals were studied, with particular respect to a positron-camera application. In comparison with the NaI(Tl) system, the detection efficiency for annihilation radiation is more than triple, and coincidence detection efficiency is more than ten times as good. This paper explores the properties of the new scintillator material and their bearing on the spatial resolution and the efficiency of coincidence detection in positron cameras with stationary ring detectors.


Determination of radionuclide concentrations with positron CT scanning (PETT): concise communication.

A series of experiments was undertaken to evaluate the response of a positron emission transverse tomograph (PETT) to measured radionuclide concentrations similar to those encountered in human studies. The correlation between the response of the imaging system (mean PETT number/min), and the concentration of the radioactivity producing the output data, was linear with a computed sensitivity of 2720 PETT number/min, per micronCi/ml, per picture element, for a radionuclide (100% beta+) contained in either of two phantoms and imaged with a reduction of 1.5 cm. It was concluded that the output data are essentially independent of the imaged object's physical dimensions for the range of 18-28-cm diam and faithfully reflect the regional radioactivity concentration within the object, provided valid attenuation correction is achieved and the sampled area is not compromised by the imaging system's limitations of spatial resolution.


Radionuclide left ventriculography with the slant hole collimator.

A 30 degrees slant-hole collimator was used during radionuclide ventriculography of the cardiac blood pool to improve imaging of the heart in both the modified left anterior oblique (MLAO) and right anterior oblique (RAO) views. In the MLAO view, with the holes slanted caudally, good separation between the left atrium and left ventricle was achieved, and the septum was displayed without foreshortening. In the RAO view with the collimator flat against the chest there was better resolution of the cardiac apex. The results of ejection fraction and wall motion analysis in these patients correlated well with contrast ventriculography (r=0.94). Combination of the slant-hole collimator, in vivo red blood cell labeling with stannous pyrophosphate, simultaneous collection of all phases of the cardiac cycle, and cine mode display, provide a practical system for the noninvasive measurement of left ventricular performance parameters.


Effect of deep inspiration on airway conductance in subjects with allergic rhinitis and allergic asthma.

We measured specific airway conductance (Gaw/Vtg) in a body plethysmograph before and after a deep inspiratory maneuver in 8 subjects with allergic rhinitis and 8 subjects with allergic asthma. In hay fever subjects deep inspiration had no effect on Gaw/Vtg if it was performed in the control state; however, when methacholine-induced bronchoconstriction was present, deep inspiration transiently increased Gaw/Vtg. In asthmatic subjects deep inspiration was followed by a transeint fall in baseline Gaw/Vtg in the control state; however, when bronchoconstriction was present, deep inspiration was followed by small and variable changes in Gaw/Vtg in 7 subjects and marked improvement in Gaw/Vtg in 1 subject. In asthmatic subjects the bronchoconstrictor response to deep inspiration performed in the control state is thought to be due to reflex changes in bronchomotor tone mediated by cholinergic (vagal) nerve pathways. Like asthmatic subjects, hay fever subjects, hay fever subjects also possess cholinergic-mediated airway hyperreactivity compared with normals. Our results indicate that, in spite of their increased airway reactivity, hay fever subjects respond more like normal subjects than like asthmatic subjects after a deep inspiratory maneuver.


Allergic skin testing: a clinical investigation.

Forty patients were administered a total of 2,395 skin tests in order to assess the effects of method, concentration, diluent, manufacturer, and mixtures on patient reaction to inhalant extract solutions. The prick method was found to be superior to the scratch method. The intracutaneous technique exhibited the greatest degree of specificity. Patients reacted at a higher level to higher concentrations of extract solution, descending to a lower level of reaction to lesser concentrations of extract solution. Patient reactions were variable to aqueous vs glycerin solutions. Clear differences in the potency of extract solutions produced by manufacturers A, B, and C were evident. Specifically, the products of manufacturer C were least potent. The results illustrate the possibility of a dilution factor existing in mixtures of extract solutions, producing a decrease in their potency when compared to the potency of their individually administered components. A technique with the potential for wide acceptance and clinical applicability is proposed.


Inhibition of homocytotropic antibody responses in adult inbred mice by previous feeding of the specific antigen.

Profound and prolonged states of specific immunologic tolerance were induced in adult mice of high-responder genetic background by a single exposure to moderate doses of the specific antigen by digestive route.


Methacholine and physostigmine airway reactivity in asthmatic and nonasthmatic subjects.

Inhalation challenges using methacholine and physostigmine were performed in 3 human asthmatic and 3 nonallergic normal subjects. Plethysmographic measurements of specific airways conductance (Gaw/Vtg) were used to monitor the response. The dose required to produce a 17% fall in Gaw/Vtg was significantly lower in asthmatic subjects than in normal subjects for both physostigmine (p less than 0.0125) and methacholine (p less than 0.05). Moreover, in all subjects the relative airway sensitivity to methacholine correlated with the relative airway sensitivity to physostigmine. Both methacholine and physostigmine are cholinergic agents. Whereas methacholine acts directly at the end organ cholinergic receptor, physostigmine acts by increasing release and decreasing destruction of endogenous acetycholine at the vagal distal innervation. This suggests that the cholinergic airway hyperreactivity characteristic of asthma is a manifestation of end organ hypersensitivity.


Abnormalities of leukotaxis in atopic dermatitis.

Leukocyte chemotaxis studies were performed in 14 patients with atopic dermatitis. Monocyte chemotactic responsiveness (MCR), polymorphonuclear leukocyte (PMN) chemotactic responsiveness (PCR), and patient serum inhibition of normal monocyte chemotaxis were evaluated. The most common defect noted was depressed MCR. This was found in 8 of the 14 patients and was associated with a chemotactic inhibitor in the serum of 5 of 6 of the 8 with depressed MCR whose sera were so tested. Depressed PCR was found in 3 of 10 patients studied. Ten of the 14 patients had depressed chemotaxis of at least one cell type. Depressed chemotaxis was not related to the presence of infection, to the serum IgE level, or to the severity of the eczema, and it could not be produced in vitro by incubating normal cells with histamine or IgE myeloma. These studies demonstrate a high frequency of leukocyte chemotactic abnormalities in patients with severe atopic dermatitis. Elucidation of the clinical significance of the leukotactic abnormalities observed and determination of whether they are basic or secondary to the disease process must await further study.


Aging and insulin resistance in a group of nonobese male volunteers.

The relationship of age to insulin resistance was determined in 100 nonobese men whose ages ranged from 22 to 69 years. Seventy of the 100 subjects had normal glucose tolerance, and 30 had chemical diabetes. Insulin resistance was estimated by measuring the steady-state plasma glucose response to a continuous infusion of insulin, glucose, epinephrine, and propranolol. This approach permitted inhibition of endogenous insulin release, achievement of a comparable steady-state plasma level of exogenous insulin, and use of the height of the steady-state plasma glucose response as a direct estimate of insulin resistance. With this experimental method, no correlation was found between age and insulin resistance over the age span of the experimental population. Furthermore, there was no correlation between age and the height of the plasma glucose response to an oral glucose challenge in this population of nonobese, healthy ambulatory men.


Signs of sensory deprivation versus cerebral injury in post-hip-fracture patients.

Patients with a primary diagnosis of "postoperative hip fracture" often have a poor prognosis because of their inability to participate in rehabilitation programs. They tend to remain in a state of physical inactivity and sensory deprivation. The signs and symptoms of head injury associated with the hip fracture may be overlooked and attributed to sensory deprivation. Thirty-nine patients with fractured hip and 18 with multiple fractures were studied by means of electroencephalography, echoencephalography, and computer axial tomography. In 7, the findings indicated a cerebral lesion. At operation, a subdural hematoma was found in 5 patients and a tumor in 2; all but one made a dramatic recovery. Thus, after hip fracture, it is important that the patient be tested appropriately so that signs and symptoms of sensory deprivation may not be confused with those of an occult head injury. When indicated, surgical intervention may be a life-saving process.


Incidence of mental illness in the aged: unmasking the effects of a diagnosis of chronic brain syndrome.

A combination of three psychiatric screening tests was used to uncover the extent of affective-psychotic symptoms, the indications of "chronic brain syndrome," and the perceptual limitations among two selected populations of elderly persons. It was found that 25% of 48 residents in a home for the aged, and 9% of 45 members in a social club, had four or more affective-psychotic complaints. In the former group, 75% had symptoms of moderate to severe "chronic brain syndrome," versus 7% in the latter group. Among the residents of the home, 10% had serious disturbances as measured by all three tests. The significant number of affective-psychotic symptoms found in this population with extensive manifestations classifiable as "chronic brain syndrome" indicates that this diagnosis should not be allowed to preclude regular psychiatric evaluation of these elderly patients. When a specific diagnosis is established, available treatment modalities should be provided as needed.


True aneurysm of the radial artery: report of a case with long-term follow-up.

Reports on aneurysm of the arteries of the wrist and hand are relatively rare. Presented here is a case of true aneurysm of the radial artery in a 41-year-old-man. The patient had an enlarging painful swelling on the volar aspect of the left wrist, of six months' duration. Under local anesthesia, a transverse incision over the wrist crease revealed an arterial aneurysm. The aneurysm was excised, followed by end-to-end anastomosis. The patient recovered uneventfully and was discharged nine days after the operation. A follow-up arteriogram, five days later, showed a patent radial artery with good blood flow. This is an excellent example of a successful reconstructive surgical procedure involving a small artery.


The second heart sound in old age.

The second heart sound was studied by phonocardiography and carotid tracings in 103 elderly subjects without overt evidence of heart disease. Their ages ranged from 60 to 99 years. A normal type of splitting was found in 55.3%, and a single sound in 41.7%. The difference between these percentages and those found in 60 normal younger persons was not significant. Thus, a single second sound should not be considered a typical finding in old age. However, a reverse type of splitting, noted in only 3 patients, should be regarded as evidence of severe latent heart disease.


Binocular vision therapy for general practice.

Guidelines are given for selection of patients who need binocular visual therapy. These guidelines are useful for the optometrist who wishes to start binocular vision training in his practice. Treatment techniques for each type of binocular problem are discussed. Case reports are included which detail diagnosis and treatment.


The future of vision screening.

The future of vision screening is presently receiving heated debate. Recent federal legislative activity in the area of comprehensive health planning has caused renewed interest in vision screening. Optometric recommendations supported at various governmental levels call for the development of standards for comprehensive vision screening of school children on a national scale. This paper attempts to review the philosophy and justification for school vision screening and to bring the readers up to date on related governmental activity. The question of adequate manpower to implement a nationwide vision screening program is discussed, and an argument is developed for preparing school nurse practitioners to assume an expanded role in comprehensive vision screening.


An optical evaluation of book retinoscopy.

The technique known as book retinoscopy has been used for more than 25 years to evaluate visual performance. The lack of a clear explanation of the phenomena observed during book retinoscopy has led to some confusion regarding the interpretation of the phenomena. This paper shows that all of the changes that are observed can be explained by the optical effects of accommodative changes and eye movements.


Refractive amblyopia: its classification, etiology, and epidemiology.

The traditional classification of functional amblyopia and von Noorden's classification are compared to a problem-oriented classification. The newly proposed classification is different from the others primarily by its inclusion of refractive amblyopia. The etiology and epidemiology of refractive amblyopia are also discussed.


The cause of blindness in children: a review of the literature.

A review of the epidemiological literature dealing with the distribution of affections causing blindness in children was performed. Twenty-one studies throughout the world during the past twenty years were found and analyzed. The emergence of genetic factors and the decline of infectious factors as causative agents is discussed with the emphasis on the need for prevention from a public health standpoint.


A non-cycloplegic refraction technique for infants and young children.

An objective, near-retinoscopy technique for assessing non-cyloplegic refractions in infants and young children is presented. The technique involves performing retinoscopy at near in an otherwise dark room, as the patient fixates the retinoscope light with one eye, while the other is occluded. Data are presented which support the reliability and validity of this technique in adults and infants.


Radiobichemistry of phytodrugs: II. Activity of Altoside (r) and Altozar (R) in the biosynthesis of proteins and RNA in larvae of shrimps in vivo studied by leucine-U-14C and uridine-2-14C.

The present communication concerns the investigation of the effect of various concentrations of Altosid (R), J.H.A., on the biosynthesis of proteins and RNA in cultures of shrimp larvae in vivo measured by the uptake up Leucine, U-14C and Uridine-2-14C. The incorporation of Leucine follows different behaviour in the presence of either 0.01 or 1 ppm concentration of J.H.A.. At any dose Altosid (R) and Altozar (R) decrease the protein synthesis in the larvae of shrimps also at concentrations of 0.01 ppm, the main dose used for their application. In fact in these condition the synthesis of proteins is lower than in the control. For the RNA biosynthesis the uptake of Uridine is much higher in the presence of J.H.A. than in the control. It is suggested then an abnormal s-RNA is formed in the first hours, which does not synthetize proteins.


Metabolism of pentachlorophenol by a soil microbe.

Metabolism of pentachlorophenol (PCP)-ring-14C(U) by a microorganism (Pseudomonas sp.) isolated from soil was examined. The microorganism degraded PCP-14C rapidly, and released 14CO2 equivalent to approximately 50% of the PCP-14c added to the bacterial cell suspension in 1 hour of incubation. The results of amino acid analysis of the bacterial cells incubated with PCP-14C showed that radioactive carbon derived from PCP-14C was incorporated rapidly into the cell constituents, and that the pattern of 14C-amino acids in the cell constituents was not much different between the 15 minute and 24 hour incubation periods. Intermediate metabolities of PCP isolated from the incubation medium were identified as tetrachlorocatechol and tetrachlorohydroquinone by spectral analyses.


Relationship between omega values and parathion sorption capacity in soils.

The relationship between Lambert's omega (omega), an idex for active fraction of soil organic matter governing pesticide sorption, and parathion sorption capacity (y) in several Indian soils was studied using 14C-labeled parathion. A regression equation log y=1.984 - 0.279 1/omega accounted for 99.5% variation. The omega values were affected by soil to solution ratios.


4-(p-Nitrobenzyl)pyridine as a spray reagent for the thin-layer chromatographic detection of dimethyl tetrachloroterphthalate herbicide.

The developed thin-layer chromatogram of DCPA (Dacthal) is sprayed with 4-(p-nitrobenzyl)pyridine chromogenic reagent followed by ammonium carbonate solution. The chromatogram is then heated in an over at 130 degrees C for 20 minutes. When cool, the chromatogram is sprayed with tetraethylenepentamine reagent. DCPA spots appear blue against a white background. The sensitivity of this test is about 1 microgram. The procedure is useful to detect DCPA in water and in soil.


Some models for the adsorption kinetics of pesticides in soil.

Three models describing adsorption-desorption kinetics of pesticides in soil, that could be incorporated into computer programs on pesticide movement in soil, were discussed, The first model involved single first-order rate equations for adsorption and desorption. Results from an analytical and a numerical solution for local equilibration were compared. Concentration-time relationships for the solution and absorbed phases were calculated for different rate constants, initial conditions, and partition ratios at equilibrium. The second model described simultaneous adsorption-desorption equilibration with two mechanisms, both with their own rate constants. After a comparatively fast equilibration with the first mechanism, there was a gradual increase in extent of overall-adsorption, accompanied with a shift to greater amounts adsorbed by the second mechanism. With the thrid model, adsorption equilibration occurred by diffusion into a stagnant region. With diffusion distances ranging from 0.1 to 4.0 cm, the time needed for approach to adsorption equilibrium varied from about 0.25 days to about one year. Some of the possibilities of these models were discussed considering published experimental results.


The political economy on national health insurance. Policy analysis and political evaluation.

National health insurance (NHI) is discussed as a redistributive issue (that is, conflict over it is characterized by stable coalitions with important ideological differences). Discussion of policy alternatives has been intensified, but obscured, by a rhetoric which insists that the medical care system is in crisis. Both rhetoric and discussion point to three problem areas: cost, quality, and distribution of care. Three kinds of NHI proposals exist--minimal intervention measurees (e.g., AMAs Medicredit proposal), major government action (e.g., Kennedy-Corman), and mixed strategies (e.g., CHIP). While these have different potentials for mitigating the problem areas discussed, none can provide complete solutions. Rather, the goal of NHI is to avert financial catastrophe for families and individuals. The emergence of Democratic majorities in Congress and a Democratic White House increases the chances that some NHI plan will be adopted. Political analysis suggests that, short of aggressive leadership committed to a comprehensive scheme, a "middle ground" solution will be outcome.


The economics of moral values. Policy implications.

This paper attempts to determine the extent to which the growing acceptance of deviant behaviors (sexual, sumptuary, and regarding abortion and euthanasia) is related to economic considerations and to draw out some of the attendant implications for health policy in light of notions of social justice. The analysis suggests that economic factors are very influential if not determining variables in this relationship and that they may conflict with "higher-order values" such as human dignity and respect for human life as bases for policy formulation, particularly with respect to the care of the elderly.


The effect of physician-controlled health insurance. U.S. v. Oregon State Medical Society.

The trial record in an antitrust case against the Oregon State Medical Society, finally decided in 1952, was examined to reconstruct the behavior of a competitive market for health insurance coverage. Health insurers, called "hospital associations," were found to have engaged individually in cost-control efforts similar to, but possibly more aggressive than, today's utilization review under professional sponsorship. The subsequent disappearance of these insurer-initiated cost controls in Oregon is traced to the medical society's organization of a competing Blue Shield plan as a model of insurer conduct and to a simultaneous boycott by physicians of the hospital associations as long as they persisted in questioning doctors' practices. Some modern parallels are noted, and the advantages of fostering privately sponsored cost-control efforts are suggested.


Cytological differentiation and sexual isolation between populations of Drosophila nigricruria.

Drosophila nigricruria has a distribution ranging from northern Mexico to Chile. It is a relatively rare species, primarily limited to cactus deserts or pine-oak associations at altitudes of 1200 to 2100 meters above sea level. The species comprises two cytological races with a zone of hybridization in the Oaxaca and Puebla regions of Mexico. Despite the zone of hybridization, gene flow for chromosome 4 genes is limited, or non-existent, between the two races. Sexual isolation tests were run using a population from the northern race, a hybrid population, and a population that is essentially southern. Sexual discrimination among these strains was on the same order of magnitude as that found between geographical populations of other species. There was no evidence to indicate that sexual isolation is any stronger between the cytological races of nigricruria than one might expect between any two geographical populations within a species.


X-monosomy in the Indian black rat.

The south Indian black rat, Rattus r. rufescens (Gray) has a diploid number of 38 chromosomes. A random sample from Hinakal (Mysore, S.W. India) revealed the presence of rats with aneuploid chromosome numbers, viz. 2n = 37, 39, 40, and 42. The 37-chromosome individual was a female and possessed the XO constitution. The diploid numbers higher than 38 were due to the presence of supernumerary (B) chromosomes. The origin and consequences of the XO condition in Rattus r. rufescens and other mammals is discussed.


Studies on tail length of Rambouillet and Mouflon sheep.

Data are presented on tail length of various breeds or crosses of sheep and various combinations of Mouflon X Rambouillet breeding. Mouflons sheep had 11 coccygeal vertebrae, and Rambouillet had 18-24. Others were intermediate between these types. Finewool sheep (Merino or Rambouillet) had longer tails than medium wool (Dorset, Suffolk or Hampshire), crossed, or Rambouillet breeds. Heritability estimates for tail length of Rambouillet were 0.387 (intra-sire regression), 0.344 (half-sib method), and 0.706 for inter se matings in a population containing some Mouflon breeding. In the Rambouillet breed, tail length was shown to be correlated with various measures of wool production. However, this relationship was low and only wool covering and staple length were significant. The significance of this to the development of long tails in animals under domestication is discussed.


Chromosomal and allozymic diagnosis of three species of Drosophila. Drosophila pseudoobscura, D. persimilis, and D. miranda.

Techniques are presented for distinguishing the sibling species D. pseudoobscura, D. persimilis, and D. miranda in two ways: by differences in the banding sequence of salivary chromosomes, and by the frequencies of allozymes at certain diagnostic loci.


Isozymes of Culex p. fatigans. I. An esterase locus in linkage group III and its variability in natural populations.

Acrylamide gel electrophoresis revealed 19 frequent and 4 rare sites of esterase activity in various Brazilian populations of Culex p. fatigans. One pair of allozymes designated as Est-1 F and Est-1 S was selected for detailed investigation. Est-1 locus shows independent assortment from linkage group I marker, sex, and linkage group II markers, yellow and ruby, and therefore is assigned to linkage group III. Gene frequencies of Est-1 F varied from 0.49 to 0.92 in various Brazilian populations. Inhibition studies suggest that Est-1 F and Est-1 S are ali-esterases.


Inhibition of complement by mouse serum: selective inactivation of the fourth component of human complement.

Bound human C4b on EAC4 is rapidly inactivated in the presence of murine serum reagents. The functional characteristics of this inactivation suggest that it is probably caused by factor(s) homologous to human C3bI-C4bI: inactivation is temperature-dependent and occurs without concomitant consumption of the inactivator(s); loss of hemolytic function is associated with the cleavage of the bound C4b into C4c, which is released, and C4d, which is retained on the cell membrane. Murine serum reagents inhibit bound human C4b far more efficiently than C3b and may therefore be employed to selectively inhibit C4b.


Neutrophil aggregation and swelling induced by chemotactic agents.

An assay is described for measuring neutrophil aggregation and cell size with a Coulter Counter equipped with a mean cell volume computer and volume channalyzer. With this assay, it was found that several chemotactically active agents rapidly induce rabbit peritoneal polymorphonuclear neutrophils in suspension to aggregate reversibly. The aggregating activities of these chemotactic agents paralleled their in vitro chemotactic- and in vivo neutropenia-inducing potencies. Neutrophil aggregation may underlie the neutropenia which follows the infusion of these agents into rabbits. Chemotactic agents may also induce polymorphonuclear neutrophils to increase in volume; this effect appears to be independent of aggregation. The volume change develops more slowly and does not appear reversible under the conditions employed. The volume increase may be an expression of pseudopodia formation and membrane ruffling known to develop in neutrophils exposed to chemotactic agents.


Modification of fetal immune system by maternal anti-DNA antibody. I. Enhanced immune response to DNA in the mice exposed to anti-DNA antibody early in life.

The offspring mice of C3H/He strain whose mothers had been immunized with DNA or passively administered anti-DNA antibody showed enhanced ability to respond to DNA stimulation (3-fold increase in the amount of serum anti-DNA antibody and in the number of anti-DNA antibody-forming cells). The acquisition of the enhanced immune responsiveness to DNA in the offspring was most likely mediated by passively transmitted maternal antibody, not by such other factors as concomitantly transmitted antigen, carrier protein, and adjuvant. The effect of maternal antibody to carrier protein and the possible involvement of maternal lymphocytes transmitted to the progeny were also excluded. This phenomenon was observed in the mice after the transmitted antibody had been removed from them, distinguishing the effect of antibody in fetal and/or neonatal period from the regulatory effect of antibody in adult animals. The effect of maternal antibody was antigen specific. Maternal antibody might in some way modify the clonal development of fetal immune-responding cells.


Regulation of cytotoxic lymphocyte responses in vitro by alloantigen-activated spleen cells.

Spleen cells obtained from BALB/c mice 4 days after allosensitization to C57BL/6 spleen cells via footpad injection suppressed the in vitro generation of BALB/c cytotoxic lymphocytes (CL) against C57BL/6 spleen cells in mixed leukocyte cultures (MLC). Suppressor activity was demonstrated by spleen cells at 4 and 7 days but not at 2, 10, or 14 days after allosensitization and was abolished by treatment with anti-Thy-1,2 serum and complement. A weak and transient cytotoxic response directed against the sensitizing alloantigen was associated with suppressor spleen cell populations, but was dissociated from suppressor function by two experimental approaches. First, increasing stimulatory cell concentration in MLC did not competitively diminish the suppressor activity; rather, the magnitude of suppression increased as the stimulatory cell concentration was increased. Second. BALB/c suppressor cells generated in vivo by either H-2b or H-2k alloantigens suppressed CL responses generated simultaneously against both alloantigens in vitro. CL responses generated against one or the other H-2 haplotype in vitro were suppressed only by suppressor cells activated by that haplotype. Therefore, splenic suppressor cells activated by alloantigen in vivo required antigen-specific restimulation in vitro; thereafter, responder cells syngeneic with the suppressor cell were rendered hyporesponsive to alloantigens by an antigen-nonspecific mechanism.


Soluble factors in tolerance and contact sensitivity to 2,4-dinitrofluorobenzene in mice. I. Suppression of contact sensitivity by soluble suppressor factor released in vitro by lymph node cell populations containing specific suppressor cells.

Tolerance to 2,4-dinitrofluorobenzene (DNFB) contact sensitivity is in part mediated by suppressor thymus-derived cells (T cells) which are induced by pretreatment with the hapten 2,4-dinitrobenzenesulfonate. If lymph node cell suspensions containing suppressor cells are cultured in vitro, soluble suppressor factor (SSF) is released into the supernatant. When DNFB-immune lymph node cells are incubated with SSF, their ability to transfer contact sensitivity to normal recipients is suppressed. In order for SSF to be produced and/or released, it was necessary to paint the tolerant animals with DNFB 16 to 20 hr before the lymph node cells were cultured, suggesting that SSF was made in response to antigen stimulation. Specificity studies showed that SSF was both antigen specific and strain specific in its action. In addition, it was found that SSF could be absorbed by 2,4-dinitrophenyl-keyhold limpet hemocyanin (DNP-KLH) (not by KLH alone) and by anti-H-2 antibodies but not by trinitrophenyl-KLH, anti-immunoglobulin, or anti-DNP antibodies. Taken together, these results indicate that SSF is a product of the major histocompatibility complex which, although not antibody, has affinity and specificity for the hapten DNP. Furthermore, in order for SSF to suppress DNFB sensitivity, identity is required among genes in the H-2 complex between the donor of SSF and the immune lymph node cells.


Human factor D of the alternative complement pathway: purification and characterization.

D was purified to homogeneity from outdated human plasma by successive chromatography on Bio Rex 70, Sephadex G-200, Bio Rex 70, and Sephadex G-75. Column fractions were monitored for D activity by a hemolytic diffusion plate assay. The overall yield was approximately 4% by activity. A m.w. of 22,900 daltons was established by sedimentation equilibrium. Amino acid analyses have been obtained and Isoleucine has been determined as the NH2-terminus. Incubation of D with purified B and CoVF in the presence of Mg++ resulted in cleavage of B, as judged by SDS-polyacrylamide gel electrophoresis and immunoelectrophoresis. D hydrolyzed certain synthetic amino acid esters of arginine, lysine, and tyrosine. Benzoyl-L-arginine methyl esters (BAME) was the most sensitive substrate for D among those tested. The substrate profile of D was dinstinct when compared to that of CIs, CIr, plasmin, urokinase, and trypsin. Both the enzymatic and hemolytic activity of D were irreversibly inhibited by treatment with 10 mM DFP as well as by reduction and alkylation.


Isolation of the cytoplasmic granules of guinea pig basophilic leukocytes: identification of esterase and protease activities.

Procedures were developed for isolating highly purified cytoplasmic granules of basophilic leukocytes from guinea pig peripheral blood. The methods involved disruption of cells in 0.34 M sucrose followed by a series of membrane filtrations and fractionation on sucrose density gradients. These preparations, up to 95% pure basophil granules by electron microscopy, contained a mixture of neutral esterases-proteases including caseinolytic activity; both trypsin- and chymotrypsin-like serine hydrolases were identified by means of appropriate inhibitors. Localization of at least one such activity to the basophil granule was confirmed by a cytochemical method; this activity was absent in contaminating lymphocytes and eosinophils. By contrast, several lysosomal enzymes, lactic dehydrogenase, and plasminogen activator activity, present in cell homogenates, were absent from purified granules. The granule matrix of guinea pig basophils, unlike the cytoplasmic granules of other granulocytes or mast cells, was little altered by high or low salt concentration but was disrupted into insoluble fragments by 0.01 N HCl and by Triton X-100. Granules were solubilized by papain and by urea-SDS but enzyme activity was destroyed. Triton X-100 incubation with freeze-thawing proved to be the optimal method for extracting esterase activities. Esterase activities were not released from basophils under conditions of anaphylactic degranulation that liberated the great majority of basophil granule histamine.


Human cell-mediated immunity to tuberculin as assayed by the agarose micro-droplet leukocyte migration inhibition technique: comparison with the capillary tube assay.

Direct and indirect agarose microdroplet migration inhibition assays were performed with log dilutions (50--5 X 10(-8) microgram/ml) of soluble purified protein derivative (PPD) of tuberculin and leukocytes (4 X 10(5)/droplet) from PPD skin test positive or negative individuals. Some tests were run in parallel with the capillary tube method. Inhibition of migration of leukocytes from 9/11 PPD skin test positive donors studied was observed in direct tests when employing PPD doses ranging from 1--50 microgram/ml PPD. Inhibition of migration of leukocytes from some PPD skin reactive donors was obtained with as little as 5 X 10(-3)--5 X 10(-7) microgram/ml (i.e., 5 nanograms to 0.5 picograms). Some inhibition of leukocyte migration was seen with skin test negative donors (presumably toxicity) with the higher doses of PPD (50 microgram/ml), but generally little inhibition was observed with these donors at lower doses. Comparative experimetns of the agarose micromethod and the capillary tube technique indicated that the agarose assay was more sensitive in that it could detect reactivity with 2--4 logs lower antigen concentration. Indirect assays using supernatants of cultures of PPD triggered mononuclear cells and indicator granulocytes in agarose droplets demonstrating that a lymphokine (presumable leukocyte inhibitory factor) was being produced and suggested that cell-mediate immune (CMI) reactions were operative. The results indicate the usefulness of this technique in the sensitive-detection of CMI against such antigens as soluble PPD. The assay should prove useful in quantitative assessment of cell-mediated reactivity by using a wide range of antigen concentrations and the leukocytes from as little as 2--5 ml of blood.


Multiple foreign non-H-2 determinants on the surface of a chemically-induced murine sarcoma.

By immunizing BALF/c (H-2d) mice against normal tissues from C57BL/6J (H-2d), C3Hf (H-2k) and DBA/2 (H-2d), but not from AKR (H-2k) strains, resistance was induced to the subsequent challenge of the 'syngeneic' methyl-cholanthrene-induced BALB/c sarcoma ST5; lymph node cells from alloimmune BALB/c mice were also able to exert a parallel cytotoxic effect against in vitro cultured ST5 cells. The involvement of foreign H-2 specificities in the observed cross-reactions was ruled out by absorption of H-2 monospecific sera and by the interallelic combinations used, thus suggesting that non-H-2 histocompatibility antigens were responsible for the above findings. By using the indirect isotopic antiglobulin assay, BALF/c anti-C57BL/6J and anti-C3Hf polyspecific sera were found to bind specifically to cultured ST5 cells. C57BL/6J and C3Hf, but not DBA/2, lymph node cells were able to absorb the anti-ST5 activity of the anti-C57BL/6J serum. These results indicated that ST5 cells expressed on their surface at least two different sets of foreign non-H-2 antigens: one shared by C57BL/6J and C3Hf tissues, and detected by both cell-mediated and serological techniques; the other one belonging to DBA/2 tissues, and revealed mainly at the cell-mediated level.


Effects of local anesthetics on tactile sensitivity thresholds for cutaneous and mucous membranes.

New, reliable, and precise methods for measuring absolute pressure sensitivity in mucous membranes and on intact skin are described. Studies were conducted to determine how local anesthetics (phenol and sodium phenolate and Benzocaine) affect tactile sensitivity thresholds in the oropharynx and on the intact skin of the volar surface of the forearms, ankles, knees, elbows, and dorsum of the hands. Gargling and expectorating a solution containing phenol had a significantly greater anesthetic effect on the mucous membranes of the oropharynx than spraying and swallowing, which, in turn, had a greater effect than drinking the solution. Compared with ethanol and petroleum jelly (Vaseline), the topical application of Benzocaine (0, .5, 1, 3, and 5% solutions in 100% ethanol) significantly increased the tactile sensory thresholds on the volar surface of the forearm. A highly significant loss of tactual sensitivity of the oropharynx was demonstrated in smokers.


A key to the classification of cutaneous mechanoreceptors.

The cutaneous mechanoreceptors of the cat can be assigned to one of 11 groups by using physiologic tests performed with hand-held stimulators. The method of classification is described, and the validity and utility of this classification scheme are discussed.


Cytochrome P-450 content and mixed-function oxidation by microsomes from rabbit alveolar macrophages.

Cytochrome P-450 content and p-nitroanisole demethylation (a mixed-function oxidation) were investigated in the microsomal fraction from rabbit alveolar macrophages. The content of cytochrome P-450 was 0.13 +/- 0.024 (mean +/- S.E., n = 9) nmol/mg protein and was not stimulated by pretreatment of rabbits with chlorpromazine. Pretreatment with BCG resulted in decreased cytochrome P-450-specific content, suggesting that the microsomal protein pool was diluted by de novo synthesis of noncytochrome proteins. Demethylation of p-nitroanisole by alveolar macrophage microsomes during a 1 hr incubation was 17.1 +/- 1.4 nmol X hr-1 X mg protein-1. The microsomal fraction from homogenates of whole lungs had a cytochrome P-450 content of 0.32 +/- 0.078 nmol/mg protein and p-nitroanisole demethylase activity of 26.6 +/- 8.7 nmol X hr-1 X mg protein-1. The results indicate the presence of cytochrome P-450 in rabbit alveolar macrophages and show that the microsomal fraction can catalyze a mixed-function oxidation reaction. Comparison of alveolar macrophage and whole lung microsomal preparations indicates that alveolar macrophage cytochrome P-450 comprises a minor fraction of the total pulmonary pool.


A rapid, inexpensive, infrared screening method for elevated serum triglycerides.

The application of infrared absorption spectrophotometry to the mass screening of human serum for elevated triglyceride levels has been investigated, and results in both normal and elevated ranges have been compared with values obtained by manual and automated procedures. By means of a simple technique serum samples were scanned with a typical instrument, and the difference in absorbance at 1,740 and 1,725 cm-1 was plotted vs. triglyceride concentration to prepare a Beer-Lambert plot; several hundren serum samples were then determined with the plot, and results were compared with those from two independent methods with good agreement. Significantly elevated serum cholesterol ester levels gave high values, but this was not considered a disadvantage in view of the general screening nature of the determination. The standard deviation at 160 mg/dl was found to be 13. The infrared method is presented at a viable mass screening procedure; it is not proposed that it supplant presently available laboratory procedures for routine use at this time. Advantages of the infrared method include simplicity, rapidity, low supply cost per test, and small sample volume.


Adaptation of TSH filter paper method for regionalized screening for congenital hypothyroidism.

A sensitive, specific, rapid radioimmunoassay is described for the determination of thyrotropin (TSH) in eluates from two 3 mm discs punched from dried blood filter-paper specimens. This method is sufficiently sensitive to easily discriminate between normal infants and infants with primary hypothyroidism. The use of two 3 mm discs enables screening laboratories to easily incorporate this methodology into the currently available, fully automated systems to screen for several metabolic disorders. Since mental retardation occurs in untreated infants with primary hypothyroidism, our TSH method as the primary screening test alone, or in association with a thyroxine (T4) screening test, should detect all infants with primary hypothyroidism with a very acceptable low false-positive recall rate.


The role of RNA metabolism in polymorphonuclear leukocyte phagocytosis.

The role of RNA metabolism in human PMN phagocytosis was examined. By the inhibition of RNA synthesis with actinomycin D, intracellular killing of a strain of actinomycin D-resistant S. epidermidis was unaffected by 1 hr but significantly decreased by 2 and 3 hr. After 1 hr, phagocytosis began to decrease, and iodination of proteins also decreased in the presence of actinomycin D. Hexosemonophosphate shunt activity remained similar for both actinomycin D treated PMN's and control cells at 30 min and 2 hr. Protein synthesis was inhibited by incubating PMN's with puromycin. The ability of the PMN's to kill puromycin-resistant S. epidermidis was significantly decreased at 2 and 3 hr.


The lumi-aggregometer: a new instrument for simultaneous measurement of secretion and aggregation by platelets.

We have developed a new instrument that simultaneously monitors aggregation and secretion of ATP from the same sample of platelets. Aggregation is determined by the usual turbidimetric method; secretion of ATP is followed by measuring luminescence from the firefly luciferase system at right angles to the aggregometer light path. Data are recorded on a two-pen strip chart recorder and reveal the temporal relations between the two platelet responses.


Biological behavior of higher molecular weight products of fibrinolysis.

We have examined the consequence of infusions into rabbits of the products of limited plasmin hydrolysis of fibrin (early fibrin degradation products, or early fdp) containing defined quantities of fibrin fragment X. For comparison, early fibrinogen degradation products (early FDP) and late fibrin degradation products (late fdp) consisting almost exclusively of core fragments D and E were infused into separate groups of animals. Components of early fdp, probably fibrin fragment X, behaved in many respects like fibrin monomer. Infused unlabeled early fdp produced circulating soluble fibrin complexes with 125I-labeled fibrinogen. 125I-labeled early fdp rapidly accumulated in the spleen and liver and also to a significant degree in the lungs as insoluble, nonextractable tissue-bound protein; in contrast, only minimal quantities of early FDP and late fdp accumulated in organs. When 125I-labeled early fdp were administered to animals given continuous infusions of epsilon-aminocaproic acid to block fibrinolysis, substantial amounts of radioisotope also accumulated in the kidneys. These observations suggest a possible pathophysiological role for the products of lysing fibrin encountered in clinical states associated with disseminated intravascular coagulation.


Electrophoretic variation in the partial deficiency of hypoxanthine-guanine phosphoribosyltransferase.

Mutant hypoxanthine-guanine phosphoribosyltransferase from four patients with a partial deficiency of this enzyme has been studied by isoelectric focusing. The isoenzymes found in these hemolysates were different from the normal isoenzymes and were different from each other. These observations suggest that electrophoretic variation is a common occurrence in this disorder and they support the existence of structural gene mutations with genetic heterogeneity in this X-linked hyperuricemia.


Use of breath hydrogen (H2) to quantitate small bowel transit time following partial gastrectomy.

The relation between small intestinal transit time and postgastrectomy diarrhea was investigated with a technique which employs the measurement of pulmonary H2 excretion after ingestion of the nonabsorbable sugar, lactulose. Ten postgastrectomy patients with persistent diarrhea had an average small bowel transit time of 35.2 +/- 3 min (S.E.M.), which was significantly (p less than 0.05) shorter than either that of 10 patients without diarrhea (74.6 +/- 5 min) or 40 healthy controls (72.6 +/- 5 min). These decreased transit times appeared to be due to rapid gastric emptying rather than to a primary intestinal abnormality, since the transit of lactulose instilled directly into the jejunum was equally rapid in patients and controls. All postgastrectomy patients with diarrhea failed to absorb a portion of a 100 gm dose of glucose (quantitated by pulmonary H2 measurements), but all patients without diarrhea and 10 healthy control subjects absorbed the entire dose. Constant perfusion studies of the terminal ileum in two patients indicated that glucose absorption was least efficient from the most rapidly moving front of the ingested bolus of glucose. These studies suggest that the diarrhea observed in some postgastrectomy patients is, in part, the result of malabsorption of carbohydrate due to excessively rapid small bowel transit which is secondary to rapid gastric emptying.


Digital blood pressure monitoring in critical care and dialysis patients.

We describe a new technique for determining blood pressure in intensive care and dialysis patients in whom the routine antecubital pressure measurements are difficult to obtain or interpret. The method utilizes a Doppler instrument to monitor digital blood pressure.


Ferritin distribution and synthesis in sex-linked anemia.

The ferritin concentration of duodenum, liver, and spleen and the incorporation of L-leucine-3H into immunoprecipitated duodenal and liver ferritin was measured in genotypically normal (+/Y) mice and mice with sex-linked anemia (sla/Y), an X-linked recessive trait determined by a defect in intestinal iron absorption. Liver and splenic ferritin concentration was lower in sla/Y animals than in +/Y animals. Parenteral iron administration produced an increase in the duodenal, liver, and splenic ferritin concentration in both sla/Y and +/Y animals that was most striking in the case of the liver. Duodenal ferritin synthesis, both in vivo and in vitro, was increased in iron-deficient sla/Y animals and decreased in iron-deficient +/Y animals. In contrast, liver ferritin synthesis was decreased in both sla/Y and +/Y iron-deficient animals. In sla/Y animals fed an iron-deficient diet, duodenal ferritin synthesis decreased to near normal levels. These results indicating a high level of duodenal ferritin synthesis in standard-fed mice with sex-linked anemia suggest that the primary genetic defect is more likely a disorder of intramucosal iron transport than a primary disturbance of ferritin metabolism.


Estrogen suppression of surgically induced vascular intimal hyperplasia in rabbits.

Since estrogen has been shown to reduce aortic medial hypertrophy in hypertensive rats, a naturally occurring estrogen compound, estradiol, was studied for its ability to suppress the intimal hyperplasia which follows vessel transection and anastomosis. Suture lines and adjacent abdominal aortas were examined by light and electron microscopy 1 month after surgery, in 23 rabbits. Test animals were given 200 microgram of Depoestradiol I.M. weekly, starting 3 days preoperatively. Control animals were similarly manipulated but received no estrogen. Control animals showed striking intimal thickening over the sutures, in contrast to the estrogen-treated group in which there was significantly less growth of corresponding tissue (p less than 0.01).


Radiation therapy of squamous carcinoma of the floor of mouth and the lower alveolar ridge.

Treatment for 139 patients with squamous carcinomas in the floor of mouth and the lower alveolar ridge, which accounted for one-third of all patients with intra-oral cancer, are evaluated and classified after UICC and AJC's TNM recommendations retrospectively, for cancer staging and End Result Reporting. The figures include 50% women with tumours and in lower alveolar ridge. Two treatment schemes: external cobalt irradiation and external irradiation in combination with intra-oral radium-mould have been used in spite of primary bone invasion. 30% had remnant tumours and 22% recurred locally. 70% of the recurrences were discovered within a year after treatment. The total crude survival for all patients was 32%, identical for both groups. Lymph node metastases lower the survival significantly. Less than one-third had difficulties in mucous healing after treatment and 9% developed osteoradionecrosis, but only half of those patients had symptoms.


Profound bilateral sensorineural hearing loss during gentamicin therapy.

A case of profound bilateral sensorineural deafness occurring during gentamicin therapy is presented. Considerable recovery of the hearing in the right ear was observed but the left ear remained "dead". Electrocochleography confirmed the end-organ nature of the damage. Apart from the profound sudden deafness the unusual feature of this case was the total absence of vestibular effects. The ototoxic effects of gentamicin are discussed including the predisposing factors. While the incidence of ototoxicity with gentamicin is low (2-3%) this figure will only remain acceptable if the use of the drug is restricted to those patients who might die or suffer severe morbidity without it. The factors which make side-effects more likely to occur should always be borne in mind and due attention paid to the monitoring of renal function and serum antibiotic levels.


Cervical angiofollicular lymph node hyperplasia (lymphoid hamartoma).

A case of the hyaline vascular type of angiofollicular lymph node hyperplasia (lymphoid hamartoma) in the neck of a 25-year-old Hindu male is reported. A brief review of the literature is presented and relevant clinical, pathological and therapeutic aspects of this lesion are discussed.


Influence of foetal genotype on the follicle-stimulating hormone:luteinizing hormone ratio of pregnant mare serum gonadotrophin.

Rat testicular radioreceptor assays specific for FSH and LH were used to determine the FSH:LH ratio of PMSG produced by horse, donkey, mule and hinny conceptuses. Measurements of FSH and LH activities in PMSG produced both in vivo and in vitro by the four types of conceptuses showed that the genotype of the foetus markedly influences the FSH:LH ratio of PMSG. The FSH:LH ratio of PMSG produced by the horse conceptus was around unity whereas the ratio of PMSG produced by the donkey conceptus was as low as 0-2. Furthermore, the hybrid mule and hinny conceptuses both produced PMSG with an FSH:LH ratio which was approximately midway between those of the horse and donkey.


Steroid synthesis in vitro by the placenta of the guinea-pig, and progesterone concentrations in systemic and uterine plasma.

The spongy zone (SZ) syncytiotrophoblast has been identified as the prinicipal site of progesterone synthesis in the placenta of the guinea-pig. This was evident from the relatively large amounts of progesterone synthesized by the SZ from [7alpha-3H]pregnenolone and the exact correlation of SZ development and the estimated progesterone secretory activity of the placenta throughout gestation. Placental progesterone secretion started between days 20--25 of gestation when the SZ was being formed. Progesterone secretion rose to a maximum by day 30 and was maintained until at least day 53, reflecting the large amount of SZ tissue present in the placenta during this period. Secretory activity decreased simultaneously with decrease in SZ tissue, even though a decrease in progesterone concentration in systemic plasma was not evident. The results also suggested that the yolk sac was able to synthesize progesterone and metabolize steroids in vitro. Small quantities of 5-saturated C21 steroids were also synthesized by the placenta.


Impairment of the control of gonadotrophin secretion after oestrogen administration to adult female rats.

The possible occurrence of long-term changes in gonadotrophin control mechanisms following the administration of oestrogen to adult female rats has been studied. Administration of 2-5 mg oestradiol benzoate (OB) to normal female rats at 60 days of age did not result in failure of ovulation at 120 days of age but significant impairment of the LH and FSH responses to progesterone after ovariectomy and oestrogen priming was observed at 160-180 days of age. Treatment with the same dose of OB at 60 days of rats injected with 10 microgram testosterone propionate on Day 4 of postnatal life resulted in an increased incidence of failure of ovulation at 120 though not at 150 days of age but did not further impair the already reduced gonadotrophin response to progesterone at 160-180 days of age. Removal of the ovaries at 60 days of age did not modify the effects of oestrogen given at 60 days of age in either group nor did ovariectomy at 60 days improve the response of neonatally androgen-treated rats to progesterone at 160-180 days of age. The increases in plasma prolactin and TSH levels in response to oestrogen priming after ovariectomy were not affected in any of the experimental groups. The administration of a long-acting oestrogen preparation (oestradiol cyclopentyl propionate, 2-5 mg at 60 days of age) to normal female rats suppressed ovulation and depressed plasma LH and FSH concentrations for at least 90 days; anterior pituitary weights were greatly increased and plasma prolactin concentrations were very high.


Analysis of androgen-binding protein in media from sertoli cell incubations and cytosols from rat testes.

Binding ability of androgen-binding protein (ABP) in concentrated media from Setoli cell cultures and in various preparations of cytosols from rat testicular tissue have been estimated using dialysis and polyacrylamide gel electrophoresis (PAGE). Equilibrium dialysis in the presence of 1 nM-17beta-hydroxy-5alpha-androstan-3-one appears to be the most convenient and reliable method for estimation of ABP if no other binding proteins are present. PAGE can be applied for estimation of ABP in samples which also contain other steroid-binding proteins. Estimated binding activities in culture media measured by PAGE and dialysis were essentially similar. Binding of androgens to ABP estimated with PAGE in cytosols prepared after sonication of testicular tissue was much lower than in cytosols obtained after homogenization using a Potter-Elvehjem homogenizer. When ABP was added to cytosols prepared after sonication or homogenization, approximately 50 and 90% respectively of the original binding of androgens to ABP was recovered.


Effect of hypophysectomy on p-aminohippurate transport kinetics in rat renal cortical slices.

Recent work on kidneys from hypophysectomized (hypox) rats has shown atrophy of the proximal tubules with no effects on the other parts of the nephron. We carried out experiments to determine whether the reduction of p-aminohippurate (PAH) is consistent with structural changes in the proximal tubule of hypophysectomized rats. Initial velocities of PAH uptake by renal cortical slices were found to be constant over 30 min of incubation at concentrations of PAH up to 0-5 mmol/1 for both control and hypox animals. Using kinetic analysis, it was found that both maximal velocity, Vmax, and the Michaelis constant, Km, were reduced in hypox animals, the relative reduction being similar for both parameters. Comparison between high Na (100 mmol/1) and low Na (6 mmol/1) media indicated that in both control and hypox rats, Vmax was significantly lower in low Na medium than in high Na medium, whereas Km was not changed. Efflux of PAH from pre-loaded tissue also showed a reduction in hypox animals. These results may indicate that hypophysectomy alters the capacity of PAH transport in renal cortical slices by (1) reducing the effective transport area or sites, and (2) by changing carrier-substrate affinity.


A phylogenetic study of sulphation factor activity in 26 species.

Somatomedin (sulphation factor) activity was measured in 26 species by a porcine cartilage bioassay. Although non-dialysable inhibitory factors were present in many species, sulphation factor activity was present in the sera of all the vertebrates studied but was absent from the invertebrates.


Plasma renin activity and blood corticosteroids in the Australian lungfish Neoceratodus forsteri.

Plasma renin activity (PRA) and blood aldosterone and deoxycorticosterone levels were measured in Australian lungfish. Plasma renin activity was depressed after intravenous infusions of iso-osmotic (0-6%) NaCl but not after hypo-osmotic (0-3%) infusions. The presence of PRA in this fish is consistent with prior reports of renal renin activity in other sarcopterygian fishes. The results of the infusion experiments suggest that a fall in plasma osmolality or electrolyte concentrations may oppose the reduction in renin release in response to volume expansion. Aldosterone and deoxycorticosterone were identified in the blood of Neoceratodus. The concentrations of both appeared higher in females than in males. Infusions of [5-valine]-angiotensin II amide for 2-4 h at rates known to increase blood pressure in this species did not alter blood aldosterone concentrations. This negative finding may suggest that the renin/angiotensin system is not involved in aldosterone regulation in Neoceratodus or that angiotensin receptors involved in regulation of steroidogenesis have a greater specificity for endogenous angiotensin than do vascular receptors.


Induction of the rat prostate gland by androgens in organ culture.

The induction of the prostate gland by testosterone or dihydrotestosterone was studied in urogenital sinuses from Wistar rat embryos explanted in organ culture. In normal development, prostatic rudiments appeared in the urogenital sinuses of 18-19 day male foetuses as epithelial buds projecting into the mesenchyme. Male urogenital sinuses from 17-5 and 18-5 day foetuses formed buds in control medium, and addition of testosterone or dihydrotestosterone increased their number and size. In contrast, sinuses from 15-5 and 16-5 day male foetuses did not form buds in the absence of androgens, while exposure to the hormones induced them de novo. A concentration of 0-0015 microgram testosterone/ml was sufficient to elicit prostatic buds. The same effect was seen after continuous treatment with testosterone or brief exposure to the hormone followed by cultivation in control medium. The development of the buds followed the same time sequence as in the organ in  situ. Testosterone and dihydrotestosterone elicited prostatic buds in female sinuses from 15-5 to 18-5 day foetuses, but their response to androgens decreased with advancing foetal age. Male and female sinuses from 15-5 day foetuses did not respond to testosterone but formed buds after exposure to dihydrotestosterone. This difference was considered to be due to a low content or absence of 5alpha-reductase at this stage. Testes from 15-5 to 18-5 day foetuses grown in close contact with urogenital sinuses or explants of mature prostate glands induced prostatic buds or augmented the height of the prostatic epithelium. It was concluded that androgens are necessary for the initiation of the rat prostate gland and that the effect of testosterone is mediated via 5alpha-dihydrotestosterone. The onset of 5alpha-reductase synthesis is likely to occur between days 14 and 15 of foetal life. The early androgenic activity of the testes suggests that bud formation in the older male sinuses in the absence of androgens is due to exposure to endogenous testosterone before explanation.


Desensitization of the dopaminergic inhibition of pituitary luteinizing hormone release by prolactin in ovariectomized rats.

Increase of plasma prolactin in chronically ovariectomized rats by transplanting pituitary glands from male rats to the kidney capsule reduced pituitary LH output for 1 week. At the end of this time, despite the fact that prolactin remained high, plasma LH levels rose to reach the value seen in ovariectomized control rats. High plasma prolactin did not affect FSH concentrations. Treatment of ovariectomized rats with apomorphine, a dopamine-receptor stimulating drug, reduced pituitary LH release in a dose-dependent way at doses of 1, 2, 5 and 10 mg/kg body weight. Higher doses either had no effect or they stimulated pituitary LH release. Apomorphine did not reduce pituitary LH secretion in chronically hyperprolactinaemic rats at doses which significantly inhibited LH release in ovariectomized animals. Plasma FSH levels were not affected by apomorphine treatment. In both groups of animals the drug reduced plasma prolactin levels to basal values, indicating that the dopamine agonist inhibits pituitary prolactin release by direct action on the pituitary gland. These results suggest that dopamine inhibits pituitary LH release, probably by reducing hypothalamic LH-releasing hormone release. The mechanism by which chronically high prolactin levels cause apomorphine to be less effective in reducing pituitary LH release may be a desensitization of some dopamine-receptive mechanism which is inhibitory to LH release.


Effects of testosterone, testosterone metabolites and anti-androgens on the function of the male accessory glands in the rabbit and rat.

The androgenic potencies of testosterone, 5alpha-dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol and 5alpha-androstane-3beta,17beta-diol towards the prostate, glandula seminalis+glandula vesicularis, ampullae and epididymis were evaluated after administration to castrated rabbits. The influence of cyproterone acetate, stilboestrol and medrogestone on accessory gland function was also investigated in rabbits and rats. In the rabbit it was found that the minimum dose of testosterone propionate that would maintain the function of all accessroy glands at normal levels was approximately 200 microgram/animal/day. Higher levels of testosterone propionate overstimulated the function of the prostate, glandula seminalis+glandula vesicularis and ampullae, but did not affect the epidiymis. Whereas testosterone propionate and 5alpha-dihydrotestosterone propionate were essentially equipotent in their capcity to support growth and secretory activity and stimulated all the accessory glands, 5alpha-androstane-3alpha,17beta-diol dipropionate had a pronounced differential effect; it was considerably more potent than testosterone propionate in promoting secretion in the prostate, but was ineffective in maintaining the function of the epididymis. 5alpha-Androstane-3beta,17beta-diol dipropionate was the weakest androgen tested. Evidence also indicated that the potency of a steroid can depend on whether it is administered as its free or esterified form. Cyproterone acetate suppressed fructose secretion in the prostate of the rabbit but had no adverse effects on the function of the epididymis in either the rabbit or rat. Stilboestrol was the most potent anti-androgen tested and medrogestone the least effective.


The nature of control by spoken words over visual stimulus selection.

Eight retarded adolescents were trained to select one (a trained S+) of two visual stimuli in response to a spoken word (a trained word). Two different visual stimuli alternated randomly as the S-. To determine if the spoken work was merely a temporal discriminative stimulus for when to respond, or if it also specified which visual stimulus to select, the subjects were given intermittent presentations of untrained (novel) spoken words. All subjects consistently selected the trained S+ in response to the trained spoken word and selected the previous S- in response to the untrained spoken words. It was hypothesized that the subjects were responding away from the trained S+ in response to untrained spoken words, and control by untrained spoken words would not be observed when the trained S+ was not present. The two visual S- stimuli selected on trials of untrained spoken words were presented simultaneously. The untrained spoken words presented on these trials no longer controlled stimulus selections for seven subjects. The results supported the hypothesis that previous control by spoken words was due to responding away from the trained S+ in response to untrained spoken words.


Immunity in taeniasis-cysticercosis I. Vaccination against Taenia taeniaeformis in rats using purified antigen.

Artificial immunization of rats against Taenia taeniaeformis was studied using somatic antigen (Som-Ag) and excretory-secretory antigen (ES-Ag). It was found that both Som-Ag and ES-Ag stimulated immediate-type hypersensitivity and delayed-type hypersensitivity reactions of similar levels. Antibody levels rose from the 2nd wk and peaked around the 6th and 7th wk. Both IgM and IgG were detectable from the 2nd wk onwards, with IgG at a considerably higher level compared to IgM. It terms of protection, 90-100% reduction in cyst counts were detected if the rats were challenged 10 days or more after immunization. In all cases, no significant difference was observed between immunization with either Som-Ag or ES-Ag were purified and characterized using Sephadex G-200 chromatography, double immunodiffusion, and disk acrylamide gel electrophoresis. A purified antigen (mol wt, 140,000 daltons) was obtained, and highly significant protection against infection resulted with injections of 50, 10, or 1 mug doses of this antigen with complete Freund's adjuvant.


Suppressor cells in tolerance to contact sensitivity active against hapten-syngeneic and hapten-allogeneic determinants.

Genetic restrictions in generation and expression of hapten-specific suppressor cells for contact sensitivity were found. Dinitrophenol- (DNP) or trinitrophenol-modified mouse spleen cells (SC) induced suppressors in donors able to transfer suppression to normal recipients. When allogeneic DNP-SC were injected into BALB/c mice, cells were generated which were suppressive only in the allogeneic strain providing the DNP-SC. In contrast, when DNP-BALB/c-SC were injected into BALB/c mice, suppressors were generated which were active both in BALB/c and in allogeneic mice (e.g., CBA). This apparent absence of syngeneic major histocompability complex restriction may be explained by cross reactive T-cell receptors which are VH gene products.


Activation of factor XII by tobacco glycoprotein.

A glycoprotein of mol wt ca. 18,000 daltons isolated from cured tobacco leaves (TGP-L) and from cigarette smoke condensate (TGP-CSC) activated factor XII in normal human plasma in vitro as measured by (a) shortening of the partial thromboplastin time, (b) shortening of the lysis time of euglobulin clots, and (c) generation of kinin activity. These effects were not demonstrable in plasma deficient in factor XII. The capacity of TGP-L and TGP-CSC to activate factor XII was shown to depend on the presence of rutin, a substance chemically similar to quercetin and ellagic acid, which are known activators of factor XII. Rutin and rutin coupled to bovine serum albumin, but not bovine serum albumin alone, were also demonstrated to activate factor XII. The presence in cigarette smoke of material that is both allergenic and capable of activating factor XII of the intrinsic pathway of coagulatin may be important to the pathogenesis of cardiovascular and pulmonary disease associated with cigarette smoking.


Effects of chronic illness on the family.

Chronic illness is perhaps the most common type of illness encountered by the physician in our society. The clinical management of chronic illness includes a consideration for the social, cultural, and psychological situation of the patient and his family. This paper examines some of the common effects of chronic illness on the family and indicates how the family physician can assist families in adjusting to chronic illness, which will facilitate its clinical management.


Improving communication with the deaf patient.

Deafness affects 1.8 million people in the United States. The special comminication problems of deaf people may lead to serious misunderstandings, particularly during a medical evaluation. Patients with no residual hearing usually read lips with only 40 percent accuracy. Furthermore, physicians may have great difficulty understanding the deaf patient's impaired speech and faulty written English. Underestimating the patient's intelligence, the doctor may give reassurances or oversimplified explanations. The purposes of this paper are to clarify the reasons for the speech and language problems of deaf people and to dispel some common misconceptions about deafness and sign language. Recommendations are given for improving doctor-patient communication.


Coital (cardiac) convulsions: case report of a unique presentation of complete heart block.

A 55-year-old man presented with the acute onset of seizures occurring during the post orgasmic phase of sexual intercourse. Evaluation for brain neoplasm was negative. During the hospital stay, the patient developed status epilepticus during which electrocardiogram documented complete heart block. The seizure disorder was corrected with the insertion of a permanent epicardial pacemaker.


Diagnostic perceptions and diagnostic behavior in a family practice unit.

Results of a pilot study with nine physicians in a model Family Practice Unit are described in this report. It was hypothesized that decisions regarding treatment priorities would lead to the "undertreatment" of ailments for which the physicians felt relatively ineffective and that feelings of efficacy would be greater for primarily organic than for primarily psychological ailments. Physician interviews and examination of the Unit's diagnostic file provided the data for this study. A treatment bias as a function of the degree to which an ailment had a psychological compenent was not demonstrated. However, the physicians did feel less effective (less comfortable) in treating problems that were significantly psychological and also felt that methods of intervention for such ailments were less clear-cut. Physician comfort level was greater when there were few alternative treatment methods generally used for the ailment and when the ailment was recorded frequently. A suggestion is made that medical curricula include more practical experience in treating ailments which have notable psychological components in order to increase physician comfort and probably physician effectiveness.


An operational model for teaching geriatric medicine in a family practice residency program.

Increased concern for our aging population has necessitated an evaluation of the role of gerontology and geriatric medicine in both undergraduate and graduate medical education programs. The instructional model developed for the Family Practice Residency Program at the University of Minnesota Medical School emphasizes removing barriers to health care for the aged and modifying attitudes of physicians toward normal aging. Three general components make up the Geriatric Medicine Program: (1) clinical rotations in geriatric medicine in ambulatory residential facilities, in multilevel long-term care facilities, and in an acute care hospital; (2) geriatric case conferences; and (3) a seminar in gerontology and geriatric medicine. Evaluation of these components by the residents indicates a high degree of satisfaction with the experience and belief in its applicability to future practice.


Prevention of complications in initial development of family practice residency programs.

The development of a family practice residency program involves a complex process that requires careful attention to a wide range of factors, such as educational, clinical, attitudinal, economic, and administrative. Although there are many requisites in common with all such programs, each developing program must be adapted to the particular resources and needs of its own community. The initial planning phase is perhaps the most critical period in a program's development. There are many potential pitfalls that must be avoided in starting a program, any one of which can jeopardize its accreditation and future successful operation. This paper presents a hypothetical case of a developing family practice residency program which illustrates a number of serious pitfalls. Common pitfalls are described, and ten basic principles are presented which are useful in planning and will help to prevent complications in developing programs.


A method for assessing the outcome of acute primary care.

Some 1,700 acute care episodes were studied to assess the outcomes in terms of the extent to which patients regained their usual functional status. Involving active follow-up of each patient, the study serves as a prototype for measuring several components of quality of care including actual outcomes, patient expectation of outcome, physician expectation of outcome, and patient satisfaction with outcome and care. Because this study was conducted in a family practice residency training setting, we hope that it will serve as a model of how such information may be used to increase residents' sensitivity to the course of illness commonly seen in primary care, and to encourage the residents to set expectations for the care they give.


Consultation and referral patterns of family physicians.

A one-month study of all consultations and referrals to medical specialists and other community resources made by 39 family physicians was undertaken in London, Ontario, in the spring of 1975. Eight physicians were in practice in the community and 31 were staff physicians or residents in family medical centers associated with the Department of Family Medicine of the University of Western Ontario, London. Rates of referral per 100 office visits are calculated and examined according to physician experience and location of practice. The reasons given for referral and for choosing the specific consultant or agency are also analyzed. Referral rates are compared with previous studies.


An intregrated medical record and data system for primary care. Part 2: classifications of health problems for use by family physicians.

Health problems encountered in the ambulatory setting differ from those of hospitalized individuals. For that reason disease classifications of morbidity devised for inpatient categorization are not totally applicable in the ambulatory setting. Numerous classification systems have been devised to overcome this discrepancy and have enjoyed varying levels of success. The International Classification of Health Problems in Primary Care (ICHPPC) is one of the more useful for family physicians and other primary care physicians. Its hierarchical structure and compatibility with the International Classification of Diseases (ICD) permits comparative use. The history, characteristics, and uses of ICHPPC are discussed as are those of additional classification systems recently developed for other purposes. One of these, a classification of performed procedures, may be used in conjunction with ICHPPC to provide a useful record for the provider as well as facilitating the referral of health-care information to third-party payors.


Ultrastructural analysis of gene interaction and melanosome differentiation in the retinal pigment cells of the albino goldfish.

The genotype of albino goldfish is represented by pp,cc, and the non-albino fish is PP,CC. The P gene begins to control the melanosome formation of retinal pigment cells at St-21; and the C, which is epistatic to P and p, governs melanosome formation in the dermal melanophores and in retinal pigment cells after St-22. Then  in the pp,CC fish, between St-21 and St-22, melanosomes of the pigmented retina are albino in type, but after St-22 they become non-albino in type. From ultrastructural observations on the melanosomes of these late-melanizing fish, it is apparent that the imcompletely melanized albino pigment granules can differentiate into normal melanosomes under the control of the C gene. The processes of melanosome maturation in the late-melanizing goldfish are evident from these observations.


Pituitary enhancement of Wolffian lens regeneration in vitro: spatial and temporal requirements.

When irido-corneal complexes (ICC's) from eyes of adult newts (Notophthalmus viridescens) are cultured on top of pituitary glands they produce advanced lens regenerates in up to 90% of the cases (this report and Connelly et al., '73). To determine if the iris and pituitary gland must be in direct contact with each other in order to produce this enhancement of lens regeneration, ICC's were cultured next to pituitary glands or separated from them by a Nuclepore filter. Cultures behaved as ICC's cultured in the absence of the pituitary gland and produced few advanced lens regenerates. To determine how long the iris and pituitary must be in contact for the enhancement to occur, ICC's were explanted and 5, 10 or 15 days later pituitary glands were placed beneath the dorsal iris pupillary margin. There was a progressive decrease in the number of advanced lens regenerates formed in cultures receiving pituitary glands later than five days after initial explantation of the iris. The conclusions drawn from these experiments are that the iris and pituitary gland must be in extensive direct contact during the first five to ten days in culture in order for pronounced enhancement of lens regeneration to occur.


A radioresistant Gram-positive asporogenous rod isolated from the faeces of a giant panda (Ailuropoda melanoleuca).

A highly radioresistant bacterium was isolated from the faeces of a giant panda (Ailuropoda melanoleuca). When the organism was subjected to gamma irradiation in phosphate buffer, the induction dose and D10 values were 846 and 345 krad, respectively, for cells grown on PCNZ agar, and 700 and 460 krad, respectively, for the enlarged cells grown on 5% (v/v) horse blood brain heart infusion agar. The D10 value of the former cells was about 1.8 times higher than that of Micrococcus radiodurans grown on PCNZ agar.


The actinomycete-genus Rhodococcus: a home for the "rhodochrous" complex.

A numerical taxonomic classification study was carried out on 177 strains representing the "rhodochrous" complex and the genera Gordona, Mycobacterium and Nocardia. The strains were examined for 92 unit characters and the data were analysed by computer. Three clusters were defined at the 75 to 80% similarity level. The first was a heterogeneous cluster corresponding to the "rhodochrous" taxon whereas the other two contained Mycobacterium and Nocardia strains respectively. The good correlation between the numerical analysis and chemo-taxonomic, serological and genetical data collected from previous studies provides sufficient evidence for raising the "rhodochrous" taxon to generic status. We consider the generic name Rhodococcus Aopf to have priority over Proactinomyces (Jensen) Bradley & Bond, Jensenia Bisset & Moore and Gordona Tsukamura. In addition to the type species, Rhodococcus rhodochrous, nine species are recognized: R. bronchialis, R. coprophilus, R. corallinus, R. erythropolis, R. equi, R. rhodnii, R. rubrus, R. rubropertinctus and R. terrae.


Evidence for a cytosol counterpart of the major plasma membrane protein in Acanthamoeba castellanii.

Isolated plasma membranes from Acanthamoeba castellanii incorporated radio-activity when incubated in a corresponding labelled cytosol fraction. The incorporation increased linearly with time and reached saturation at high cytosol: membrane protein ratios in the incubation mixture. Polyacrylamide gel electrophoresis of treated membranes showed that the major protein, which comprised 40 to 50% of the total, was labelled, suggesting that it had exchanged with a radioactive cytosol counterpart. The same protein was discernible in polypeptide profiles of labelled cytosol and showed a higher specific radioactie membrane by solutions of high ionic strength or chelation, this protein appears to be integral rather than peripheral.


The characteristics of extracellular protein secretion by Staphylococcus aureus (Wood 46) and their relationship to the regulation of alpha-toxin formation.

The progress of secretion of alpha-toxin and total extracellular protein by Staphylococcus aureus (Wood 46), grown aerobically at 37 degrees C, in a 3% (s/v) tryptone soya broth medium supplemented with vitamins was followed. Exoprotein was secreted at a high rate by intact bacteria during the exponential phase (to 9 h) and into the post-exponential phase. After 18 h, when exoprotein accounted for 33% of the total protein in the culture, no further exoprotein was secreted although the bacterial density continued to increase at a low rate beyond this time. During the phase of active secretion, alpha-toxin represented a constant proportion of total exoprotein, the differential rate of synthesis of which increased by a factor of four after the end of exponential growth. Concomitant with the increase in the differential rate of exoprotein formation there was a fourfold increase in the intracellular concentration of RNA precursor material.


Isolation of mitochondria and mitochondrial RNA from Crithidia fasciculata.

Two methods were used to isolate mitochondria from Crithidia fasciculata. In the first method, cells were weakened by exposure to hypotonic conditions and then disrupted by blending; mitochondria were subsequently isolated using disodium 3,5-diacetoamido-2,4,6-triiodobenzoate gradients. In the second, cells were treated with digitonin before disruption; mitochondria were purified by differential centrifugation. Both preparations were examined with the electron microscope and were also shown to possess several characteristic biochemical properties of mitochondria. Kinetoplast DNA was present in the mitochondria, uncontaminated by nuclear DNA. Analysis by polyacrylamide gel electrophoresis showed two RNA components of molecular weights of 0-47 X 10(6) and 0-22 X 10(6), in addition to cytoplasmic RNA contamination. Four mitochondrial components with sedimentation coefficients of 14-6S, 11-4S, 10-1S and 9-9S were identified on sucrose density gradients. Ethidium bromide abolished the incorporation of [5-3H]uridine into the presumed mitochondrial RNA.


Host modification and restriction with a mycobacteriophage isolated from a pseudolysogenic Mycobacterium chelonei.

A pseudolysogenic Mycobacterium chelonei and its phage phi630 are described. Phage phi630 is the first mycobacteriophate reported to be resistant to the nonpolar solvents chloroform, dioxan and diethyl ether. The phage had a latent period of 75 min, a rise period of 90 min and a burst size of 5I. Evidence is presented for host modification and restriction. Phage phi630A, grown on host strain M. chelonei F-630 Rg, plated on the alternative host M. smegmatis ATCC607 with an efficiency of plating (e.o.p.) of 10(-5). Phage phi630B, grown on host M. smegmatis, plated with an e.o.p. of 10(-5) on the alternative host F-630 Rg. Phages phi630A and phi630B absorbed equally well on their alternative hosts and on their indicator host strains. The progeny of plaques from initial platings on the alternative host, when grown in the alternative host, exhibited a marked reduction in e.o.p. on their original host.


Serological grouping of virulent and avirulent strains of the lobster pathogen Aerococcus viridans.

Virulent strains of Aerococcus viridans (formerly Gaffkya homari) are the aetiologic agents of gaffkemia, a septicaemic disease of the American lobster (Homarus americanus). The virulent and avirulent forms of this bacterium, previously thought to be taxonomically indistinguishable, have been differentiated by serological studies. Antisera were produced in rabbits using autoclaved bacteria as antigens. Reactions were measured by agglutination tests using microtitre techniques and an antigenic scheme was determined. Specific antisera were prepared by absorption and used to determine antigens of strains of A. viridans and other Gram-positive cocci. In general, only virulent strains of A. viridans have antigen b. Both virulent and avirulent strains possess other antigens also detected in strains of the genus Staphylococcus.


Ultrastructure of bacteriophage phi 6: arrangement of the double-stranded RNA and envelope.

Pseudomonas phaseolicola cells synchronously infected with phi 6 were fixed and embedded by several procedures. The diameter of phi 6 measured 75 nm and its nucleocapsid 60 nm. Virus nucleocapsids were icosahedral and surrounded by a double membrane. In planar sections the nucleic acid appeared as a hexagonal ring and in cross section as two angular structures.


Bacteriophages of Streptococcus equi.

Bacteriophages were isolated from twelve lysogenic strains of Streptococcus equi. Based on sensitivity data and antiserum neutralization tests, the phage isolates were divided into two distinct but related groups. All twelve phage change the colonial morphology of S. equi from mucoid to matt. Possible phage-mediated effects on S. equi virulence are discussed.


[Genetic counselling (results of ten years experience). II. Requests (author's transl)].

The authors give a summing up of ten years of genetic counselling concerning 1271 requests and single out two equally important categories of consultants. The first might require premarital counselling (in cases of consanguineous unions, or when one of the partners or relatives are affected) but, in fact, come to consultation, four times out of ten, after marriage and even after procreation. The consultants of the second group need prenatal counselling either because a child suffers from a hereditary disorder, or because earlier pregnancies did not come to term. Whichever the type, one consultation out of seven concerned a pregnant woman. A classification by type disorder and by mode of transmission is given.


Sternum length and intermammillary distance in normal newborns.

Short sternum and widely spaced nipples are recognized clinical findings in Edwards' and Patau's syndromes and in Noonan's, Turner's and renal hypoplasia syndromes, respectively. Sternum length, intermammillary distance, length of trunk and thoracic circumference were measured in 307 consecutive live newborns. Intermammillary distance was found to have the highest partial regression coefficient over sternum length. It seems therefore advisable to consider both parameters in the phenotypic description of syndromes where an abnormal variation of one of them is suspected.


Brief communication. Transvestism in history.

Cross-dressing recorded in Western history, from mythological to modern times, is briefly reported. These accounts are presented to broaden the context of current reports of transsexualism as well as homosexuality.


Single case study. Behavioral treatment of boy with 47,XYY karyotype.

Controversy exists with regard to the genetic programmability of antisocial, aggressive behavior in males with 47,XYY karyotype. This study reports the reduction of disruptive behavior in a 7-year-old boy with this chromosomal anomaly. Behavioral manipulations of environmental contingencies were used to alter several types of problematic behaviors successfully. Theoretical and clinical implications with regard to the notion of genetic causality are discussed.


Single case study. Conjugal suicide pact.

Prior to entering into a suicide pact the married couple in this case study formed an intensely interdependent and socially isolated unit that illness threatened to dissolve. The depressed husband conveyed suicidal ideation to his wife in a manner suggestive of folie à deux.


The demonstration of a change in responsiveness of mice to physostigmine and atropine after withdrawal from long-term haloperidol pretreatment.

Mice, administered haloperidol 3 mg/kg/day, in their drinking water for 21 days, were tested for their responsiveness to cholinergic and anticholinergic drugs 4 days after withdrawal from haloperidol (or vehicle). Haloperidol-treated animals administered methylhyoscine (1 mg/kg i.p.) and various doses of physostigmine (5 to 1215 microgram/kg) displayed significantly less depression of locomotor activity than vehicle-treated animals. Atropine, 5 mg/kg, whilst ineffective in producing locomotor stimulation in vehicle-treated animals, produced marked stimulation in haloperidol-treated animals. Methylatropine (5 mg/kg) did not produce significant stimulation in either group. Dopamine receptor supersensitivity was present in these animals as haloperidol-treated mice, pretreated with alpha-methyltyrosine and reserpine, displayed a significantly greater locomotor response to apomorphine than did vehicle-treated animals. The data support the hypothesis that long-term administration of haloperidol produces an apparent hyposensitivity of central muscarinic receptors.


Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine.

Administration of 0.025--0.1 mg/kg of apomorphine i.p. to mice produced a dose-dependent locomotor depression. Haloperidol, 0.025 mg/kg, produced locomotor stimulation, whereas 0.1 mg/kg caused locomotor depression. Pretreatment with haloperidol also reversed the depression caused by apomorphine. The functional antagonism is discussed in terms of a possible agonist-antagonist interaction on dopaminergic autoreceptors.


Effect of nomifensine on central 5-hydroxytryptamine neurons.

Effects of nomifensine (8-amino-1, 2, 3, 4-tetrahydro-2-methyl-4-phenyl-isoquinoline) (NF), an antidepressant drug which inhibits dopamine uptake, on central serotonergic structures were studied in rats. NF affects of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid levels in the whole brain as well as in the separate rat brain structures. The 5-HT turnover is decreased in the whole brain and the striatum but increased in the midbrain and the hippocamp as judged from experiments with tryptophan hydroxylase inhibitor, alpha-propyldopacetamide. Pretreatment with dopamine-receptor blocking agent, spiperone, antagonized the increase of 5-HT turnover rate in brain regions mentioned above. NF stimulates the hind limb flexor reflex in spinal rat, a preparation regarded as a model for evaluation of drug action on central 5-HT neurons. This stimulatory effect was antogonized by cyproheptadine, by reserpine and imipramine. The obtained results indicate that NF activates central 5-HT neurons both directly and indirectly, via stimulation of dopamine receptors as described previously for other dopamine agonists.


Separation of pineal extracts by gelfiltration. VI. Isolation and identification from sheep pineals of biopterin; comparison of the isolated compound with some synthetic pteridines and the biological activity in in vitro and in vivo bioassays.

Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. Two low molecular weight Sephadex G-25 fractions, F2 and F3, were ultrafiltrated through the Amicon membrane UM-2. The UM-2 filtrate was subsequently filtrated through the ultramembrane UM-05 and the UM-05 filtrate was separated on Sephadex G-10 columns. After paper electrophoresis, preparative paper chromatography was carried out. The fluorescent band showing a Rf value identical with synthetic 6-biopterin was eluted; gas liquid chromatography and mass spectrometry of the isolated compound were carried out. The mass spectra of the isolated compound were shown to be identical with synthetic 6-biopterin. The results of the Crithidia fasciculata test and thinlayer chromatography study revealed that the isolated compound is identical with 6-L-erythro-biopterin. The activities of the isolated compound and of synthetic biopterin in in vitro and in vivo bioassays are demonstrated.


Serum growth hormone levels in schizophrenic patients during sleep.

Ten schizophrenic and five epileptic patients under antipsychotic drug treatment were studied to evaluate sleep-related GH secretion. Four of the schizophrenic patients had a high secretion peak of GH (range 15.2 to 38.0 ng/ml), four had a moderate peak (range 5.8--8.3 ng/ml), while two had no increase in GH secretion during sleep (range 0.5--1.0 ng/mg). Four of the five epileptic patients had a moderately increased secretion (range 5.8--9.2 ng/ml) and one had no increase in GH secretion during sleep. Thus, the GH secretory pattern varied with the patient as in known to be also with healthy individuals. However, no clear disturbances were noted in sleep-related GH secretion in schizophrenic patients receiving antipsychotic drug treatment, when compared e.g. to non-schizophrenic, epileptic patients under a same kind of drug treatment.


Regional distribution of acid phosphatase-positive axonal systems in the rat spinal cord and medulla, representing central terminals of cutaneous and visceral nociceptive neurons.

In addition to the substantia gelatinosa Rolandi, acid phosphatase active axonal systems are described (1) in the viscerosensory nucleus of the vagus nerve, (2) in Lissauer's band, (3) in the fasciculus cornus posterioris (Cajal), and (4) in the nucleus basilaris externus (Cajal). Electron microscopically, acid phosphatase is located in between synaptic vesicles of axon terminals; the vesicle population of such terminals in the Rolando substance, however, markedly differs from that in systems 1--4, characterized by the presence of large dense-core vesicles. While acid phosphatase-active axon terminals in the Rolando substance appear to subserve cutaneous nociception, circumstantial evidence suggests participation of systems 1--4 in processing visceral nociception.