Absorption of beta-methyl-digoxin determined after a single dose and under steady state conditions.

Single doses of beta-methyl-digoxin 0.4 mg were given to groups of 17-18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum or Lanitop tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of beta-methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with beta-methyl-digoxin steady state glycoside concentration were compared in a cross-over study of intravenous maintenance therapy with Lanitop ampoules or oral treatment with Lanitop tablets. For a standard daily dose of 0.2 mg beta-methyl-digoxin the serum concentrations were 1.35 +/- 0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.


Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses.

A gas chromatographic method has been employed to determine chlorthalidone in plasma and whole blood after therapeutic doses. Radioactively labelled chlorthalidone was used for in vitro studies of the uptake of chlorthalidone from plasma by red blood cells. Chlorthalidone was markedly concentrated in red cells and as a compartment they would account for at least 30% of total drug in the body after multiple doses. The ratio between the plasma and red cell concentration of chlorathidone varied between individuals. After a single oral dose of 50 mg in 6 healthy volunteers chlorthalidone was eliminated with a half-life of 51 to 89 hours. The apparent volume of distribution varied between 3 and 13 1/kg and the clearance between 53 and 145 ml/min. The mean steady-state plasma concentrations during treatment with a standard dose of 50 mg daily (n = 10) varied 5-fold between individuals. During the steady state approximately 50% of the daily dose was excreted unchanged in the urine during 24 hrs. The plasma levels observed in patients were higher than those preducted from the single oral dose studies in healthy volunteers.


Comparison of the half-life of antipyrine in plasma, whole blood and saliva of man.

A previously described GLC method has been modified and applied to measurement of antipyrine levels in plasma, blood and saliva of man following administration of a single oral dose (10 mg/kg). Tery time studied. The half-life of antipyrine determined in blood, plasma or saliva in any given individual was similar. The intersubject variation in half-life was about two-fold (n = 5). Antipyrine levels in saliva were not affected by the rate of saliva flow when collections were made continuously for 20 minutes. This study has demonstrated that kinetic data about antipyrine comparable to that from plasma may also be obtained from readily accessible tissue fluids, such as saliva  and capillary blood.


Membrane Ig on MPC11 myeloma cells: correlation between the expression of membrane Ig, a receptor for Ig and the process of secretion.

The expression of membrane immunoglobulin (mIg) was examined in three cloned MPC11-derived mouse myeloma cell lines. Membrane immunofluorescence studies demonstrated that IgG2b producer cells (P1) had complete IgG molecules, L-chain producer (L1) had only L-chain determinants and nonproducer (NP2) did not have any Ig determinants on the cell surface. An Ig receptor, with characteristics different from B lymphocyte Fc receptor, has been found to be present on secreting cells (P1 or L1), but not on the NP2 cell variant. The data reported in the present paper indicate that the expression of mIg and of the Ig receptor molecule is clearly correlated with the process of secretion. In the light of previous data reported on Ig secretion, a model is proposed which correlates the process of secretion with the expression not only of mIg, but also of the receptor for Ig.


Immunological enhancement of a murine tumor allograft by passive alloantibody IgG and F(ab')2.

The F(ab')2 fraction of an anti-tumor IgG alloantiserum induced passive enhancement of tumor allografts in inbred mice about as well as did intact IgG; i.e. apparently the Fc fragment is not required for suppressing cellular immunity. Passive F(ab')2, however, was somewhat less efficient than intact IgG or whole alloantiserum in depressing the allohemagglutinin response. The latter finding is in accord with previous observations on the relative inefficiency of F(ab')2 in feedback inhibition of the humoral response of mice to a heteroantigen.


Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis.

Selective breeding for the character "agglutinin production to heterologous erythrocytes" was performed on random-bred populations of albino mice. Two types of selection were carried out: Selection I: the first 6 generations were immunized with sheep erythrocytes (SE), then SE and pigeon erythrocytes (PE) were alternated at each generation to avoid the interference of maternal antibody. Selection II: all generations were immunized with SE 60-70 days after weaning in order to eliminate the maternal antibody. Both were selected for the character agglutinin titer 14 days after immunization using an optimal dose of erythrocytes. Selection I. The mean response to SE of the foundation population was 7.36 +/- 1.60. The selection limit was attained between the 15th and the 20th generation. The F20--F30 were considered as homozygous for the character investigated. The mean SE agglutinin titers were 9.15 (1/2820) in the high responder line and 2 (1/20) in the low responder line. This corresponds to 140-fold interline difference in agglutinin titers. SE agglutinins determined in F1 hybrids, F2 hybrids and backcrosses obtained from F23--F29 demonstrated incomplete dominance of high responsiveness (23-29%). The inbreeding coefficient produced by close colony breeding was 0.55 in high and 0.71 in low responders at the 20th generation when both lines were homozygous with respect to agglutinin synthesis. Selection II. The mean response of the foundation population to SE was 7.79 +/- 1.56. The selection limit was attained in F14--F17 generations that were considered homozygous for the character investigated. The mean SE agglutinin titer was 9.2 (1/2900) in high responders and 2.8 (1/35) in low responders, which is an 83-fold interline difference in agglutinin titers. The results of both selections indicate that the character agglutinin synthesis is subject to polygenic regulation. The heritability (h2) of this character was estimated to be between 0.18 and 0.36 (range between the extreme values of Selections I and II.


Relationship between the enhanced expression of histocompatibility antigens on interferon-treated L 1210 cells and their position in the cell cycle.

We have determined the cell cycle position of individual mouse leukemia L 1210 cells by cytophotometric and autoradiographic techniques and simultaneously determined the amount of histocompatibility antigens expressed on the surface of individual cells by quantitative immunofluorescence. Interferon treatment of L 1210 cells was accompanied by an enhanced expression of histocompatibility surface antigens. The distribution of interferon-treated cells in the various phases of the cell cycle was similar to that for control cells and the enhanced expression of histocompatibility antigens was observed on interferon-treated cells in all phases of the cell cycle. We conclude, therefore, that this enhancement is not due to a preferential concentration of these cells in any one particular phase of the cell cycle.


Reversible binding of a T cell factor on IgG-coated sepharose beads.

Supernatants of alloantigen-activated T cells contain a number of factors, including an immunoglobulin-binding factor (IBF) which inhibits complement-induced hemolysis of sheep erythrocytes coated with anti-Forssman IgG antibodies and a factor which suppresses IgM antibody synthesis in vitro. These two factors may be identical, since they are simultaneously retained on Sepharose beads to which IgG has been coupled and can be recovered by elution at pH 2.8. They do not bind to Sepharose beads to which IgM of F(ab')2 fragment of IgG has been coupled, demonstrating that they have a selective affinity for the Fc region of IgG. In addition, the fixation of IBF on the Fc portion of IgG reversibly inhibits subsequent binding of the first component of complement (C1), thus indicating that IBF does not irreversibly alter the C1 binding site(s) of IgG.


Synthesis of eel-calcitonin and (asu1,7)-eel-calcitonin: contribution of the disulfide bond to the hormonal activity.

Eel-calcitonin and its [asu1,7]-analog, deamino-dicarba-analog, were synthesized by the conventional solution method. The natural-type product showed 4300 MRC U/mg in the hypocalcemic potency which was comparable to that of the natural hormone isolated from eel. Hormonal activity of the Asu-analog was also as high as 3400 MRC U/mg.


Phosphorus-containing heterocycles as fungicides: synthesis of 2,2'-diphenylene chlorophosphonate and 2,2'-diphenylene chlorothiophosphonate.

Synthesis of 2,2'-diphenylene chlorophosphonate and 2,2'-diphenylene chlorothiophosphonate is described through the interaction of 2,2'-dihydroxybiphenyl with phosphoryl chloride and thiophosphoryl chloride respectively. These compounds were screened for their fungicidal activity.


On the metabolism of prostaglandins by rat brain homogenate.

Using radio-immuno assays for prostaglandins and prostaglandin metabolites, three prostaglandin metabolizing enzymes were found in the 100,000 X g supernatant of rat brain, 15-hydroxy-prostaglandin-dehydrogenase, delta13-reductase and prostaglandin E-9-keto-reductase. Specific activity of the latter enzyme was highest in striatum and midbrain and lowest in cortex, cerebellum and spinal cord.


Changes in blood tryptophan level during sleep deprivation.

Prolonged sleep deprivation elicits a significant elevation of the plasma level of free tryptophan which appears to be involved in increased excretion of 5-HIAA during this state through enhanced 5-HT synthesis.


Purification and partial characterization of lysozyme from mouse small intestine.

Lysozyme was isolated from the small intestine of mice by combined ion-exchange and molecular sieve chromatography. This lysozyme differs from that isolated from the urine of mice with monocytoma in amino acid composition, and migration rate in cellulose acetate electrophoresis. As intestinal lysozyme originates at least in part from the Paneth cell, our results point towards the existence of isozymes of lysozymes in mice.


Galactose transfer and UDP-galactose hydrolysis in urine from normal Balb/c and Balb/c YC8 mice.

By chromatographic method we have shown the existence of a complex system for galactose transfer from UDP-galactose and for nucleotide hydrolysis in urines from Balb/c YC8 and normal Balb/c mice. By action of sera from normal and ascitic mice as source of enzyme, we have been able to detect transfer for galactose in urines from ascitic mice and an important inhibitory effect of the nucleotide sugar hydrolysis by the sera with urines from normal mice.


Monoamine oxidase activity in rat erythrocytes: evidence for its localization in reticulocyte mitrochondria.

During growth of young rats, monoamine oxidase activity in erythrocyte membrane preparations decreases more rapidly than reticulocyte concentrations in the respective blood samples. Since reticulocytes lose their mitochondria prior to the substantia reticulo-filamentosa, the non-linear correlation between monoamine oxidase activity and reticulocyte counts indicates that erythrocyte monoamine oxidase is located in reticulocyte mitochondria.


The oxidative metabolism of alpha-chlorohydrin and the chemical induction of spermatocoeles.

alpha-Chlorohydrin (I) is oxidatively metabolized to beta-chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of alpha-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.


Developmental characteristics of histamine methyltransferase and phenylethanolamine-N-methyl-transferase of rat brain.

The specific activity of histamine methyltransferase of rat brain increases rapidly from the 16th until the 25th day of gestation (7 days after birth). The specific activity of phenylethanolamine-N-methyl-transferase shows a rapid increase during the 1st and the 2nd week after birth, the adult values being obtained by the end of the 2nd week.


Alteration of cholesterol synthesis in rat liver as induced by 4-methyl-5-hydroxy valeric acid.

The rate of cholesterogenesis in rat liver, measured by the incorporation of labelled acetate or mevalonate into cholesterol, was significantly supressed by the use of 4-methyl-5-hydroxy valeric acid sodium salt. This effect cannot be explained by changes in HMG CoA reductase activity.


Location of an eye mutant in the onion fly Hylemya antiqua Meigen using a pericentric chromosome inversion.

With the use of a pericentric inversion in chromosome 3, an eye color mutant in the onion fly was located in chromosome 3. No recombination occurs in males; 40.2% recombination was observed in females. This linkage through the male facilitates further cytogenetic research on structural aberrations involving chromosome 3.


The phylogenetic status of phyllomedusine frogs (Hylidae) as evidenced from immunological studies of their serum albumins.

Based on immunological comparisons of the serum albumins of phyllomedusine frogs with both hyline and bufonid species, it is suggested that phyllomedusine frogs be erected to familial status within the superfamily Bufonoidea.


Insulin resistance and related electrical activity of the small intestine.

Postprandial disruption of the migrating myoelectric complex is of longer duration in obese hyperinsulemic Zucker rats than in control rats. No postprandial disruption was seen in an insulin resistant dog. This gives further support to a major role for insulin in control of gut activity.


Ultradian and other rhythms in human respiration rate.

Twelve male subjects had their respiration rate (RR) measured at 3 min intervals for 6 h. Although there were substantial individual differences, most subjects demonstrated a 90 +/- 15 min rhythm of RR, with several subjects also showing 60 +/- 10 min and 30 +/- 3 min rhythms.


Coordinated activation of muscle fibres by different conduction velocities in branches of a crustacean motor axon.

Higher conduction velocities in branches of the fast excitor axon to distal muscle fibres ensure that these fibres are activated almost simultaneously with proximal fibres in the claw closer muscle of lobsters, producing a contraction of maximal force.


Effect of sulfated and non-sulfated gastrin and octapeptide-cholecystokinin on cat gall bladder in vitro.

This study demonstrates that for the isolated cat gall bladder a smaller molar dose of the sulfated form of OP-CCK and gastrin is required to produce contraction as compared to the respective non-sulfated forms. For OP the D50 for the sulfated form versus the non-sulfated form was 1.94. For gastrin it was 1.10.


Resistance of cold-exposed rats to aflatoxin.

Male rats kept at a temperature of 4 degrees-5 degrees C were refractory to a lethal dose of aflatoxin compared to animals at 20 degrees-21 degrees C which exhibited a high mortality and marked liver damage. It is suggested that this decreased susceptibility is mediated through a stimulated microsomal drug-metabolizing system in cold environment.


Enhancement of tubular organic base accumulation in renal cortical slices by repeated administrations of Tris-hydroxymethyl aminomethane, tromethamol (THAM) to rats of different ages.

After repeated THAM administrations to rats of different ages, an enhancement of THAM accumulation in renal cortical slices was observed, except in newborns. This effect can be interpreted as a specific substrate stimulation of the organic base transport system.


RNA synthesis in alpha-amanitin-poisoned rats: prevention of recovery by inhibition of protein synthesis.

The treatment with cycloheximide of rats previously poisoned with alpha-amanitin hinders the recovery of RNA synthesis observed in the liver of rats treated with alpha-amanitin alone. The recovery of RNA synthesis can be ascribed to the capability of poisoned rats to synthesize new RNA-polymerase II.


Hypertension mediated by the activation of the rat brain 5-hydroxytryptamine receptor sites.

5-Hydroxytryptamine (5-HT) administered intraventricularly (i.vent.) in rats produced hypertension without considerable changes in heart rate. After transsection of the spinal cord or i.vent. administration of methysergide, 5-HT failed to produce the pressor effect. Thus, the hypertension results from the activation of 5-HT receptor sites of the rat brain.


An electron microscopic study on the autonomic innervation of the rabbit parotid gland.

As visualized in the electron microscope, the parotid gland of the rabbit has a dual innervation. Both adrenergic and cholinergic nerves are equally distributed in the parenchyma and often run together within the same nerve bundle. Nerve terminals are observed not only subjacent to the basement membrane but interposed between the latter and the acinar cells, where they establish a close membrane to membrane contact with the latter.


The fine structure of Walker 256 carcinoma cells.

Several ultrastructural features of Walker 256 rat tumor cells which have not been observed before are revealed. Nuclear bodies either singlely or in pairs were found in some cells. Cytofilaments were observed in the cytoplasm and cytoplasmic projections in a few cells. Desmosomes which are usually regarded as a feature of differentiated cells were also observed.


Pregnancy following segmental isthmic reversal of the rabbit oviduct.

Microsurgical reversal of a segment of rabbit proximal tubal isthmus has been followed by normal pregnency in the first two animals to undergo the procedure. Establishment of pregnancy despite radical modification of the oviduct furnishes the opportunity to gain new insights into the mechanisms controlling tubal ovum transport and emphasizes the evolving feasibility and importance of tuboplastic microsurgery both as a research tool and clinical procedure.


Tumor promoting constituent of Euphorbia serrata L. latex.

Euphorbia serrata latex has initially ingenol-3-palmitate, which by action of silica gel is converted to ingenol-20-palmitate. The former is responsible for the irritant and cocarcinogenic activity of the latex on mouse ear and on mice back skin.


Pregnancy specific beta1-glycoprotein--a product of the syncytiotrophoblast.

Pregnancy specific beta1-glycoprotein (PSbetaG) has been identified in vitro in trophoblast cultures and in vivo, using transmission electron microscopy, in the syncytiotrophoblast, PSbetaG may, like other pregnancy proteins, have immunosuppressive properties.


Effect of an antiandrogen on the lymphoid system.

A side-effect of the administration of cyproterone acetate, an antiandrogenic steroid, to newborn, juvenile or adult male mice (in doses comparable to those used clinically) was found in a marked reduction of the white pulp of the spleen and reduced weight or even absence of the thymus.


Progesterone formation and metabolism by rabbit placenta in vitro.

4-14C-Progesterone and 4-14C-pregnenolone are metabolized in vitro by rabbit placenta, at day 15 and 28 of gestation, exclusively to compounds reduced in ring A (5beta) and at carbon 3 and 20.


The underwater electro-olfactogram: a tool for the study of the sense of smell of marine fishes.

Recording the olfactory receptor activity of marine fishes presents problems due to the shunting of the electrical signals by the highly conductive sea water, which results in significant signal loss. By recording the large signal-to-noise ratio D. C. potentials using the underwater electro-olfactogram (EOG), we were able to study olfactory receptor properties of freshwater and marine fishes in a comparable manner.


The pituitary-gonadal axis in spinal cord injury.

Our study documented that serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol in 14 of 15 males with spinal cord injury (SCI) were within the normal range of those of age-matched controls. One patient had gynecomastia with compensated gonadal insufficiency of undetermined etiology. Five males with SCI showed a normal rise in serum testosterone levels following stimulation with human chorionic gonadotropin. Testicular biopsy in one of two males with SCI showed spermatogenic arrest. One of the biopsies showed immunoglobulin G immunofluorescence around the seminiferous tubule; the other demonstrated immunoglobulin A immunofluorescence in the spermatogonia. These findings suggest that, if a high incidence of impaired spermatogenesis does occur in spinal cord-injured patients, it is unlikely to be secondary to hormonal imbalance.


Sexual function after major resections of the sacrum with bilateral or unilateral sacrifice of sacral nerves.

The sexual function of nine patients with severance of sacral nerves bilaterally (five patients) or unilaterally (four patients), performed during operations for radical extirpation of tumors of the sacrum or its vicinity, was studied. Sexual histories were obtained and sensibility tests were performed. In four of the five male patients an attempt was made to collect electromyographic recordings from the external urethral and anal sphincters during ejaculation. Bilateral loss of S3 to S5 nerves in two women seemed not to affect their sexual function. Bilateral loss of S2 to S5 nerves in one man was compatible with gratifying sexual intercourse, the stimulation for erection being purely psychogenic, and "ejaculation" of a dripping nature. Unilateral loss of all sacral nerves did not impair previously normal sexual function, although the penises and vulvae of these patients were anesthetic on one side. The sensibility of the penis seemed to be subserved by the second sacral nerve. The myoelectric activity of the striated urethral and anal sphincters during ejaculation recorded in one patient with unilateral total loss of sacral nerves was normal bilaterally considering the duration of, and intervals between, the clonic contractions.


Prolactin after gonadotropin-induced pregnancy.

Prolactin levels during a gonadotropin-induced pregnancy have not been previously reported. A patient with Forbes-Albright syndrome is described. She received radiation therapy, with cessation of her galactorrhea, but she remained amenorrheic. Three years after irradiation, a pregnancy was successful induced with human menopausal gonadotropins and human chorionic gonadotropin. Prolactin levels determined prior to gonadotropin therapy, during an insulin hypoglycemia stimulation test, serially during pregnancy, and postpartum during lactation are presented. These levels are compared with the previously reported levels for basal prolactin, response to insulin hypoglycemia, pregnancy, and lactation. Possible etiologies for the abnormal values and responses obtained from investigation of this patient are discussed.


Plasma prostaglandin F 2-alpha levels in dysmenorrehic women.

Plasma prostaglandin F 2-alpha (PGF 2-alpha) concentrations were compared in nine ovulatory dysmenorrheic women, one dysmenorrheic oral contraceptive user, and two nondysmenorrheic control subjects, in an effort to demonstrate a relationship between plasma PGF 2-alpha levels and dysmenorrhea. In addition, the effects of aspirin, a known inhibitorof prostaglandins synthesis, on dysmenorrhea and on PGF 2-alpha levels were investigated. No statistical difference was demonstrated between the plasma PGF 2-alpha levels of dysmenorrheic and nondysmenorrheic subjects throughout the menstrual cycle. Attainment of an adequate salicylate level was accompanied by a significant decrease in PGF 2-alpha levels. All dysmenorrheic subjects reported improvement in symptoms while taking aspirin. The greatest subjective relief was reported by women who began taking aspirin (10 grains every 4 hours) 3 or more days prior to the onset of bleeding.


Antispermatozoal effects of human seminal plasma--an immunologic phenomenon.

Semen samples were obtained from seven men who had self-agglutination of spermatozoa, and a spermatozoal antibody in the immunoglobulin G (IgG) fraction of their blood. The seminal plasma of these men produced spermatozoal immobilization and agglutination when added to normal semen from healthy men. Analysis of the seminal plasma samples showed that they contained IgA and complements C-3 and C-4, whereas only 1 of 10 samples from normal men contained IgA, and none had complements C-3 and C-4. The IgG levels of the seminal plasma from the study group were higher than those of the controls. It is suggested that the mechanism of spermagglutination is one of autooimmunization in which the main antibody is IgA from the genital tract, augmented by a circulating antibody from the IgG fraction of the blood.


Clinical experience with sperm antibody testing.

Of the 724 patients examined for circulating spermagglutinating antibodies by the Kibrick spermagglutination test, 95 (13.1%) were found to be positive. Almost 20% of the 406 male patients demonstrated autoantibodies. This high incidence may be explained by the selected population studied. Of 50 males tested who demonstrated more than 10% agglutination in their semen, but otherwise were normospermic, 42% demonstrated autoantibodies. Of the 318 females examined, 14 (4.4%) demonstrated sperm-agglutinating antibodies. Of the 315 male and female patients examined for circulating sperm-immobilizing antibodies by the Isojima sperm-immobilization test, 14 (4.5%) were found to have antibodies. Of the 162 males treated, 10 (6%) were positive for antibodies by this technique, as were 4 (3%) of the 153 women tested.


Wound healing: a model for the study of diabetic angiopathy.

Wound healing as a model for diabetic angiopathy has been studied by light and electron microscopy. Biochemical studies of the rate of incorporation of 3H-proline and 3H-thymidine into collagen and DNA, respectively, have confirmed the morphologic observations. In both the normal and the diabetic, there was a marked decrease in the rate of collagen and DNA synthesis, suggesting that most of the cells in the biopsies were stunned by the injury and ceased DNA replication during the initial phase. In control mice this decrease was followed by a modest but significant burst of DNA replication, which peaked at two hours and by the fourth hour had returned to the one-hour level. In the diabetic this burst of DNA replication was absent and no capillary morphogenesis was seen at two, four, and eight hours. At 16 hours, there were only a few abnormal nascent vessels observed in the diabetic and antiserum-treated mice. The peak in the rate of collagen synthesis at four hours correlated well with the condensation of collagen at the wound margin and the fibroblast rough-endoplasmic-reticulum (RER) proliferation. In the diabetic mice, there was a significantly attenuated rate of collagen synthesis for the entire 16-hour period. The lack of DNA replication, capillary morphogenesis, fibroblast RER proliferation, and decreased collagen synthesis in the diabetic mouse can be considered interrelated and significant factors in the diabetic's impaired response to cellular injury. In view of the increased frequency and severity of injury to the circulation of the diabetic and the impaired response to repair such injury, it is likely that wound healing is a promising model for diabetic angiopathy.


The problems of retinal blood flow in diabetes.

Three methods are available for measurement of retinal blood flow: cinefluroescein angiography, measurement of mean transit time, and estimation of volume flow by laser-Dopler velocimetry. Cineangiography requires intra-arterial injection for volume flow measurement, and this greatly inhibits its use. Difficulties also arise in estimating the relation of the axial to the mean flow, since it is now known that the retinal flow is plug flow. Transit time measurement using fluroescein has recently been automated and thus allows for more accurate measurement and better estimation of volume flow. The problems of estimating vascular volume and allowing for leakage have not been overcome. Laser-Doppler velocimetry measures mean red cell velocity but its relation to volume flow has not been established. Using the mean-transit-time method, several authors have found reduced transit time and increased volume flow in patients with mild and no retinopathy, compared to normals and those with more severe lesions, This most probably is due to autoregulatory adaptation and, possibly, to hypoxia. In more severe retinopathy, flow is reduced and there are large areas of nonperfusion. These areas are the result of abnormality of the endothelial cells and also of the blood within the vessels, which probably coagulates more easily than in normals. These areas are of importance because they stimulate the growth of new vessels.


Plasma protein changes, blood viscosity, and diabetic microangiopathy.

Diabetic microangiopathy is a slowly progressive condition that usually manifests itself years after the onset of the carbohydrate-metabolism disturbance. It is a far more striking problem in some diabetics than in others. Differences in the pattern of its effect in several body systems suggest that the local vascular disturbance is a mixture of a general microcirculatory change in diabetes and a specific vascular alteration in each tissue. Its manifestations in the individual diabetic appear to be influenced by both elements. Evidence is presented that plasma protein changes in diabetes and their effects on blood flow play a role in acclerating the rate of progression of diabetic microangiopathy by raising plasma viscosity and by increasing the affinity of erythrocytes for each other. The plasma protein change is dominated by a possibly hormonally mediated pattern of alpha-globulin elevation seen in many chronic disorders. This elevation of acute-phase proteins is not likely by itself to produce diabetic microangiopathy, but it may cause an additional stress on the metabolically disturbed diabetic microcirculation. The basic change is a disturbance in the average molecular shape of the plasma proteins that both directly increases plasma viscosity and enhances the aggregation of erythrocytes. Studies are now in progress to determine which of these two mechanisms is more likely to be important in accelerating the development of diabetic microangiopathy.


Renal function changes in diabetes.

The present studies show that a number of functional abnormalities are present in the kidney in early diabetes, especially during poor regulation. Normalization of these functions and changes in renal and glomerular size are found during complete diabetes control. The results further support the idea that great efforts should be made to maintain the best possible control situation in diabetic patients. Our studies also indicate that antihypertensive therapy may be beneficial for young, proteinuric diabetics and may postpone the stage of renal insufficiency.


Leukocyte chemotaxis in diabetic patients and their nondiabetic first-degree relatives.

Leukocyte chemotaxis wasmeasured in 108 subjects: 20 normal controls, 36 insulin-taking diabetics (15 being index patients), and 52 nondiabetic first-degree relatives of index patients. The relatives had a mean chemotactic index (CI) significantly lower than that of the controls (individually, 25 per cent had CIs lower than the lowest of the controls); and the diabetics had a mean CI significantly lower than that of the relatives. The impairment of leukocyte chemotaxis measured in the first-degree relatives of diabetic index patients does not appear to be associated with an increased susceptibility to infection and suggests that the impaired leukotaxis is due to an inherent defect--perhaps genetic--in leukocyte function.


Red-cell aggregation and red-cell deformability in diabetes.

The anomaly of the viscosity of human blood is more pronounced in diabetics. This is caused by an increase in plasma viscosity, a more pronounced red-cell aggregation, and a reduction of individual cell deformability. The changes in viscosity and in red-cell aggregation both are the consequence of abnormal plasma proteins, the incidence of which is largely independent of the onset and duration of disease, and actual metabolic state. The presence of complicating infectious diseases further aggravates the pathologic red-cell aggregation. The decreased red-cell deformability is largely independent on onset, duration, and complications but depends critically in the incident metabolic control of the diabetics. The possible role of hemorrheologic factors in the development of microangiopathy is discussed.


Mean retinal circulation time as determined by fluorescein angiography in normal, prediabetic, and chemical-diabetic subjects.

A preliminary survey has been completed using manual densitometric technics to determine the mean retinal circulation times in groups of normal controls, offspring to two diabetic parents with normal glucose tolerance (prediabetics), and offspring of two diabetic parents with abnormal glucose tolerance (chemical diabetics). Comparisons of the mean retinal circulation time showed differences between the left eye and right eye in prediabetic and chemical diabetic groups and a sex difference in both normals and prediabetics. In addition, both age and per cent ideal body weight were inversely related to the mean retinal circulation time. The levels of fasting serum cholesterol, triglyceride, and growth hormone, in many instances, also appeared to be inversely related to the mean retinal circulation time. Similarly, the degree of glucose tolerance (determined by the area under the glucose curve above baseline) was significantly inversely related to the mean retinal circulation time. The mean retinal circulation time adjusted for per cent ideal weight was analyzed separately for both right eye and left eye, and a significantly shorter mean retinal circulation time was noted, particularly in males, for prediabetics than for normal controls and for chemical diabetics than for both prediabetics and normals. Analysis of the mean retinal circulation time adjusted for age showed similar differences. It is postulated that the genetic prediabetic state with or without glucose intolerance might be associated with significant alterations of mean retinal circulation time independent of age and per cent ideal weight. It is also suggested that a number of potentially meaningful interrelationships between the degree of glucose intolerance and/or hyperlipidemia might exist and should be further quantified.


Biochemical alterations of the human glomerular basement membrane in diabetes.

Only from the kidney glomerulus can the capillary basement membrane be isolated in quantities sufficient for biochemical analyses. In this study an attempt has been made to obtain a basement membrane as pure as possible, without contamination from cells or mesangium. In diabetic nephropathy, the glomerular basement membrane shows a decreased content of cystine, but hydroxylysine concentrations was only slightly higher than in normal material. The concentration of glucose was significantly increased. Immunofluorescent studies indicated the presence of serum proteins in the diabetic glomerular basement membrane, probably as a result of increased membrane permeability.


The relationship between diabetic capillaropathy and myocardial infarction: a hypothesis.

It is believed that diabetic patients with clinical evidence of diabetic capillaropathy have a greater risk of myocardial infarction than those with the same duration of disease but no evidence of capillaropathy. If the hypothesis presented here is correct, then early attention to diet, perhaps as a means of slowing the rate of atherosclerosis, will be as important as insulin in reducing current mortality statistics.


RP4 promotion of transfer of a large Agrobacterium plasmid which confers virulence.

Introduction of RP4 plasmid into Agrobacterium tumefaciens promotes the transfer on solid medium of large virulence-associated plasmids from virulent donor strains to a plasmidless avirulent recipient. Exconjugants were selected for the ability to utilize octopine or nopaline as the sole source of arginine, traits which are coded for by virulence-associated plasmids in the strains employed here. All exconjugants retained the arginine auxotrophy of the recipient strain, and were resistant to ampicillin and kanamycin, drugs to which RP4 confers resistance. Five exconjugant clones from one cross were shown by alkaline sucrose gradient analysis to contain both RP4 plasmid and the large virulence-associated plasmid of the donor strain. All five exconjugants exhibited virulence on carrot, sunflower and kalanchoe plants. These results indicate that virulence and the ability to degrade octopine are plasmid-borne traits in A. tumefaciens strains 15955 and A6, and extend the evidence that large plasmids in A. tumefaciens are vectors of virulence genes.


Diploid gynogenesis in the Mexican axolotl.

Gynogenetic diploid axolotls were produced by activating eggs with ultraviolet-inactivated sperm, and then subjecting the activated eggs to heat shock. Optimal conditions for ultraviolet inactivation of the sperm, and for suppression of the second meiotic division by heat shock, were established. Gynogenetic diploids produced by these procedures included progeny homozygous for recessive alleles carried by a heterozygous mother. Gynogenesis could, therefore, be used to uncover new mutations more rapidly than by conventional inbreeding techniques. However, some difficulty was encountered in recognizing mutant phenotypes because of the high incidence of abnormalities and deaths. Defective embryos probably resulted from a combination of heat-shock-induced damage to the eggs and the expression of deleterious recessive alleles carried by the mother.


Evolution of Hawaiian drosophilidae. II. Patterns and rates of chromosome evolution in an antopocerus phylogeny.

The phylogenetic relationships of seven species of the genus Antopocerus (Family Drosophilidae) have been determined by means of a study of the metaphase configurations and polytene chromosomes. Based on biogeographical, behavioral and cytogenetic information A. longiseta from Molokai is tentatively identified as the primitive species of the genus. The metaphase karyotypes of all Antopocerus species are either five pairs of rod chromosomes and a pair of dots (5R1D), or six rods (6R). Heterochromatin additions converted the dots to rods. Chromosome breakpoints for inversions also are clustered at heterochromatic loci. The chromosome segments between heterochromatic loci may represent sets of functionally related loci, evolving as a unit. The rate of chromosomal inversion substitution is estimated in the origin of the taxon (probably a subgenus of Drosophila rather than a separate genus). It averages no greater than one substitution per 1,000 years, or one per 5,000 generations. The average genetic death rate per generation of one individual per hundred is required to achieve this substitution rate. The rate of inversion substitution during radiation of this taxon may be only 4.4 X 10(-3) times as fast as that present in forming the taxon. Alternatively, radiation may have required only 250,000 years if rates of substitution are the same as in the origination of the taxon. Average rates of substitution reflect genetic accidents, selection pressures and rates of adaptation to new niches, as well as the rate of encountering new niches. Rate of adaptation probably is much greater in this instance than rate of encountering new niches. Rate of adaptation probably is much greater in this instance than rate of encountering new niches. Therefore, the average rate of evolution reflects more nearly biogeographic and ecological factors than genetic factors.


The evolutionary advantage of recombination. II. Individual selection for recombination.

Based on the FISHER-MULLER theory of the evolution of recombination, an argument can be constructed predicting that a recessive allele favoring recombination will be favored, if there are either favorable or deleterious mutants occurring at other loci. In this case there is no clear distinction between individual and group selection. Computer simulation of populations segregating for recessive or dominant recombination alleles showed selection favoring recombination, except in the case of a dominant recombination allele with deleterious background mutants. The relationship of this work to parallel investigations by WILLIAMS and by STROBECK, MAYNARD SMITH, and CHARLESWORTH is explored. All seem to rely on the same phenomenon. There seems no reason to assume that the evolution of recombination must have occurred by group selection.


Gene conversion: a hitherto overlooked parameter in population genetics.

Gene conversion causes deviations from the 2:2 segregation of allele pairs in meiosis. Thus, gene conversion is a potential cause for changes of allele frequencies in populations. Equations are derived for the effects of conversion in a large random-mating population. The influence of gene conversion on allele frequencies is compared with that of spontaneous mutation and meiotic drive.


Clines with variable migration.

The consequences of a discontinuity in the migration rate and of a geographical barrier in the habitat are studied in a diffusion model of migration and selection. The treatment is restricted to a single diallelic locus in a monoecious population in the absence of mutation and random drift. It is supposed further that migration is independent of genotype, the population density remains constant and uniform, and Hardy-Weinberg proportions obtain locally. It is shown that a discontinuity in the migration rate leads to a jump in the slope of the gene frequency, but not in the gene frequency itself, while a localized geographical barrier has precisely the opposite effect. These features of the gene frequency behavior are quantitatively related to the migration rate. The influence of the above inhomogeneities in migration on the maintenance of an allele in an environmental pocket is examined. The extent to which the critical condition for polymorphism is made less stringent by decreased migration outside the pocket and by a geographical barrier between the pocket and the rest of the habitat is evaluated.


Genetic variation in heterogeneous environments.

A model of population structure in heterogeneous environments is described and conditions sufficient for maintaining a polymorphism are derived. The absolute fitness of any genotype is regarded as a function of location in the niche space and the population density at that location. Two modes of habitat selection are examined: (1) organisms are distributed uniformly over the environment; and (2) each organism selects to occupy that habitat in which it is most fit ("optimal habitant selection"). Sufficient conditions for maintenance of genetic polymorphisms are derived for both models. In populations which do not practice habitat selection heterozygote superiority averaged over the environment is sufficient to guarantee the existence of polymorphisms. Comparable conditions for populations which practice optimal habitat selction are much less restrictive. If the heterozygotes are superior to one homozygote in any one part of the niche and to the other homozygote in any other part of the niche then a polymorphism will be defined. A positive correlation between genetic and environmental variation follows from the model with habitat selection, but not from the other. The adaptive significance of polymorphisms thus depends on how animals behave.


[Observation of a distinct humeral spur formation].

A 23 year old male with a mirror right hand, duplicated ulna and aplasia of the radius is presented. A large deformity of the distal and anterior surface of the humerus was also noted. Based on clinical documentation and X-rays it was felt that this unusual bony formation probably represented a minimal rudiment of the radius and that the bone deformity at the distal end of the humerus did not represent a supracondylar humeral spur which is occasionally seen in humerus without any concommittent congenital deformities, as is nearly always seen in mammals.


[Static and dynamic studies on finger arthrodeses].

Some general techniques in arthrodesis of finger joints are described. Then biomechanical measurements were made after compression arthrodesis with screws, crossed KIRSCHNER wires, tension band wiring, compression plates (Swiss AO), and self compression plates, creascent shaped (MITTELMEIER). By screws, a maximal compression between 25 and 34 kp is achieved. Using a selfcompressing, bent, crescent shaped plate, one gets a compression of about 18 kp. This osteosynthesis resists a high deflection momentum if edgewise inserted.


[Advances in osteosynthesis of hand fractures].

In recent years stable internal fixation of hand fractures has become more commonly used though the majority of fractures of the hand bones are still treated successfully by other orthopedic means. We feel that in selected fractures internal fixation achieves better results than conservative treatment. Operative methods with less traumatic skin incisions for the fixation of multiple metacarpal fractures are proposed. A retrograde screw fixation technique is presented which permitts application of compression in very small bone fragments, which risk to be crashed by standard screwing. Results of 60 internal fixations of carpometacarpal fractures of the first metacarpal are reported. Follow-up examination of 41 patients between 1-7 years following surgery, revealed posttraumatic arthritis only in 3 joints, although remaining small articular irregularities were frequently seen on X-ray. Secondary angulation occured in four cases in spite fixation. This was due to poor cortical fixation on the palmar side of the fracture, thus in such cases temporary plaster cast should entirely be applied.


[Stable osteosynthesis in reconstructive surgery of the hand].

Stable fixation of the skeleton of the hand hat its merits especially in reconstructive procedures, such as osteotomy for malunited fractures, bone grafting procedures for loss of bone substance, fusion of any of the numerous joints in the hand and finally for finger as well as metacarpal transfer. Stable fixation is useful also in combined procedures on bone, tendons and skin. The aim of stabilization is immediate restauration as a lever arm in the motor system of the extremity. This may be achieved using adequate metalimplants based on biomechanically sound principles as outlined above.


[Osteosyntheses in rheumatoid arthritis].

The wrist joint is fused by an original method consisting of a Rush pin from the third metacarpal bone high up in radius and secured against rotation by two staples between carpal bones and radius. The MP-joint of the thumb is arthrodesed by aid of a staple with compression - a special instrumentarium is used. PIP-joints were fused according to BOYES technique and the DIP-joints with compression screws.


[Computer sensomtery as objective examination of sensation in the finger area].

The authors described what they believe to be a more objective method for evaluation of sensation within the digital pulp. It requires the use of electronic equipment including EEG to record the evoked potentials. With further refinement this method should become a valid tool in the objective examination of sensory patterns.


[Conservative treatment of extensor tendon injuries].

Report on 35 cases of mallet finger treated conservatively: a circular plaster cast was modeled in hyperextension of the distal interphalangeal joint. The immobilisation of the whole finger form the tip to the proximal phalanx was maintained for six weeks. The reported results were good or excellent with the exception of two cases.


[Scintigraphic demonstration of the synovial membrane].

A new technique to diagnose and control the progress of pcp in the hand is described using Tc 99 m to visualize inflammatory reactions in various tissues. Objectivity, repeatability and the possibility to see the disease in its earliest stages are advantages of the method.


The effect of motor-response-deprivation on contingent negative variation (CNV). III: relation with Maudsley Personality Inventory (MPI).

The contingent negative variation (CNV) was correlated with Maudsley Personality Inventory (MPI) in 43 healthy adults as follows: (1) The conventional CNV with motor-response showed a negative correlation with the scores of extroversion in the MPI (E-scores). The recovery of the conventional CNV after verbal extinction showed both a negative correlation with the E-scores and a politive correlation with the scores of neuroticism (N-scores). (2) The motor-response-deprived CNV in the stimuli and nonresponse sessions (Sa and Na) showed no correlation with the MPI, because they fluctuated according to the subject's attentiveness. On the other hand, the CNV in the discrimination session (Da) with constant attentiveness to stimuli showed a positive correlation with the N-scores. (3) The response times in the control and response sessions showed a positive correlation with the N-scores in males and a negative correlation in females. The correlation with the E-scores was nearly opposite.


Effects of L-dopa and vitamin B6 on electroencephalograms of schizophrenic patients: a preliminary report.

1. To assess the therapeutic effect of low-dose L-Dopa therapy and associated EEG changes in chronic schizophrenia, 10 patients with a mean duration of illness of 12.4 years were treated with L-Dopa for a period of eight weeks during which the dosage was increased progressively from an initial level of 300 mg q.d. biweekly up to 600 mg q.d. The treatment was moderately effective in one case and slightly efficacious in one, produced no significant change in the conditions of seven patients while the remaining patient showed exacerbation; hence a noticeably low rate of improvement. There occurred no significant changes in the EEG pattern in the series of 10 patients on the average. The individual patients' responses, nevertheless, could be classified into three groups: one with no observable EEG changes, the second showing a slight degree of increase in alpha activity and the third exhibiting diminution of alpha activity in the EEG. The patients in the latter two groups all had durations of disease less than 10 years. 2. Observations were made primarily of changes in the EEG in 20 chronically schizophrenic patients with a mean duration of disease of 13 years receiving 60 mg of vitamin B6 (as pyridoxal-5'-phosphate) daily over a period of four weeks. Slight increase of alpha activity and decrease of theta activity in the EEG were noted on the average of the 20 cases, in response to the vitamin B6 therapy. The increase of alpha activity was frequently seen among patients with a duration of illness less than 10 years whose pretreatment EEG pattern had been alpha dominant (five out of 10 cases), whereas a slight ameliorative tendency of EEG was observed only in one out of 10 patients whose pretreatment EEG pattern had been slow-wave dominant. Symptomatic improvement was evident only in one of the 20 cases studied. 3. Observations were made of the therapeutic effect and associated EEG changes in eight patients receiving combined medication of 200 mg L-Dopa and 30 mg vitamin B6 (as pyridoxal-5'-phosphate) daily for a period of 12 weeks. Of these eight patients with a mean duration of disease of 18.3 years, two showed excellent response, three good and three fair; hence good to excellent responses attained in five out of the eight cases or 62.5%. A marked increase in alpha activity in the EEG occurred from the 2nd to 4th weeks onward in all eight cases. The EEG changes were likely to precede the symptomatic improvement. 4. To sum up the results of these three clinical trials, administration of L-Dopa alone resulted in practically no symptomatic improvement or EEG changes in patients with chronic schizophrenia whilst vitamin B6 administered singly as pyridoxal-5'-phosphate scarcely produced significant symptomatic improvement but brought about a slight ameliorative tendency in the EEG of such patients. Both symptomatic amelioration and EEG improvement occurred following combined medication of L-Dopa and vitamin B6...


Familial unusual encephalopathy of Binswanger's type without hypertension.

Clinical and pathological studies have been conducted on two brothers with unusual encephalopathy of Binswanger's type. The disease started in the third decade with steady progressive course leading to death in eight or nine years. The clinical picture was summarized as a combination of organic dementia, extrapyramidal disorders associated with pseudobulbar symptoms and marked pyramidal tract signs. The blood pressure remained always normal during the course. Pathologically, there were diffuse and focal demyelination with sparing of U-fibers, multiple small foci of perivascular softening in the cerebral white matter and in the basal ganglia and severe arteriosclerotic changes of memingeal small arteries and long arteries with 100 to 400 micron caliber in the cerebral white matter. Vessel changes consisted of fibrous intimal proliferation, severe hyalinosis and splitting of intima and/or internal elastic membrane. The histopathological process belonged to the category of subcortical arteriosclerotic encephalopathy of Binswanger's type. There has been some discussion as to differential diagnosis among various forms of vasculitis such as cerebral endangiitis obliterans, periarteritis nodosa, systemic lupus erythematosus, rheumatic vascular disease and giant cell arteritis.


Electron microscopic studies of the T-system--the effects of hyperosmolar glycerol and dantrolene sodium on mammalian muscles.

Electron microscopic studies of the T-systems in mammalian muscles were performed to investigate the effects of hyperosmolar glycerol solution and dantrolene sodium. The results indicate that in mammalian muscles the terminal cisterns of the sarcoplasmic reticulum seem to be the site of morphological changes which occur when the muscle specimens were transferred from the hypertonic glycerol solution to isotonic washing solution. When the muscle specimen was further exposed to dantrolene solution, the above changes were intensified. The changes of the terminal cisterns of SR were characterized by prominent vacuolar changes and the T-tubules were pressed and narrowed by those vacuoles secondarily. The glycerol and dantrolene technique did not cause any electron microscopic changes in the sarcolemma, myofibrils, nor Z-discs, and selective changes in the T-system, i.e. at the terminal cisterns of SR were demonstrated. This technique, excitation-contraction uncoupling, abolishes isometric twitch tension up to 99.7% and serves for the purpose of prolonged intracellular recordings of mammalian muscles without movement induced artifacts.


Immunoglobulin abnormalities in epileptic patients treated with diphenylhydantoin.

An immunologic study was made on 170 epileptic patients treated with antiepileptic drugs. The most noteworthy finding was that the serum IgA was decreased in 22 patients, and an IgA deficiency noticed in 12 of them. The blastic transformation rate of lymphocytes in PHA-containing cultures appeared low in seven out of 12 patients. Other findings included decreased serum IgM and IgG in some patients. These abnormalities were not encountered in epileptic patients taking no anti-epileptic drugs. Therefore, they could be considered as the side effects of antiepileptic drugs. In all patients manifesting these abnormalities, diphenylhydantoin was used in common. It was surmised that the above-mentioned immunologic abnormalities caused by anti-epileptic drugs, especially diphenylhydantoin, had resulted from disorders of the antibody producing organs in the bone marrow-thymus-lymphatic system.


[Characterization of active fetal movements in early pregnancy using ultrasound (time-motion technic)].

In 82 pregnancies between 9 and 14 weeks of amenorrhea, 120 registrations of active movements of the embryo were recorded by the ultrasonic time motion technique. Four types of early motility could be observed: Ia = single convulsions of the body, Ib = series of body convulsions, II = rapid movements of the extremities, III = combined complexe movements. The frequency and complexity of the movements increased with progressing gestational age.


[Intensive care in obstetrics and gynecology. Indications for transfer to the intensive care unit].

Between the years of 1969 and 1974, 68 patients were transferred from our Department of Obstetrics and Gynecology to the Intensive Care Unit. This figure represents 0,5% of all operative cases. 50% were high risk patients, previously under the care of our physicians. 11,8% occurred because of problems arising from latent diseases not previously diagnosed. The main reasons for transfer were septic shock, coagulopathy arising from abruptio placenta, placenta praevia, embolism and pneumonia. Interdepartmental cooperation is indispensable for correct diagnosis and a timely transfer.


[Obese patients in obstetrics].

The results of two studies about the course of pregnancy and delivery in adipose women in our hospital are combined and discussed. We found a higher rate of EPH-gestosis in overweight patients. The frequency of Cesarean section was increased. Belated uterine involution post partum is more frequent in adipose women, also the occurrence of urinary tract infections. There is a significant increase in perinatal mortality, mainly due to an increase in still-born. Pneumonia due to aspiration and birth traumata occur more frequently as well and endanger the children.


[Complications following ambulatory abortion].

A survey was made of 394 abortions with ensuing complications during the years 1970-1974. Of these 17 were induced abortions, 3 of which showed serious complications. In two of these cases uterus extirpation by laparotomy was necessary.


[Zeiss Axiomat - a new microscope system].

A new microscope concept is described whereby the individual main functions of a universal microscope are performed by box-type, square-based modules which can be combined at will. The main characteristics of the new Axiomat microscope are the quality of its optics, its universality and stability.


[Epidemiology of endometrial hyperplasia and adenocarcinoma].

In a retrospective study characteristics of 729 climacteric and postmenopausal women with hyperplasia and adenocarcinoma of the endometrium are compared with those of 82 women with atrophic endometrium and 96 women with carcinoma of the cervix. In a prospective study 225 women with glandular-cystic, adenomatous and atypical hyperplasia of the endometrium have been checked by a control-curettage within a period of two months until four years following the first diagnosis. Low parity, disturbances of menstruation with anovulatoric bleedings during fertility period, adipositas, hypertension and diabetes mellitus in climacteric and postmenopausal women indicate a high risk of carcinoma of the endometrium. Hyperplasias of the endometrium in climacteric women cannot be considered as precursors of corpus carcinoma. They are the result of a temporary hormonal dysfunction. Prophylactic hysterectomy, however, should be performed, if adenomatous or atypical hyperplasia appears in older postmenopausal women with the indicators of high risk of endometriumcarcinoma as mentioned above.


[Seat belts and pregnancy].

The best safety for the mother and her unborn child while driving a car is the proper use of a seat belt. Only a correctly constructed and fitted lap-shoulder safety harness should be used. The instruction to wear a seat belt and to wear it correctly should be part of the pregnancy-care-program for each physician.


Perspectives on accountability in mental health and retardation services.

Public mental health and mental retardation agencies are under increasing pressure to demonstrate their accountability in fiscal, legal, program, and other areas. The author discusses some of the problems and issures in pinpointing accountability and identifies eight areas of accountability--to patients, to program and management staff, to a chief executive, to a legislative body, to the public, to one's profession, and to one's self. He describes ways in which accountability can be demonstrated and emphasizes that, for mental health professionals, the overriding issue in accountability must be the provision of high-quality care and treatment for the mentally ill and mentally retarded.


State hospital review boards in Minnesota.

For the past eight years Minnesota has had a review board for each state hospital serving the mentally ill and the mentally retarded. Each board consists of at least three individuals appointed by the commissioner of the department of public welfare. The board is an external review body in that members are not associated with the department or with the state hospital. It visits the hospital as frequently as required to review commitment papers and processes, assess the propriety of treatment procedures, ensure that each patient has an individualized treatment plan, interview patients and record their concerns, conduct a random review of patients' records, and meet with hospital staff. The board reports its findings to the commissioner and to the head of the hospital.


A psychiatrist in a bureaucracy: the unsettling compromises.

Psychiatrists employed by bureaucracies must make a number of compromises in order to reconcile their employing organization's formally stated aims, their superiors' day-to-day expectations, and their traditional role model of physician and patient-oriented therapist. The author studied nine psychiatrists working for the U.S. Army during a two-year period in the mid-seventies. Their adaptation to expectations and pressures of the bureaucracy can be described in one of three general ways: through alignment with the official views of the Army, compartmentalization of roles to meet both patients' expectations and the Army's expectations, or rejection of a military identity.


The politics of program evaluation: the mental health experience.

The authors discuss evaluation studies of the community mental health centers program. The emphasize that program evaluation is a political activity to influence the allocation of public resources. They examine its relationship to decision-making, power conflicts, and bureaucratic goals. They point out that the evaluator is seldom totally objective. They also emphasize the increasing use of evaluation by politicians.


Psychiatric peer review: a working model.

The author describes a system for psychiatric peer review developed by a peer review committee in a general hospital. At the heart of the system is a form called the peer review check sheet, which requires the physician to specify diagnosis, reasons for hospitalization, and major symptom complexes, as well as laboratory work and treatment and discharge plans. Minimal criteria have been established to verify the diagnoses and to justify the need for hospitalization. Each month the check sheets are removed from the charts of patients who have been discharged and sent to committee members for evaluation. Those that are incomplete or unsatisfactory signal the need to examine the patient's chart.


Ribonucleic acid synthesis in normal and immune macrophages after antigenic stimulus.

Macrophage ribonucleic acid (RNA) synthesis is an important metabolic process intimately related to the function of these cells. Mouse peritoneal macrophage RNA was extracted with phenol in the presence of bentonite and electrophoresed on composite agarose-polyacrylamide gels. The pulse-chase technique was used to follow the precursor relationships in macrophage ribosomal RNA (rRNA) maturation. The rRNA species at 18S and 28S appeared at 15 and 45 min, respectively, after RNA synthesis was halted. Their appearance corresponded closely to decreases in the rRNA precursors at 45S, 36S, and 34S. Studies of RNA methylation aided in confirming the identity of these ribosomal species. Unmethylated RNA species appeared as messenger RNA between 5S and 15S, and at about 55S probably represented heterodisperse nuclear RNA. When normal macrophages were incubated with heat-killed Salmonella enteritidis, an acceleration in the maturation of RNA was observed. The accelerated maturation was indicated by the earlier appearance of 28S rRNA and the more rapid development of an equilibrium state, where further labeling did not change the RNA profile. In macrophage RNA from mice immunized with S. enteritidis, rRNA species appeared rapidly but did not accumulate to the same extent as observed for normal macrophages. Precursor rRNA and other RNA species developed as usual, suggesting specific degradation of mature rRNA. Such rRNA wastage could indicate a mechanism controlling ribosome assembly in the non-proliferating activated macrophage. The pattern of RNA synthesis in immune macrophages was essentially unchanged by the presence of heat-killed S. enteritidis in vitro.


Immunoglobulin classes in genital secretions of mycoplasma-infected and normal heifers.

Immunoglobulin levels were studied in the genital secretions of seven heifers which had been bred to a bull infected with Mycoplasma agalactiae var. bovis and three heifers bred to a noninfected bull. The median immunoglobulin G (IgG)/IgA ratio ratio for vaginal secretions was 0.7, for cervical secretions 21.9, and for uterine secretions 13.0. This indicated that IgA was the mahor immunoglobilin class in the most superficial portion of the reproductive tract and that IgG was the major class in secretions of the deeper tract. The response to infection was studied by comparing animals infected with mycoplasma and noninfected controls. The IgG/IgA ratios were significantly lower in infected animals than in controls, apparently due to high IgA values in infected animals. Low mycoplasmal agglutinin titers were detected in secretions of three of the infected animals, but there appeared to be no relationship between agglutinin titers and histopathological lesions or between agglutinin titers and IgG/IgA ratios in this group of animals.


Inactivation of hemolytic complement in human serum by an acylated polysaccharide from a gram-positive rod: possible significance in pigeon-breeder's disease.

In an attempt to identify the major complement-consuming heteropolysaccharides in pigeon excreta, a number of teichoic acids and lipoteichoic acids from gram-positive bacteria were examined as possible substitutes. Teichoic acids from the cell wall and membrane of Lactobacillus buchnerii were found suitable. Samples of freshly voided pigeon droppings were cultured under anaerobic conditions and the bacteria were identified, subcultured, and extracted with phenol-water. Cell wall and membrane antigens from isolated Lactobacillus species could replace pigeon excreta antigens in diagnostic complement consumption tests. Purification and chemical characterization indicated the major antigen from Lactobacillus in this respect to be an acylated heteropolysaccharide.


Endotoxic activity of rough organisms of Brucella species.

A rough-specific antigen extracted from the rough species Brucella ovis and lipopolysaccharide extracted from smooth Brucella abortus demonstrated equivalent levels of activity in tests for mouse lethality and limulus lysate clotting activity. Acetone-extracted whole cells of B. ovis and of B. canis and of a rough mutant of B; abortus had the same toxicity for mice, but it was not possible to extract endotoxin from B. canis by the methods used.


T2 lipopolysaccharide antigen of Salmonella: genetic determination of T2 and properties of the T2, T2,S, and T2,SR Forms.

The T2 antigenic form of Salmonella bareilly was examined. The absence of O specificity in this strain was shown to be due to its nonfunctional rfb genes; when the rfb gene cluster was replaced by the rfb cluster derived from smooth donor strains, T2,S and T2,SR recombinants were produced that expressed both T2 and either 0-6,7 or 0-4,12 specificity, depending on O antigen of the donor strain. The T2, T2,S, and T2,SR forms were all unstable on culture and segregated T2-negative forms (R, S, and  SR, respectively) at a high rate. In all these respects the T2 antigen closely resembled the other T-form antigen, T1. The genes responsible for the T2 antigen, rfu, were not close to rfb, but their precise location and relation to rft (which determines T1 antigen) could not be discovered because of the instability to the T2 form and low recombination frequency in the necessary interspecies crosses.


Lysis of Acholeplasma laidlawii by antibodies and complement.

Membranes of Acholeplasma laidlawii were used to determine the membrane components involved in immune lysis and to eventually detect enzymatic changes in the membrane components during this reaction. In a previous publication we reported that A. laidlawii can be killed by antibody and complement and that antibodies to membrane proteins are by far more effective than antibodies to membrane lipids in the complement-dependent killing of this organism. In this report we demonstrate that membrane damage occurs after the combined action of antibody and complement. In addition, the cytoplasmic enzyme hexokinase is released during immune killing. As visualized by electron microscopy, the organisms lost their cytoplasm and were transformed into ghosts. In the majority of organisms, tears in the membrane could be seen. Ultrastructural lesions of about 8.0 to 10 nm in diameter were visible when the organisms were incubated with antiserum and complement. 14C-labeled fatty acids were incorporated during growth into A. laidlawii membrane lipids. After incubation of labeled organisms with antiserum and complement, release of radioactive material into the supernatant and changes in the lipid composition were not observeed. Enzymatic degradation of membrane lipids of A. laidlawii during immune lysis was not detected.


Rosette-forming cells during immune response to Toxoplasma gondii in mice.

The rosette-forming cell (RFC) response of mice immunized with varying doses of Toxoplasma gondii was studied by immunocytoadherence (ICA). The specificity of ICA in the present system was tested by passive sensitization with hyperimmune serum in vivo and in vitro. A slight increase in RFC was observed with the latter. Prior treatment of spleen cells from immunized animals with rabbit anti-mouse immunoglobulin resulted in total inhibition of ICA. During the primary and the secondary response after 10 days, the number of RFC rose rapidly to reach the peak on the 3rd day. With secondary immunization 30 days later, the peak shifted to the 2nd day. Mice infected with a lower dose of Toxoplasma had a greater number of RFC during the secondary response after 10 days than with a larger dose.


Further characterization of a lipopolysaccharide from Coxiella burneti.

The lipopolysaccharide previously isolated from the rickettsial agent of Q fever, Coxiella burneti, phase I, has been further characterized. The sugar residues ribose, mannose, gluclose, D-glycero-D-mannoheptose, and L-glycerto-D-mannoheptose are present. Two sugars remain unidentified, one of which is a minor and the other a major constituent. Isomyristic, palmitic, and beta-hydroxymyristic acids are the major fatty acid residues of the 15 identified. The nature and content of other lipopolysaccharide constituents are presented.


Diffusible viral interference during arbovirus plaque formation.

A radially diffusing zone of nonspecific interference was observed surrounding plaques of Western equine encephalitis virus. The increase in diameters of the zones of interference were linear and more rapid than increases in plaque diameters. These observations raise the possibility that viral-induced interference could account for the diminished growth of Western equine encephalitis virus plaques with time or even the initial formation of plaques. In addition, this system could be used as a model to study localized host defenses during early infection of solid tissues in vivo.


Differential inhibition of Streptococcus mutans in vitro adherence by anti-glucosyltransferase antibodies.

Antibodies prepared against an insoluble-soluble glucan-synthesizing fraction significantly inhibited in vitro adherence of Streptococcus mutans, whereas antibodies directed against a soluble glucan-synthesizing fraction were much less inhibitory.


Naturally occurring secretory immunoglobulin A antibodies to Streptococcus mutans in human colostrum and saliva.

Human colostrum, parotid saliva, and serum were assayed for the presence of naturally occurring antibodies to five serotypes of Streptococcus mutans. Appreciable levels of agglutinins to strains AHT, BHT, 10449, 6715, and LM-7 (groups a leads to e, respectively) were detected in normal colostrum and saliva, whereas relatively low levels were found in serum. No agglutinins could be detected in the colostrum or saliva of immunodeficient patients. Molecular sieve chromatography of the colostrum on Sephadex G-200 revealed agglutinin activity in the secretory immunoglobulin A (s-IgA)-rich fraction only. Titration of purified colostral s-IgA confirmed the IgA nature of this agglutinating activity. Indirect immunofluorescence tests with anti-s-IgA, -IgG, and -IgM revealed S. mutans specificity only in the s-IgA class. The presence of s-IgA antibodies to indigenous oral microorganisms in colostrum, as well as in saliva, suggests that antigenic stimulation occurs at a site remote from the oral mucosa.


Cell-mediated immunity to Vibrio cholerae with ribonucleic acid-protein fractions of V. cholerae L-form lysates.

Different L-form lysate vaccines of Vibrio cholerae serotypes Ogawa and Inaba and their combination along with ethyl alcohol-precipitated ribonucleic acid (E-RNA) and phenol-extracted RNA (P-RNA) fractions of V. cholerae Ogawa lysates were tested for production of cell-mediated immunity. Both E-RNA and P-RNA fractions induced an increase in leukocyte migration inhibition, macrophage migration inhibition, and macrophage aggregation. They also induced delayed hypersensitivity in rabbits. More consistent results were obtained with the P-RNA fraction.


Cell-mediated immune response to products of Actinomyces viscosus cultures.

Hartley strain guinea pigs were sensitized with 0.5 ml of concentrated cell-free Actinomyces viscosus culture supernatant fluids mixed with Freund complete adjuvant. Fourteen to 16 days later the animals were challenged by intradermal injection with 0.1 ml of the culture supernatant, and the reactions were observed at 4, 8, 16, 24, and 48 h. Peritoneal exudate cells from sensitized animals were used for determination of migration inhibition factor, and guinea pig peripheral blood served as a source of cells for determining the induction of mitogenesis by antigenic material. Skin responses were consistently positive to challenge with the test material, whereas reactions to noninoculated culture medium were negative. Sensitized cells, challenged with antigen, resulted in 60% or greater inhibition of migration of indicator cells in migration inhibition factor experiments. Tests for mitogenesis showed a greater than fourfold increase in isotope uptake when sensitized cells were challenged with test material. The data are consistent with the suggestion that A. viscosus culture supernatants contain substances that induce cell-mediated immune responses in guinea pigs.


Peptido polysaccharide antigens from Trichophyton mentagrophytes var. granulosum.

Two highly purified peptido polysaccharide antigens have been isolated from surface-grown cultures of Trichophyton mentagrophytes var. granulosum. Trichloroacetic acid extraction and ethanol precipitation yielded a mixture containing high-molecular-weight components which were first separated on Sephadex G-200. Subsequent fractionation by ion-exchange chromatography on DE-52-cellulose (borate form) yielded the two peptido polysaccharides. Both of the peptido polysaccharides reacted with rabbit antiserum to T. mentagrophytes var. granulosum. The two peptido polysaccharides contain 73.2% hexoses (mannose-galactose-glucose, 7.5:0.7:1), 8.6% amino acids and 1.8% amino sugars and 77.4% hexoses (mannose-galactose-glucose, 9:0.3:1), 6.2% amino acids, and 0.4% amino sugars, respectively. Each contains 16 different amino acids, threonine, proline, and serine predominating.


Occurrence and distribution of sucrose-metabolizing enzymes in oral streptococci.

Specific growth rates, growth yields, and the level and cellular distribution of three sucrose-metabolizing enzyme activities were determined for seven oral streptococci (Streptococcus mutans strains E49, BHT, 10449, SL-1, and LM-7, S. sanguis 10558, and S. salivarius 25975). Cultures were grown in a fermentor at pH 6 with either 20 mM glucose or 10 mM sucrose. Generation times varied between 21 and 70 min. Whereas some strains grew 10 to 50% more slowly with sucrose than with glucose, others did not. Growth was always logarithmic, and the growth yields were similar. Glcosyl transferase (EC 2.4.1.5) was largely extracellular; in sucrose cultures it was appreciably lower, but no major shift to a cell-associated form was found. In glucose cultures, the activity varied between 4 and 140 IU per 6-liter culture. The glucan formed was mostly or exclusively water insoluble. Glcosyl transferase was stimulated weakly (60% or less) by various dextrans. Fructosyl transferase (EC 2.4.1.10) was primarily extracellular (except in glucose cultures of S. salivarius) and varied between 0 and 337 IU/culture. In S. salivarius, the extracellular fructosyl transferase was induced by sucrose. In all S. Mutans cultures, the total fructosyl transferase activity was lower after growth with sucrose. All strains had extra- and intracellular invertase (EC 3.2.1.26) activity. Total levels varied between 210 and 3,500 IU/culture. Less extracellular activity was present in sucrose cultures. Only S. salivarius had appreciable activity in the cellular particulate fraction. Invertase activity was significantly higher than the combined glucosyl and fructosyl transferase activities in all cultures.


Interaction between Coxiella burnetii and guinea pig peritoneal macrophages.

The phagocytosis and subsequent degradation of phase I and II Coxiella burnetii by macrophages obtained from immune and nonimmune guinea pigs were compared. Phase I rickettsiae were more resistant to phagocytosis than were phase II organisms. There was no significant difference in the percentage of phagocytosis of either phase of rickettsiae by macrophages from immune or nonimmune animals. After ingestion, phase I and II organisms pretreated with normal serum multiplied and destroyed normal macrophages as well as macrophages obtained from guinea pigs immunized with phase II rickettsiae. In contrast, only phase I organisms were degraded by macrophages from phase I-immunized animals in the presence of normal serum. Immune serum rendered rickettsiae more susceptible to phagocytosis and also potentiated the destruction of organisms by all types of macrophages. The specificity of macrophages from phase I animals to degrade only phase I rickettsiae was demonstrated by the ability of Rickettsia rickettsii to replicate in these macrophages.


Antibodies to two immunotypes of Chlamydia trachomatis in individuals with trachoma.

In Tunisia (North Africa), trachoma remains a common eye disease. Most cases are caused by immunotype A of Chlamydia trachomatis. In a small proportion of cases (less than 10%), type-specific antibodies to both immunotype A and immunotype B exist in the serum of patients. These types do not crossreact, and occasionally sequential acquisition of antibodies has been demonstrated. Thus, individuals in one endemic area of trachoma may be infected with two immunotypes of C. trachomatis. The epidemiological and immunological implications of this new finding are briefly discussed.


Serum-free culture of hamster lymphoid cells and differential inhibition of lipopolysaccharide stimulation by isologous serum.

The optimal conditions for serum-free cultures of hamster lymphoid cells were determined. The cells responded to both the nonspecific thymus-derived lymphocyte mitogen concanavalin A (Con A) and the nonspecific bone marrow-derived lymphocyte mitogens lipopolysaccharide (LPS) and dextran sulfate (DxS). Normal MHA hamster serum was shown to specifically inhibit the response to LPS and DxS by 95% without inhibiting the response to Con A. The serum also did not inhibit one-way mixed lymphocyte reaction. Incubation of cells in 5% serum for short periods of time, followed by serum-free culture, did not lead to inhibition. The serum inhibited the LPS response by 65% even when added 24 h after initiation of the culture. The activity was associated with the high-molecular-weight material on Sephadex G-200 fractionation of serum. The inhibitory fraction did not possess antibody activity to LPS. The possibility that the material is an alpha2-macroglobulin is discussed.


Inherited resistance to Corynebacterium kutscheri in mice.

An analysis of the factors responsible for inherited resistance to Corynebacterium kutscheri was undertaken. Various inbred mouse strains were examined; these included the Swiss Lynch and C57Bl/l mice, their F1 and F2 progeny, and the progeny of the F1 backcrossed to each parent strain. Two modes of inherited resistance are described. An examination suggested that resistance as measured by the mean lethal dose of C. kutscheri was under polygenic control and was inherited continuously. However, the efficiency with which C. kutscheri was eliminated by the mononuclear phagocyte cells of the liver over 3 days differed markedly among strains. A genetic analysis of this mononuclear phagocyte microbicidal efficiency (MPME) in Swiss Lynch and C57Bl/6 mice was undertaken. The trait, MPME, was present, but did not segregate, in the F1 progeny or in the progeny of the backcross to the resistant C57Bl/6 parent; this was clear evidence of dominance. Moreover, MPME segregated in a ratio of 1:1 in the progeny of the backcross to the sensitive Swiss Lynch parent and in a ratio of 3:1 in the F2 progeny. It was concluded that MPME was inherited discontinuously and was controlled by a single dominant autosomal gene (or closely linked group); the recessive allele was assigned the gene symbol ack. Linkage experiments showed there to be no association between the ack locus and any of the immune-response genes.


Extracellular and bacterial factors influencing staphylococcal phagocytosis and killing by human polymorphonuclear leukocytes.

Extracellular and bacterial factors that influence the phagocytosis and killing of staphylococci by human polymorphonuclear leukocytes have been studied. Staphylococcus epidermidis strains were, in general, more rapidly phagocytized than were S. aureus strains. However, two strains of S. epidermidis had a very slow rate of ingestion. Although the rate of phagocytosis of S. aureus Wood 46 was greater than that of S. aureus 502A, the Wood 46 strain was more difficult to kill. Serum was essential for phagocytosis of both S. aureus and S. epidermidis. The opsonic titer of pooled serum was similar for S. aureus and S. epidermidis. In normal pooled serum, heat-labile factors were more important for effective phagocytosis than they were in immune serum. Although a saturation point for ingestion was reached, the percentage of ingested bacteria that remained alive within the leukocyte remained relatively fixed. Heat-killed and live staphylococci were igested in a similar fashion. The rate of phagocytosis was greatly reduced at 41 degrees C.


Induction of cellular and humoral immunological responsiveness to a soluble cercarial antigen preparation from Schistosoma mansoni.

The development of immunological responsiveness to a soluble cercarial antigenic preparation (CAP) from Schistosoma mansoni was analyzed in inbred CBA/J mice infected with cercariae, one or multiple times, or sensitized using CAP. Repeated exposure to 75 cercariae at three weekly intervals (3X-75) or subcutaneous administration of 20 mug of CAP (CAP/complete Freund adjuvant [CFA]) stimulated the development of specific anti-CAP lymph node cell blastogenesis. The degree of responsiveness was dependent upon the concentration of CAP in the culture system and was optimal in the dose range of 20 to 30 mug of protein of CAP per culture. Animals exposed once to 75 or 225 cercariae or to two sequential weekly infections with 75 cercariae exhibited a minimal response to CAP in comparison to the responsiveness of 3X-75 or CAP/CFA lymph node cells. Assessment of anti-CAP agglutinating antibody by application of a microtiter passive hemagglutination technique revealed that both 3X-75 and CAP/CFA animals possessed low titers of activity. In addition, both 3X-75 and CAP/CFA sera contained reagin-like antibodies to CAP as detected by the heterologous (rat), 72-h latent period, passive cutaneous anaphylaxis technique.


Analysis of the intradermal response against a soluble cercarial antigenic preparation from Schistosoma mansoni.

Intradermal testing was performed with a soluble cercarial antigenic preparation (CAP) from Schistosoma mansoni cercariae in CBA/J mice multiply infected with S. mansoni or sensitized with CAP. Both an early (5-h) response and a late (24- to 48-h) reaction to CAP, as measured by increase in dermal thickness, was elicited after injection of antigen into the ears of either multiply infected (3X-75) or CAP-sensitized (CAP/complete Freund adjuvant [CFA]) mice. Histopathological examination showed that the early response was primarily vascular in nature and involved a polymorphonuclear cell infiltrate in and around dilated capillaries. The late reaction to CAP consisted of a perivascular cellular infiltrate of polymorphonuclear and mononuclear cell types. Passive transfer of 3X-75-infected or CAP/CFA-sensitized serum (0.4 ml) to normal mice conveyed the ability to mount an early (5-h) response to CAP which was marked histopathologically by a prominent polymorphonuclear cell infiltrate. The majority of the responsiveness in normal mice after administration of lymph node cells (40 X 10(6)) from multiply infected or CAP/CFA-sensitized mice was observed 24 to 48 h after injection of CAP and was mononuclear in nature.


Vibrio cholerae adherence and colonization in experimental cholera: electron microscopic studies.

Colonization of the intestinal epithelium by Vibrio cholerae was examined in two model systems, in ligated ileal loops of adult rabbits and in the patent gut of infant rabbits, using both scanning and transmission electron microscopy. Time studies in the adult model showed a lag period of up to 1 h before the attachment of significant numbers of the vibrios. The bacteria appeared initially in small patches on the sides of the villi, predominantly along the transverse furrows. The number of adherent bacteria steadily increased, reaching a maximum between 4 and 7 h, when a dense mat of bacteria several layers thick covered much of the villi. After this time there was a rapid decline in the number of V. cholerae bound. By 12 to 16 h only a few bacteria could be seen on the surface of the villi, which had a rough, patchy appearance at these later times. Globular protrusions, with vibrios attached, may play a role in the clearance of bacteria. Colonization and clearance in the patent intestine of the infant rabbit occurred much as in the adult model. However, the bacteria adhered more uniformly and there was no lag in attachment. In both models the majority of bacteria were aligned horizontally with the epithelial surface, but some were attached in an end-on manner, with their flagella extending into the lumen. The bacteria adhered via their surface coats directly to the tips of the microvilli, except for a few vibrios that were partly embedded into the brush border. Some changes in the microvilli occurred as a consequence of the bacterial attachment.


In vivo and in vitro studies on possible pathogenic mechanisms of Actinomyces viscosus.

Actinomycotic infections are characterized by long-term inflammatory lesions containing large numbers of polymorphonuclear leukocytes (PMNs) and mononuclear cells. The pathogenic mechanisms involved in these lesions are not understood. Homogenates of Actinomyces viscosus (AVIS) induce an acute inflammatory response with a predominance of PMNs within 6 h after injection into the footpads of nonimmunized mice. These homogenates, when tested in vitro, contain potent chemotactic activity for human PMNs. In vitro chemotactic activity for human monocytes is weak but statistically significant (P less than 0.025). Doses of AVIS, which alone have little chemotactic activity, cause the generation of PMN chemotactic activity in fresh, but not complement-inactivated, serum. The injection of AVIS into the footpads of immunized mice induces an acute inflammatory response followed within 48 h by a mononuclear cell infiltrate, suggesting that factors affecting monocyte accumulation are generated by the immune host in response to challenge with the bacterial antigens. These findings indicate that the pathogenicity of the Actinomyces may result in part from (i) their direct chemotactic effect on PMNs, (ii) their cytotaxigenic effects on serum, and (iii) their ability to stimulate host immune cells to produce and release mediators of inflammation.


Lysis and killing of bacteria by lysosomal proteinases.

The bacteriolytic and bactericidal effects of the human proteinases cathepsin B, cathepsin D, cathepsin G, and elastase were investigated. Cathepsin G and elastase were 5 to 10% as active as egg white lysozyme in the lysis of Micrococcus lysodeikticus. All four enzymes slowly lysed the lysozyme-resistant Staphylococcus aureus. The gram-negative Acinetobacter 199A was rendered sensitive to lysozyme by all of the proteinases. Only elastase caused marked proteolysis of the outer membrane, which would permit access by lysozyme to the underlying peptidoglycan. When the surface layer of regularly arranged a protein was removed, however, the outer membrane proteins became susceptible to the other proteinases. Cathepsin G, elastase, and cathepsin D were bactericidal to Acinetobacter 199A. The bactericidal activity of cathepsin D was shown to be dependent on enzymatic activity, unlike that of cathepsin G, which was related to its cationic nature.


Interferon production in mice by components of Salmonella minnesota R595 lipid A.

The lipid A precipitate obtained by partial hydrolysis in 1% acetic acid of the glycolipid of a mutant strain of Salmonella minnesota (rough strain R595) was separated into a number of components by thin-layer chromatography. When tested as bovine serum albumin complexes, the minimal interferon-inducing dose in mice of the parent glycolipid was 0.1 mug, whereas that of lipid A was 1.0 mug. The minimal dose of the separated components ranged from 0.1 to 20 mug. The components did not differ significantly in regard to glucosamine-phosphate-fatty acid ratios. The results further emphasize that lipid A is a heterogeneous substance that contains a variety of components of differing biological activity.


A comparative study of the economics of home care.

The costs of home care and treatment solely in hospital for patients in a variety of short-term diagnostic categories are compared. Five hundred and eighty-three patients included in an experimental home care program were randomly assigned either to a group which received home care as part of their treatment, or to a control group that remained in hospital the traditional length of time. It is argued that the only costs relevant in an economic comparison of the two modes of treatment are those attributable to the direct care of the patient. A technique is presented whereby changes in the daily amount of nursing service provided can be costed. The economic analysis shows that, when similar diagnoses are compared for an episode of illness, there is basically no difference in cost between home care and treatment in hospital.


The diffusion of new hospital technologies in the United States.

Increases in the real resources used in hospital care have been an important cause behind rising hospital costs in the United States. Many of these resources have taken the form of new hospital technologies, and this paper begins by reviewing the trends in adoption of new hospital technologies over the years 1950-1974. The resource requirements, costs , and to the extent possible the patient benefits, of two of these technologies are then discussed in more detail: intensive care, a widespread facility with many variations, has been a major contributor to hospital costs; radiotherapy has been characterized by a succession of competing technologies. Regulatory efforts such as certificiate-of-need reviews would be more effective if they viewed hospitals as flexible collections of such technologies-with the costs and patient benefits of each to be weighed separately-rather than primarily in terms of numbers of beds. A national center to collect information on the separate technological functions of hospitals and make it available to interested groups would make a useful contribution to hospital regulation.


The service economy and postindustrial society: a sociological critique.

The growth of the service sector in advanced capitalist societies is the empirical evidence in support of the ideological approach to our social systems as "postindustrial." By examining the content of so-called "service activities" and by relating the observed trends to the model of uneven development in the U.S., this article tries to explain the transformation of the social structure of the U.S. on the basis of the contradications inherent in the processes of accumulation of capital, class struggle, and state intervention.


Breast-feeding: the role of multinational corporations in Latin America.

The decline in birthrates in the developed countries of the world has forced multinational corporations engaged in the production of infant formula to seek out new markets in the developing countries, where burgeoning population rates potentially guarantee the long-term profitability of these corporations. This development, ostensibly benign and nutritionally advantageous to infants in developing countries, has serious public health consequences, due to the high relative cost of purchased formula and the paucity of hygienic facilities essential to the sterile preparation of bottle formula. This paper delineates in detail economic and contraceptive advantages of breast-feeding, and examines the role of health personnel and multinational advertising techniques which have catalyzed the decline in breast-feeding. In addition, the paper focuses on the question of cultural imperialism and current efforts to regulate the multinational firms through both United Nations groups and stock-holders' suits. Finally, some suggestions are made concerning ameliorative public policy approaches to the breast-feeding controversy.


Malpractice in the United Kingdom.

The end of the last century saw the development in the United Kingdom of medical protection and defense societies. Their history, objects, growth, and scope are outlined. Reference is made to leading cases of medical malpractice and to the relevant statutes. The relationship between the protection societies and the National Health Service authorities is dealt with and a comparison made of the relative situations in the United States and United Kingdom. Finally, recent trends are examined and views expressed about possible future developments in this field which will be the subject of recommendations by a Royal Commission on Civil Liability and Compensation for Personal Injury which is now sitting.


Nurses and trade unions in Britain.

The nature of the negotiating body for pay and conditions of nurses in Britain and some of the reasons for the body's past failure to negotiate a substantial pay increase for nurses are described in this article. A description is given of a series of events, including strike action by nurses during 1974, which led to a substantial pay raise. The pay award, however, represented only a partial success for the trade unions and the negotiating body. Methods of nurses' organization and the roles of their representative unions and professional body indicate some of the reasons for only a partial success. The lack of unity between the National Health Service trade unions and the reactionary role of the professional body were notable. However, many important political and organizational lessons were learned by nurses in this struggle. We are now facing savage cuts in National Health Service expenditure, leading to a reduction in the number of nurses employed. These lessons are clearly useful for the nurses and their organization with the labor movement in fighting these cuts in National Health Service expenditure.