Radioimmunoassay of human homologous prolactin in serum with commercially available reagents.

A clincally useful and reproducible radioimmunoassay for human homologous prolactin, established with commercially available reagents, was studied and validated. We present detailed conditions for iodination and purification of labeled prolactin and the optimal conditions for the assay. By the method, we found values (microgram/liter) as follows for serum prolactin: normal men. 8.9 +/- 5.2 (mean +/- SD); normal women, 11.8 +/- 5.5; normal women taking contraceptive pills, 9.2 +/- 5.0; pregnant women in the third trimester, 188 +/- 69.5; patients with various diseases other than of the hypothalamic-pituitary axis, 9.3 +/- 6.3; in some patients with amenorrhea and galactorrhea of diverse origin, 78.2 +/- 87.4; and in some patients with surgically proven pituitary tumor, 1414 +/- 1980. Results under provocative testing are also presented for a patient with normal hypothalamic-pituitary function.


Determination of thyroxine-binding globulin in human serum by single radial immunodiffusion and radioimmunoassay.

Two immunochemical methods for determination of thyroxine-binding globulin in human serum were developed, in which the purified globulin and monospecific antiserum to it are used. One method, based on radial immunodiffusion, has good precision and values for analytical recovery. Reference values obtained for men were 9.8-17.8 mg/liter and for women 11.3-20.5 mg/liter. The sex-related difference was significant. The other method is based on radioimmunoassay, with use of an iodinated acylating agent for the labeling of thyroxine-binding globulin. The relative merits of the two methods are discussed.


[Immunochemical determination of human hemoglobin in biological fluids (author's transl)].

An assay of human hemoglobin by immunonephelometry-electroimmunodiffusion is proposed. Concentrations in the range from 5 to 180 mg% can be determined to within 2--5% accuracy. The immunonephelometric assay is independent of the presence of haptoglobin whereas the electroimmunodiffusion assay is not. This immunochemical assay, independent of the peroxydase activity of hemoglobin, can be carried out in any biological fluid (plasma, urine, gastric fluid).


Immunoreactivities of alpha-amylase of humans and rats.

The immunoreactivities of amylase from human saliva and pancreatic juice and rat parotid and pancreas were investigated. Antisera were prepared in rabbits against each of the human and rat amylase. Human salivary and pancreatic amylases reacted similarly with the antibodies to both human salivary and pancreatic amylases. Rat parotid and pancreatic amylases reacted differently with the antibodies to both rat parotid and pancreatic amylases.


Membrane phospholipid composition and anaphylactical response of cardiac and smooth muscle fibers in the Rh (D) system.

The anaphylactical response of sensitized smooth and cardiac papillary muscle fibers as target organs was induced by the stimulation of the complement systems in the antigen-antibody reaction of albumin and anti-albumin. However in the Rh (D) system anaphylaxis was only elicited on smooth muscle segments with the corresponding antigen. This discrepancy between both immune systems cannot be explained only by the fact the Rh (D) anti-D reaction does not stimulate the complement activity. Since this antigen-antibody reaction requires a protein phospholipid interaction, the failure of anaphylactical response on cardiac muscle fibers may be due to its phospholipid environment which differed considerably from that of the smooth muscle fibers. Besides the differences in composition and amount of the phospholipids the fatty acid distribution of phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, cardiolipin derived from cardiac or smooth muscle membranes varied clearly. This may influence the protein phospholipid interaction which is essential for the antigen-antibody reaction of the Rh (D) system.


A method for the determination of amniotic-fluid glycosaminoglycans and its application to the prenatal diagnosis of Hurler and Sanfilippo diseases.

A new and simple micromethod for the determination of individual glycosaminoglycan components in small volumes of amniotic fluid is described. Two-dimensional electrophoresis demonstrated an abnormal content of dermatan and heparan sulphates in amniotic fluid from pregnancies affected by Hurler disease (two at 14 weeks' and one at 16 weeks' gestation), and of heparan sulphate in amniotic fluid from pregnancies affected by Sanfilippo disease (16 and 25 weeks' gestation). Excellent discrimination between normal and affected pregnancies was provided by an estimation of the dermatan sulphate:chondroitin sulphate ratio (Hurler disease) and the heparan sulphate: chondroitin sulphate ratio (Sanfilippo disease); the use of external glycosaminoglycan standards was then unnecessary.


Carbonic anhydrase isoenzyme B in erythrocytes of anemic and non-anemic uremic subjects.

A specific and quantitative immunological method for determination of human erythrocyte carbonic anhydrase isoenzyme B has been used to determine the contents of this enzyme in the erythrocytes from healthy persons and anemic and non-anemic subjects with renal insufficiency. The investigations have shown significant increase of carbonic anhydrase type B in the erythrocytes of patients with renal failure. The erythrocytes of anemic uremic patients have a significantly higher content of erythrocyte carbonic anhydrase isoenzyme B than the erythrocytes of non-anemic uremic subjects. Significant correlations were found between human erythrocyte carbonic anhydrase type B and hemoglobin and between it and plasma bicarbonate. No correlation was found between human erythrocyte carbonic anhydrase and plasma creatinine or creatinine clearance and serum zinc.


Abnormal platelet glycogen metabolism in multiple myeloma patients.

This study presents evidence on the occurrence of an inverse relationship between activation of glycogen synthetase and inactivation of phosphorylase in a platelet preparation in vitro. The activities of glycogen synthetase and phosphorylase and the pattern of changes in these activities in platelets from controls and multiple myeloma patients were compared. Platelets obtained from multiple myeloma patients were shown to have an increased glycogen content, accompanied by an elevated level of glycogen synthetase a and a decreased activity of phosphorylase a. The pattern of changes in these enzyme activities during incubation was also different in platelets of controls and multiple myeloma patients. Extracts from patients' platelets prevented glycogen synthetase activation and phosphorylase inactivation of control platelets. Preincubation of platelets from multiple myeloma patients in control plasma resulted in an increased rate of glycogen synthetase activation, and abolished activation of phosphorylase which was found after preincubation in autologous plasma.


Immunological characteristics of a peroxidase protein in human neonatal cord serum.

Adult serum haptoglobin-hemoglobin complexes exhibit acid-stable peroxidase activity. The haptoglobin level in human neonatal cord sera, however, is reported to be very low. We have isolated a protein from the cord sera of neonates, which has acid-stable peroxidase activity analagous to adult serum haptoglobins-haemoglobin complexes, but does not show any immunological identity to adult serum haptoglobins. It differs from the latter in its molecular size and electrophoretic mobility in agarose and polyacrylamide gels. It is unique to cord sera and it bears immunological identity to human IgG.


Ribonuclease activity in plasma and leucocytes of malnourished children.

RNAase activity was measured in plasma and leucocytes of manourished children. In subjects suffering from kwashiorkor, alk. RNAase levels in plasma and leucocytes were markedly raised and they returned to normal after therapy. However, the enzyme activity was not altered in undernourished children. These data indicate that circulating level of alkaline. RNAase is not a useful parameter for detecting milder grades of protein-calorie malnutrition (PCM).


Haemopexin, caeruloplasmin and C3: effect of diphenylhydantion.

Serum haemopexin and C3 concentrations fell and serum caeruloplasmin rose in 14 epileptic children studied prospectively during treatment with diphenylhydantoin. There was a positive correlation between the changes in haemopexin concentration and those of C3.


The pituitary-thyroid axis following surgery for thyrotoxicosis: thyrotrophin-releasing hormone tests in diffuse thyroid hyperplasia and toxic uninodular goitre.

The pituitary-thyroid axis was assessed 1 month after surgery by thyrotrophin releasing hormone (TRH) testing in thirty thyrotoxic patients treated by subtotal thyroidectomy and eleven patients with toxic uninodular goitre. All toxic nodule patients gave essentially normal TRH responses and have remained clinically and biochemically euthyroid at follow-up. Only seven of the thirty subtotal thyroidectomy patients had normal TRH tests when assessed 1 month post thyroidectomy -sixteen patients showed increased response, six gave flat responses, and one showed an anomalous minimal response. Follow-up TRH tests 12 months postthyroidectomy have shown a tendency for TRH responsiveness to return towards normal, but two patients with flat TRH tests have required radioiodine for relapse and four TRH hyperresponders are currently receiving thyroxine replacement therapy.


Prolactin.

Prolactin exists in man as a distinct and separate anterior pituitary hormone from growth hormone. It is important in lactation and the control of gonadal function, although it may have a much wider and basic metabolic role, similar to its role in lower forms. In clinical endocrinology it is important as an index of pituitary and hypothalamic diseases; thus prolactin levels are elevated in association with these conditions and this reflects the normal tonic inhibitory hypothalamic control of prolactin by PIF; DA is the most important PIF. Hyperprolactinaemia causes hypogonadism in both men and women; it may present in women with amenorrhoea, oligomenorrhoea, polymenorrhoea, regular cycles with anovulation or a defective luteal phase, and impotence in men. In either sex galactorrhoea is reported to occur in only 30 per cent of patients. Neurotransmitter therapy, with dopamine agonists which act as functional analogues of PIF, restores prolactin levels to normal and leads to a return of normal gonadal function. The mechanism of the hypogonadism is not clear and is discussed together with the problems associated with inducing pregnancy in these patients, who may harbour microadenomata of the pituitary.


Thyrotrophin releasing hormone--TSH.

The major determinant of serum TSH and its response to TRH is the interaction of TRH and the thyroid hormones (principally T3) at the level of the thyrotroph. Small changes in thyroid hormone levels within the normal range can produce marked alteration in thyrotroph sensitivity to TRH. Elevated serum TSH is of great diagnostic value in suspected primary hypothyroidism. The demonstration of a normal TSH response to TRH is valuable in excluding the diagnosis of hyperthyroidism, whereas a suppressed response is of lesser value in diagnosis, although characteristic of the hyperthyroid state. TSH responses to TRH are of limited value in the differentiation of hypothalamic from pituitary lesions, and cannot always be correlated with clinical or biochemical thyroid status.


Quantitative measurement of properdin in normal human serum by electroimmunoassay and single radial immunodiffusion.

Properdin in normal serum was measured by electroimmunoassay (EIA) and single radial immunodiffusion (SRID). Fresh sera gave much lower properdin values in SRID in gels containing Mg2+ ions. Storage of sera at 4 degrees C resulted in a gradual increase of the properdin values measured by SRID but not of those of the EIA. With 10 mM of EDTA in the gels no difference between the properdin values obtained by the different methods was found. Evidence is presented that immunodiffusion values of properdin might be affected by precipitation of a C3-properdin complex in gels containing Mg2+ ions after the activation of the properdin system by agarose.


Positive inotropic action of glyceryl trinitrate as observed in the blood-perfused papillary muscle preparation of the dog heart.

1. The effects of glyceryl trinitrate on the coronary vasculature and on the contractility of the ventricular myocardium were investigated by the use of papillary muscle preparations of the dog, and that on the sino-atrial node activity by the use of sino-atrial node preparations of the dog. The papillary muscle preparation was cross-circulated through the anterior septal artery and the sino-atrial node preparation through the sinus node artery from a donor dog. The papillary muscles were driven at a rate of 120 beats/min. Drugs were injected close-arterially. 2. Glyceryl trinitrate, in doses of 0-03-100 microgram, produced dose-related increases in blood flow and developed tension. An increase in developed tension caused by 100 microgram of glyceryl trinitrate amounted to about 24% of the basal developed tension. Large doses of glyceryl trinitrate (100-300 microgram) produced a negative inotropic effect after a positive one in some preparations. 3. The positive inotropic effect of glyceryl trinitrate was not modified by propranolol, excluding a possible participation of an adrenergic mechanism. 4. Glyceryl trinitrate in large doses failed to modify the positive inotropic effect of calcium chloride. 5. Glyceryl trinitrate in a wide range of doses (0-03-100 microgram) had virtually no effect on sino-atrial node activity.


Inheritance of antibody specificity. IV. Control of related molecular species by one VH gene.

Products of two unrelated VH genes or gene clusters of the mouse, VHABA-HOPb and VHNPb, were studied by submitting antisera of immunized mice (either ABA-HOP-immunized or NP-immunized) to an IEF analysis and fine-specificity tests (affinities for a series of structural analogs). Products of both genes had an exotic (heteroclitic) fine-specificity. The products of both genes included several molecular species detectable by IEF (spectrotypes). Some of them were shared by many immunized mice (shared spectrotypes), but others occurred only in one mouse of several tested. Fine-specificity of two shared spectrotypes of the VHNPb gene, N-1 and N-4, were determined. Both were heteroclitic but they differed in nuances of the fine-specificity. Occurrence of different spectrotypes in the course of an NP immunization had a regular pattern. In the primary response, we could detect at least four shared spectrotypes (N-1, N-2, N-3, and N-4). They were predominant in the early response (days 8-14) but less so on day 30. In the secondary response, shared spectrotypes were in the minority, and, in the tertiary response, they had been fully replaced by individual spectrotypes which had a higher affinity for NP than the shared spectrotypes.


Regulation of clonal B-lymphocyte proliferation by anti-immunoglobulin or anti-Ia antibodies.

Regulatory effects of antibodies to cell-surface antigens have been examined in an in vitro clonal assay for B lymphocytes. In this system, cell contact is prevented by a semisolid gel matrix, and many of the factors affecting cell proliferation have been described. Inclusion of antibodies to mu, kappa, or Ia in these cultures reduced the size and number of proliferating foci. As little as 1 microgram/ml of anti-mu antibody prevented formation of colony-size aggregates. Pretreatment with these antibodies before culture followed by wash had no effect. Divalent F(ab')2 anti-IgM antibodies were as effective as intact antibodies, but monovalent Fab fragments were not inhibitory. Anti-gamma1 antibodies, anti-alpha antibodies, or cell-bound antigen-antibody complexes had no effect on clonal proliferation. These findings suggest that a negative signal can be delivered to B cells during a critical period of their activation via certain surface receptors. Modifications in culture conditions result in the selective propagation of different B-cell subpopulations.


On the structure of the T-cell receptor for antigen.

Antigen-binding receptors of T lymphocytes were analyzed in two different ways. First, the idiotypic properties of T helper cells are studied using anti-idiotypic antisera prepared against isolated antibodies specific for A-CHO. These anti-idiotypic antisera are defined by immunogenetic and immunochemical means with respect to their reactivity with heavy- or light-chain-associated idiotypic determinants. Second, antigen-binding receptors are isolated from enriched T-and B-lymphocyte preparations and compared with respect to their reactivity with antigen and with class- or allotype-specific anti-Ig antisera. The results provide an incomplete picture of the T-cell receptor which shares with antibodies the variable region of the heavy chain but probably no other variable or constant portion.


An unusual kappa immunoglobulin antigen present on the membrane of T and B lymphocytes.

Several K immunoglobulin antisera out of a large number studied showed the unique property of reacting with a membrane structure present on all T and B lymphocytes examined. This antigen was detected on lymphocytes by indirect fluorescence, direct fluorescence, and by cytotoxic analysis. Absorption of the antiserum by all K myeloma proteins, K Bence-Jones proteins, and kappa light chains removed the activity; L proteins had no effect. The possibility that the cross-reacting membrane antigen is part of the HL-A system was discussed.


The principles and problems of evaluation.

A multilevel, multifocus approach to evaluation is proposed, using a complex community mental health center as a model. Goal attainment can be evaluated simultaneously from multiple perspectives at several points on the health care continuum, allowing for identification of relationships among diverse goals and for the involvement of varied people who have legitimate contributions to make toward the establishment of these goals. Allowing more people to participate in planning the programs they will ultimately implement, reduces certain barriers to initiating evaluation. The place of evaluation in the program and special skills of evaluators are also considered.


Studies of the squirel monkey, Saimiri sciureus, genome. II. C-band characterization and DNA replication patterns.

Cytological analysis of a squirrel monkey indicates a considerable degree of chromosomal polymorphism. DNA synthetic patterns reveal late synthesis in chromosomal segments that are C-band negative and asynchrony in DNA replication between homologs. Location of a satellite DNA with a CsCl neutral buoyant density of 4.691 g/ml was mainly in the noncentromeric constitutive heterochromatin.


The spectrum of tuberculous peritonitis.

From 1966 to 1973, a total of 30 cases of tuberculous peritonitis were seen in Seattle-King County. Abdominal pain, swelling, and constitutional symptoms were the most frequent initial complaints. Radiographic abnormalities consistent with tuberculosis were present in 25 cases, and pulmonary disease was proven in ten. An initial tuberculin test with intermediate-strength purified protein derivative of tuberculin was negative in 19 of 27 patients. Six of 13 initial nonreactors still had negative reactions on repeat testing, and four appeared to be anergic when retested one to four months later. Ascites was present in 67% (20) of the 30 patients, and laparotomy was used most frequently to establish the diagnosis. Diagnosis was particularly difficult in 13 alcoholics, in whom the disease was usually unsuspected, the findings in the ascitic fluid were uncharacteristic, and negative tuberculin reactions were frequent. Peritoneal tuberculosis was a contributory cause of death in five cases. Three of these patients, who were also alcoholics, went undiagnosed and untreated. Two patients died of unrelated causes. Twenty-three have done well, and 19 have completed chemotherapy.


[Oral iron treatment: intestinal absorption and the influence of a meal (author's transl)].

Intestinal iron absorption after a single dose of a special galenic preparation (50 and 100 mg iron as ferrous glycocoll sulphate in micropellets) was investigated in 105 persons with normal iron stores (42), latent (40) or manifest iron deficiency (23). Absorption rate rate on fasting as well as after breakfast was measured in 21 persons. Intestinal absorption increased in persons with iron deficiency, but maximal absorption after a single dose of 100 mg did not exceed 25%. This absorption rate was already reached in persons with latent iron deficiency. There was no significant reduction of absorption when the preparation was given at the end of breakfast.


[Automatic analysis of long-term EEG in epilepsy. First experiences with a new part-automatic analytic system (author's transl)].

A new equipment for automatic analysis of prolonged EEG derivations is demonstrated. Spikes, waves and SW-combinations are detected and counted separate; counted EEG signals are written with paper speed of 25 mm per sec. Results of a 3-channel-derivation with 1-channel-analysis are shown in a time compressed graphic demonstration. The method gives better information about pathological EEG-signals of one hour or more in epileptic patients, drug effects can be demonstrated easily, and detection of pathological EEG signals is simplified.


[The diagnostic value of the EEG in multiple sclerosis (author's transl)].

245 records of 178 multiple sclerotic patients were assessed from 110 EEG-parameters and 18 clinical points of view. According to the special code the data were stored on cards and later statistically evaluated. The following conclusions were made: 1. 64% of all records were abnormal. 2. The frequency of bilateral and generalized abnormalities was significantly higher with brain stem localization of clinical signs. 3. In the progressiv phase of the disease there was a significantly greater occurrance of bilateral slow EEG abnormalities and bilateral potentially epileptic signs (sharp waves, bilateral paroxysms). 4. Focal EEG abnormality is seldom found in multiple sclerosis.


[Elektro-clinical results in cases with carotis-sinus-cavernosus-fistula (author's transl)].

Eight cases of carotid cavernous fistulas are reported. Electroencephalograms were done before, during and after operative attack und during digital carotid compression. Preoperative, there was a mild general slowing, ipsilaterally marked in the parieto-temporal region. During digital carotid compression slowing may be found on the opposite side because of a steal syndrome. The degree of these physical changes and of those during hyperventilation depends on the individual cerebral blood flow and the corresponding situation of cerebral blood flow and the corresponding situation of cerebral metabolism. These changes are especially marked under anaesthetics. That is why derivations under anaesthetics seem to be most important for indicating the operation and to be correlated to the functional disturbances by the fistula. delta-activity is no contra-indication, when faster activity is superposed. Seizure potentials, only, seem to be a contra-indication. Pathogenetic mechanisms of electroencephalographic changes are being discussed. From that can be concluded that early operative treatment is necessary. Especially if the patient is young, there may be no need for compression training. Simultaneously, there is a possibility for curing neuro-ophthalmic disturbances.


[The EEG in hypercalcemia (author's transl)].

The EEG of 20 patients with hypercalcemia of different aetiology were investigated. (Hyperparthyreodism n = 14; Carcinomas with metastases n = 5; plasmocytom n = 1). General abnormalities were observed in most cases in different severity with a decrease of frequencies (n = 13) and an abnormal periodicity (n = 9). Beside one case there was a positive correlation between serum-calcium-level and EEG-abnormalities. Abnormal EEG-findings were observed mostly above serum calcium levels of 6,5 mval/1 = 13 mg%. There was a marked normalisation of EEG with decreasing serum-cacium-level. Different factors dealing with these abnormal EEG findings in hypercalcaemia were discussed.


[Electrophysiogical and neuropharmacological studies in a patient with progressive myoclonus-epilepsy (author's transl)].

A progressive form of myoclonus-epilepsy was described in an 21 year old girl. Electrophysiological and neuropharmacological studies were carried out. The typical EEG-pattern, the close association of cortical discharges and myoclonic jerks, the form of myoclonus indicated a "pyramidal" myoclonus. Pharmacological data suggested that two possible mechanisms--a partial deafferentation of cortical neurones and a failure of thalamic, extrapyramidal and brain stem reticular formations--might be responsible for the EEG-abnormalities and concomitant myoclonus. Results from neuropharmacological studies demonstrated a suppressive effect (on EEG-discharges and myoclonic jerks) of clonazepam, diazepam, phenobarbital, taurine, levodopa and budipin. Taurine, levodopa and budipin might induce a new aspect in therapy of progressive myoclonus epilepsy and of myoclonus caused by other etiologic factors.


[Intraveneous therapy of petit mal status with diazepame and clonazepame (author's transl)].

Interrupting petit-mal status in infantile myoclonic seizures (n = 11), Lennox syndrom (n = 32), and in myoclonicastatic petit mal (n = 13) diazepame (Valium) and clonazepame (Rivotril) have been injected intraveneously in 56 patients during continuous EEG monitoring (38 patients with diazepame, 18 patients with clonazepame) (Table 1). A judgement according to the EEG findings and the apparent vigilance was performed thirty minutes after the injection was completed (Fig. 1 und 2; Table 3). Following results are presented: 1) There are no significant differences between clonazepame and diazepame with respect to therapeutic success (Table 3). 2. There are almost no differences concerning therapeutic success in the three forms of petit-mal status listed above (Table 3). 3) The initial success was 57%: 46% in infantile myoclonic seizures, 56% in Lennox syndrome, 70% in myoclonic-astatic petit-mal. The number of relapses for all forms was high: On the day following the injection only 18% of all patients did not show continued petit-mal-status: 18% in infantile myoclonic seizures, 15% in Lennox syndrome, 23% in myoclonicastatic petit mal (Table 3). 4) 13 patients were no longer in a status on the following day. 3 children were out of status spontaneously, independent from the intravenous application, 4 patients, one with infantile myoclonic seizures and 3 with Lennox syndrome, showed a focal EEG, 6 patients, 2 with infantile myoclonic seizures, 3 with Lennox syndrome, 4 with myoclonic-astatic petit mal, were further demonstrating generalised paroxysms (Fig. 1 und 2). 5) In infantile myoclonic seizures and in the Lennox syndrome almost always a focal EEG could be seen that accompanied the decrease of generalised paroxysms (hypsarrhythmia or 2/sec slow wave and spike). This finding has not been seen in the myoclonic-astatic petit mal, another sign that the latter is of primary generalised, "centrencephal" origin in contrast to the first two forms of convulsive disorders (Fig. 1, 2).


[Determination of the normalized slope descriptors in the time Zusammenfassung and frequency domain (author's transl)].

Hjorth's EEG parameters are computed. 1. using a method in the time domain (realized in a hybrid manner by means of an analog computer), 2. by means of spectral analysis. The concordance is within the range of the precision of measurement. With this result Hjorth's descriptors present themselves for parameter reduction of the EEG-spectra.


Separation of functional and non-functional beta subunits of thyrotropin preparations by polyacrylamide gel electrophoresis.

Electrophoretic patterns of intact human and bovine TSH and bovine LH can be clearly distinguished from those of their subunits in 12% polyacrylamide gels, thus providing an easy method of examining subunit recombination. Two distinct components of both bovine and human TSH-beta subunits are observed, of which only one recombines with alpha subunits. Both beta-components cross-react with antisera to TSH and TSH-beta and have, within experimental error, identical amino acid compositions. Thus, the non-recombining component is a non-functional form of TSH-beta which has retained its immunological specificity, and the data explain why the recovery of biological activity during the recombination of TSH subunits is substantially less than with several other glycoprotein hormone preparations.


Microsomal hexose-6-phosphate dehydrogenase in injured liver.

Hexose-6-phosphate dehydrogenase (H6PD) in rat liver microsomes was clearly differentiated kinetically, immunologically and electrophoretically from glucose-6-phosphate dehydrogenase (G6PD) localized in liver supernatants. Although the soluble G6PD activity increased upon liver injuries induced by CCl4 and thioacetamide, the H6PD activity decreased markedly 1-2 days following administrations of these hepatotoxins. The specific activity of H6PD remained fairly constant under other experimental conditions where the levels of the soluble G6PD activity increased.


Purification and characterization of the phosphorylated DNA-binding protein from adenovirus-type-2-infected cells.

The virus-coded  72000-Mr DNA-binding protein from adenovirus-type-2-infected cells has been purified to homogeneity by DEAE-cellulose chromatography, selective precipitation and gel filtration. The 72000-Mr DNA-binding protein is phosphorylated and the phosphate is covalently linked predominantly to serine. Analysis of tryptic digests of the 32P-labeled 72000-Mr protein showed that the phosphate residue(s) is present in only one peptide. The DNA-binding fraction contains an additional non-phosphorylated protein with an approximate molecular weight of 45000. Tryptic peptide maps of [35S]methionine-labeled 72000-Mr and 45000-Mr polypeptides are indistinguishable. The amino acid compositions of the 72000-Mr and 45000-Mr polypeptides show closely related distributions. An antiserum produced against the purified 72000-Mr DNA-binding protein precipitates both the 72000-Mr and the 45000-Mr protein from extracts of adenovirus-infected cells. Immunofluorescence studies revealed DNA-binding protein to be accumulated in characteristic structures in nuclei of the infected cells.


Characterization of the protein moiety of messenger ribonucleoprotein complexes from duck reticulocytes by two-dimensional polyacrylamide gel electrophoresis.

The protein moiety of duck globin messenger ribonucleoprotein complexes isolated by oligo(dT)-cellulose chromatography or by sucrose gradient centrifugation was analysed by two-dimensional polyacrylamide gel electrophoresis under conditions where the separation in the first dimension occurs according to charge and in the second according to molecular weight. By comparing the pattern of protein from the mRNA - protein complex with that of ribosomal subunits we found that two acidic proteins with an identical molecular weight of about 49 000 and three basic proteins of about Mr 56 000, 64 000 and 73 000 were associated with the duck globin mRNA but were absent from either puromycin/high-salt-derived or 'run-off' ribosomal subunits. The comparison of the proteins from the complex with mRNA with those found in the 0.5 M KCl wash, commonly used as the source of initiation factors, showed also that only the 49 000-Mr protein from the complex could possibly be present in the 0.5 M KCl wash of polyribosomes; proteins with mobilities similar to the other three proteins complexed with mRNA were not detected in the salt wash of polyribosomes.


Translation of enzymically decapped messenger RNA.

An enzymic procedure was used to remove the 7-methylguanosine diphosphate moiety at the 5' ends of rabbit hemoglobin mRNA and mouse immunoglobulin light-chain mRNA. Evidence was obtained that the procedure, which involves the use of polynucleotide kinase, does not result in any further degradation of the mRNA. The enzymically decapped mRNA was as effective as untreated mRNA in supporting protein synthesis in a wheat germ system. This was the case over a wide range of mRNA concentrations and over a considerable period of time. The presence in the incubation mixture of S-adenosylhomocysteine, an inhibitor of methylation, did not affect the results. The data indicate that the presence of a 7-methylguanosine diphosphate residue at the 5' end of mRNAs is not an obligatory requirement for translation in eucaryotic systems.


99mTc-Sn oxine complex: a radiocompound with possibilities for lymphographic studies.

A very simple method of preparation of 99mTc-Sn oxine which shows a high yield of radioactive labeling is described in this paper. After intravenous injection the radiocolloid is taken up mainly by the reticuloendothelium. The subcutaneous administration indicates a good migration through the tissues and a high accumulation by lymph nodes, characteristics which point to the usefulness of this radiocompound for lymphographic studies.


Hemodynamic and angiocardiographic changes following nitroglycerin in coronary artery disease.

33 patients with suspected coronary artery disease were studied hemodynamically and angiocardiographically in the resting state and following administration of 0.4 mg of sublingual nitroglycerin (NTG). After NTG several parameters were changed: LVEDP, mean LV systolic pressure, EDVI, ESVI, SVI and SWI were decreased; EF, mean Vcf, MNSER, heart rate (P less than 0.01; r = 0.801) and chords, hemichords and shortening of long axis were increased. However, the changes after NTG were markedly different in patients with diffuse and localized LV asynergy, suggesting a more important inotropic effect of NTG in patients with localized LV asynergy, while reduction in venous return and EDV would be the main effect of NTG in patients with diffuse LV asynergy.


A reassessment of intravascular volume measurements in protein--calorie malnutrition.

Accurate determination of plasma volume is difficult in oedematous protein--calorie malnutrition, but present studies on the equilibrium of labelled red cells have shown that red cell volume measurements are valid in this syndrome. The red cell volumes have been measured in afflicted Bantu children during a refeeding programme. Expression of the results in ml/kg, ml/m2 or ml/cm is misleading and has been replaced by expressing the results as a percentage of the means of the normal values for the height. The results show that the red cell volume increase that ought to occur at the end of refeeding programme (and hence the iron requirement) is far higher than suggested by the packed cell volume. With treatment the red cell volume increases slowly. The red cell volume and plasma volume changes that occur during treatment do not take place at the same rate.


Influence of glucagon on natriuresis and glucose-induced sodium retention in the fasting obese subject.

The role which glucagon could play in the mechanism of fasting natriuresis and renal sodium retention associated with carbohydrate refeeding was studied in thirty-seven non-diabetic obese subjects. In nine obese subjects undergoing a 7 day fast without any additional treatment (control group), the renal sodium excretion exceeded intake through the whole experimental period, with maximal natriuresis on day 2 of the fast. Blood glucose and plasma insulin (IRI) levels fell rapidly from the first day of fast on, while pancreatic glucagon (IRG) titres rose from day 1 to day 4, declining slightly thereafter. When additional subjects received intravenous glucose on day 4 (n = 6), there was a rise in blood glucose concentration and in IRI associated with a rapid drop in IRG restricted to the period of glucose infusion. The resulting antinatriuresis occurred essentially during the following 36 h, while IRG and IRI levels had returned to fasting levels. A comparable glucose load on day 4 associated with 0.1 mg glucagon (n = 5) still led to the glucose-induced antinatriuresis while 1 mg glucagon added to a similar glucose infusion completely abolished its antinatriuretic effect (n = 6). Glucagon infused alone on day 4 of fast aggravated fasting natriuresis (n = 5) but was devoid of this effect when administered 24 h after the glucose load (n = 6). These data indicate that fasting hyperglucagonaemia or its reduction upon glucose refeeding, cannot be considered as directly involved in renal mechanism(s) responsible for fasting natriuresis of antinatriuretic effects of carbohydrate. It is suggested that the role of glucagon is indirect, possibly through its influence on ketogenesis which in turn may alter renal sodium handling.


Composition of the glomerular basement membrane in the congenital nephrotic syndrome of the Finnish type.

The composition of the glomerular basement membrane (GBM) was studied in three patients with the congenital nephrotic syndrome of the Finnish type (CNF). A decrease was found in the relative amounts of amino acids characteristic of collagen, i.e. 3-hydroxyproline, 4-hydroxyproline, hydroxylysine and glycine. The decrease of hydroxyproline was also apparent in the ratio of 4-hydroxyproline to proline and in direct assays of 4-hydroxyproline in whole glomeruli. The ratio of 3-hydroxyproline to 4-hydroxyproline was decreased by about 40%. Slight increases were found in the amounts of some amino acids. No significant change was found in the glucose content of the GBM whereas the galactose content was slightly decreased. The results suggest a decrease in the relative amount of the collagen component in the GBM of CNF patients, but a decrease in the relative amount of 3-hydroxyproline indicates that other changes also exist.


Differences in heparin-released lipolytic activity in the superficial and deep veins of the human forearm.

Various doses of heparin were given as a single injection into the brachial artery of each of twelve fasting healthy males. Plasma lipolytic activity was measured in samples obtained before and at frequent time intervals after heparin injection, in the artery and the deep and superficial veins of the same forearm. As little as 0.15 U heparin produced a rapid and detectable release of lipolytic activity in both deep and superficial veins. A series of tenfold increases in the dose produced correspondingly greater releases in the veins but the increments in the release were smaller than the increments in the dose. Three repeated 15 U doses of heparin, separated by 30 min, in the same subject gave a high degree of reproducibility of the release of lipolytic activity in both deep and superficial veins. 90% of the lipase activity in the vein was inhibited by 1 M NaCl. In all subjects the release of lipolytic activity was higher in the deep vein, which predominantly drains muscle, than in the superficial vein, which drains mostly subcutaneous tissues such as skin and adipose tissue. This indicates that muscle is a tissue of considerable importance as a source of post heparin plasma lipolytic activity.


Plasma secretin concentration in man: effect of intraduodenal glucose, fat, amino acids, ethanol, HCl, or ingestion of a meal.

The effect of infusing isotonic saline, isotonic and hypertonic glucose, fat emulsion, amino acids. ethanol, and hydrochloric acid into the duodenum on the plasma concentration of immunoreactive secretin was studied in seven normal subjects. Only hydrochloric acid showed any effect. After acidification of the duodenum with hydrochloric acid a significant rise in plasma secretin concentration was observed from 1.3 +/- 0.4 pmol X 1(-1) (mean +/- SEM) to a peak value of 13.0 +/- 1.2 pmol X 1(-1) after 5 min. The concentration returned to the basal level within 15 min. In eight other normal subjects the plasma secretin concentration was measured after the ingestion of a protein-rich meal. No significant changes were observed during the 2 h postprandial period.


Possible sites of interaction of acute renal failure with amino acid utilization for gluconeogenesis in isolated perfused rat liver.

Experiments were performed to elucidate the mechanisms involved in the enhanced conversion of amino acids to glucose in acute uraemic rats. Increased gluconeogenesis from a mixture of serine, threonine, lysine, glutamate, ornithine and citrulline was confirmed using a non-recirculating perfusion system. Stimulation was concentration dependent, being most pronounced at physiological amino acid concentrations. Stimulation of glucose and urea formation could be mimicked by using serine alone whereas with lactate and pyruvate inhibition of gluconeogenesis was observed. Serine dehydratase activity was significantly elevated following nephrectomy. Further, the uptake of the non-metabolize amino acid alpha-aminoisobutyrate was considerably increased. It is concluded that serine may play a special role as substrate for the additional glucose formation in acute uraemic rats, probably mediated by an activation of serine dehydratase. Acceleration of amino acid transport seems to represent an additional component of stimulation of amino acid utilization in acute uraemia.


Total serum haemolytic complement activity, erythrocyte sedimentation rate and plasma fibrinogen as indicators of the stage in Hodgkin's disease.

Total serum haemolytic complement activity, plasma fibrinogen, erythrocyte sedimentation rate and other biological values in forty-three patients with Hodgkin's disease were correlated with results of staging. A highly significant increase (P=10(-5)) of the mean total serum haemolytic complement activity was found in stages IIIA and IVA and in all stages with systemic symptoms. The complement activity in patients with less extensive disease without systemic symptoms (stages IA and IIA) did not show a significant increase over the controls. The best initial parameters correlating well with disease activity were complement activity, ESR and fibrinogen level. It is concluded that total serum haemolytic complement activity gives additional information and can be helpful in differentiating between favourable and unfavourable forms of Hodgkin's disease.


Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.


Serum gastrin response to acute and chronic hypercalcaemia in man: studies on the value of calcium stimulated serum gastrin levels in the diagnosis of Zollinger-Ellison syndrome.

In this study the effect of calcium infusion over 3 h without gastric aspiration on serum gastrin was determined in fifteen normal subjects, ten patients with duodenal ulcer, nine with stomal ulcer, five with total gastrectomy, six with achlorhydria and sixteen with proved or presumed Zollinger-Ellison (ZE) syndrome. Serum gastrin only rose significantly in the patients with ZE-syndrome or achlorhydria. An increase of above or below 50% of basal value seems to be a valuable criterion by which to differentiate between patients with and without ZE-syndrome. Serum gastrin levels in forty-four patients with chronic hypercalcaemia (72+/-24 pg/ml, mean+/-SD) were not significantly different from the levels in 100 normal subjects (66+/-18 pg/ml; P greater than 0.10). However, in one patient with ZE-syndrome and in two patients with achlorhydria serum gastrin values were markedly higher during chronic hypercalcaemia than during normocalcaemia. It is concluded that acute or chronic hypercalcaemia without gastric aspiration does not lead to hypergastrinaemia in the absence of ZE-syndrome or achlorhydria.


Effect of physical exercise on erythrocyte lipids, biliary cholesterol and bile lithogenicity in rats.

Male Wistar rats were exercised (E) by daily 1 h swimming for 24 days. Sedentry controls (S) were caged individually. Bile analysis at the end of the experiment (24 h after the last exercise) showed a decrease in bile cholesterol (CH) (P less than 0.02) and phospholipids (PL) (P less than 0.01) in the exercising animals, but no significant change in the bile acids (BA). These changes in the exercising rats resulted in a decreased CH saturation of bile: in an improvement in the (BA + PL)/CH ratio (P=0.05) and a trend to a decrease in the per cent saturation of bile CH. Exercise did not affect the bile flow or bile acid flux rate. Exercise decreased erythrocyte phospholipids (P less than 0.01). The effect of exercise on bile was associated with a trend to lower CH in the erythrocytes and in the adipose tissue and thus most likely does not represent a shift of cholesterol from the liver to the peripheral tissues. Physical exercise may be a preventive factor in cholesterol gallstone formation.


Characterization of a carcinogen-induced murine B lymphocyte cell line of C3H/eB origin.

A carcinogen-induced lymphoid tumor, denoted 38C-13, obtained in a T cell-depleted mouse of C3H/eB strain, was adapted to continuous culture in vitro and characterized with respect to its cell surface components. The cells possess IgM class immunoglobulins on their surface but do not secrete it. This membrane IgM is composed of mu and L-chains that are similar in apparent molecular weight to those of an IgM myeloma protein. It is also homogeneous as revealed by isoelectric focusing. The cells possess Fc receptors but lack complement receptors as well as Thy-1 and Ia alloantigens. These characteristics indicate that 38C-13 cells are transformed counterparts of small B lymphocytes at an early stage of differentiation.


Cortical cells projecting to the dorsal column nuclei of rhesus monkeys.

Corticals cells projecting to the dorsal column nuclei (DCN) of Rhesus monkeys have been identified after unilateral or bilateral injection of horseradish peroxidase (HRP) into the dorsal medulla. HRP-positive neurons identifiable as the source of cortico-DCN projections were pyramidal cells in layer V whose largest diameters ranged from 12--31 micron. Cortico-DCN neurons were concentrated in the trunk, fore- and hindlimb regions of area 4 and of SI, and to a lesser extent in SII. This distribution is comparable to the topographical distribution of cortico-DCN neurons in cats. However, cortico-DCN neurons in monkeys are also numerous in at least part of the supplementary motor cortex and in area 5. The results suggest that cortical neurons in several different cytoarchitectonic areas may exert direct control upon cells in the DCN and that the functional role of cortic-DCN projections ought not be view as a simple "feedback" system.


Functional linkage between the electrical activity in the vermal cerebellar cortex and saccadic eye movements.

The temporal relation between the onset of electrical activity of Purkinje cells and the occurrence of rapid eye movements was studied. Experiments were performed in unanesthetized animals, the recordings being made under direct vision through the use of a chronically implanted teflon sleeve. The following results were obtained. 1. Correlation between the activity of Purkinje cells and eye movements indicates that Purkinje cell firing in vermal lobules VI and VII precedes eye movement by 11-12 msec, peak activity corresponding to the time of onset of eye movement. 2. This eye movement related activity of Purkinje cells occurred regardless of the direction of the eye movements but some cells showed directional biases. Best correlation between eye movement and Purkinje cell activity was found with fast eye movements toward the right regardless of recording side. 3. Electrical activity of Purkinje cells was mainly related to saccades. Slow eye movement modulation, although probably present, was not studied in detail. 4. In those cells where an extensive set of measurements could be made, Purkinje cell firing was found to be inversely proportional to the amplitude of the eye movement, small movements being preceded by highest Purkinje cell activity. The present results suggest that cerebellar vermis responds prior to the generation of eye movement and may probably serve to control eye movements in a ballistic manner.


Convergent projections of different limbic vocalization areas in the squirrel monkey.

The projections of four different sub-areas within the anterior limbic cortex, all yielding vocalization when electrically stimulated, were compared in six squirrel monkeys by the autoradiographic tracing technique. Areas of convergence of the projections from all four vocalization loci were the cortex within the anterior cingulate sulcus, a zone following the inferior thalamic peduncle from the central amygdaloid nucleus through the substantia innominata into the midline thalamus, a second zone following the periventricular fibre system from the anterior diencephalon to the caudal midbrain and dorsolateral pontine tegmentum and, finally, the tail of the caudate nucleus. Except for the latter, all of these brain structures produce vocalization when electrically stimulated. The call types elicitable from these projection areas are sometimes different from those elicitable from the anterior limbic cortex. It is hypothesized that the anterior limbic cortex controls vocalization directly, independently of the specific motivational state underlying it.


Comparative morphometric study of the cells of the third proximal segment of the rat kidney under different conditions of fixation.

The morphometric study of the P3 segment of rat proximal tubule has shown that neither the method of fixation, nor the fixative itself, significantly change the relative and absolute volumes of the cell compartments, provided that the fixation media are made approximately isotonic.


Hemisphaericin-D, a dialysable and polymerizable protease found in Bromelia hemisphaerica.

Proteolytic activity was detected outside dialysis bag filled with Bromelia hemisphaerica fruit juice. The dialysable protease was concentrated and purified from small molecular weight contaminants on Sephadex G-10 columns. Acrylamide gel electrophoresis of the dialysable protease, in the presence of SDS and 2-mercaptoethanol, demonstrated a single protein band of about 8000 daltons mol. wt. The same single band with identical mobility was shown with Hemisphaericin, the enzyme retained inside the dialysis bag. The small protease, named Hemisphaericin-D was antigenic in rabbits and the antibodies cross-reacted fully with Hemisphaericin. Hemisphaericin-D appears not to be a degradation product of Hemisphaericin.


Immunochemical studies on acetylornithine 5-aminotransferase from Pseudomonas aeruginosa.

Mouse antibodies with specificity towards acetylornithine 5-aminotransferase (ACOAT) from Pseudomonas aeruginosa were used to study the structural similarities of several isofunctional enzymes from different sources. With the antibody directed against ACOAT, the amounts of enzyme present in cells grown under different conditions were determined. These experiments established that the enzyme is induced by arginine and is subject to repression by carbon sources.


Reduction of adenylylsulfate and 3'-phosphoadenylylsulfate in phototrophic bacteria.

Extracts of 14 species of phototrophic bacteria, partly grown with different sulfur compounds, were tested for their ability to form volatile sulfur compounds from adenylylsulfate (APS) and 3'-phosphoadenylylsulfate (PAPS). The Rhodospirillum species showed marked activities with both APS and PAPS while the Rhodopseudomonas species seem to prefer PAPS. The Chromatiaceae exhibited the strongest activities with APS, whereas Chlorobium limicola had equally high activity with PAPS.


Responses of skeletal muscle fibres to lanthanide ions. Dependence of the twitch response on ionic radii.

A study of the effects of the lanthanide series of ions on toad skeletal muscle fibres reveals that they a) inhibit the twitch response, b) exhibit a marked dependence on ionic radius, and c) apparently exert their effects on the sarcolemma.


Receptors for polymerized albumin on liver cells.

By the use of rabbit polymerized albumin labelled with fluorescein isothiocyanate, or coated on sheep red blood cells, specific receptors on rabbit liver cells were demonstrated. The possible biological role of these receptors is discussed.


A tissue-selective prostaglandin E2 analog with potent antifertility effects.

N-methanesulfonyl 16-phenoxy-omega-tetranor PGE2 is a prostaglandin analog which is markedly more tissue selective than PGE2. This compound is 10-30 times more potent than PGE2 in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE2.


Scanning electron microscopic observation of spermiophage cell within the lumen of the epididymal duct of the vasectomized Japanese monkey (Macacus fuscatus).

The spermiophagic process by intraluminal macrophages in the epididymal ducts of the vasectomized Japanese monkey was well visualized with scanning electron microscope. The fragments of disintegrated spermatozoa were seen in the phase enveloped in bulk by flap-like cytoplasmic extensions or in the phase ingested within the cytoplasm.


Changes in the T4/T3 molar ratio following thyrotropin releasing hormone injection in cattle.

The injection of thyrotropin releasing hormone into cattle resulted in a rapid decrease in the T4/T3 molar ratio. 2 breeds of cattle, Shorthorn and Africander Cross were studied. The decrease in the T4/T3 molar ratio was significantly greater in the Shorthorn breed. It is concluded that acute stimulation of the thyroid gland with TRH results in enhanced release of both T3 and T4 and that T3 is discharged more rapidly than T4.


A facile one-step synthesis of cysteinyldopas using mushroom tyrosinase.

A convenient one-step procedure, based upon the tyrosinase co-oxidation of dopa and cysteine, is reported for the synthesis of 5-S-cysteinyldopa (I) in 74% yield. Secondary products of the reaction turned out to be 2-S-cysteinyldopa (II, 14%), 2,5-S, S-dicysteinyldopa (iv, 5%), and the hitherto unknown 6-S-cysteinyldopa (III, approximately 1%).


Mathematical model of pituitary thyrotropic function.

A nonlinear differential equation is used to develop a mathematical model describing the time course of thyrotropin (TSH) concentral to real data shows that pituitary responsiveness to TRH is highest in euthyroidism, reduced in primary hypothyroidism, and lowest in hyperthyroidism.


Comparative ultrastructural study of mast cells in mastocytoma and mastocytosis.

The ultrastructural aspects of mast cells from skin lesions in 2 patients with mastocytoma were compared to those from lesions in 4 patients with mastocytosis, 3 with cutaneous and 1 with systemic involvement. In mastocytoma, the mast cells accumulated in a large mass. They revealed short cytoplasmic villi and were similar, morphologically, to mast cells of normal skin and gingiva. In the diffuse types of the disease, cutaneous and systemic, the cells were arranged in small groups. In addition to normal mast cells, there were also irregular or bizarre-shaped cells presenting long and twisted cytoplasmic protrusions. In the case with the systemic involvement and in 2 of 3 cases with apparently cutaneous diffuse lesions, the villi of adjacent cells interlaced and showed a tendency to form mast cell aggregates. The pathognomonic value of the above observation seems worthy of further investigations.


[Effects of nitroglycerin on pressure-volume diastolic relationships of the left ventricle in patients with coronary disease].

In fifteen patients with coronary artery disease who underwent hemodynamic studies, pressure measurements and left ventricular angiography were performed prior and 5' after the administration of 0.4 mg of spray nitroglycerin (TNG). Two different expressions of left ventricular diastolic compliance (dV/dP - V at end-diastole, delta V/delta P normalized by end-systolic volume-VTS) were assessed in basal conditions and after TNG. Nitroglycerin decreased left ventricular end-diastolic pressure (control 22.7 +/- 7.6 mmHg; TNG 11.4 +/- 6.1 mmHg, p less than 0.001) left ventricular end-diastolic volume (control 138 +/- 54 ml/m2, TNG 122 +/- 54 ml/m2,  p less than 0.001) and improved compliance indexes (dV/dP - VED control 1.3 +/- 0.5 10(-2)/mmHg; TNG 4.6 +/- 4.3 10(-2)/MMHg; p less than 0.01; delta V/delta P - VTS control 0.071 +/- 0.04 mmHg-1; TNG 0.170 +/- 0.14 mmHg-1, p less than 0.01). TNG decreased the average value of modulus of chamber stiffness K (control 0.031 +/- 0.009; TNG 0.028 +/- 0.008, p less than 0.02) shifting the pressure-volume curve in some patients rightward and downward. Thus the increase of end-diastolic compliance (dV/dP - VED) is due to preload reduction and in patients who presented a marked decrease in K, also to the shift of the pressure-volume relation. These effects of TNG have important implications because they permit patients with coronary artery disease to engage in a given effort at a significantly lower end-diastolic pressure, avoiding pulmonary congestion.


Mammary tumor and leukemia in male Sprague-Dawley rats evoked by a series of intragastric administration of 7,12-dimethylbenz(a)anthracene.

A series of administration of 7,12-dimethylbenz[a]anthracene given at biweekly intervals by gastric intubation of juvenile male rats of the Sprague-Dawley strain elicited considerable number of mammary carcinomas, leukemias, and ear duct tumors. The evoked leukemia shared two main types; 51.6% of erythroblastic stem cell and 48.4% of myelogenous.


Spontaneous rupture of the esophagus. Report of two cases successfully treated by intravenous high caloric nutrition and review of 59 cases collected from Japanese literature.

For the period from 1951 through 1975, 4 cases of spontaneous rupture of the esophagus have been successfully treated at the IInd Department of Surgery, Tohoku University Hospital, Sendai, Japan. Two cases of them conservatively treated with intravenous high caloric nutrition were reported. Fifty-nine Japanese cases of spontaneous rupture of the esophagus were reviewed. Symptoms, diagnosis, treatment and prognosis of the disease were discussed.


Carrageenan in formula and infant baboon development.

Male and female infant baboons were reared from birth to 112 days of age on infant formulas containing concentrations of carrageenan varying from none to 5 times the concentration in commercially available formulas for human infants. Carrageenan content of the formula did not affect weight, characteristics of urine and feces, findinds on physical examination, hematological variables, blood chemical analyses, organ system weights, or the macroscopic and microscopic appearance of the gastrointestinal tract.


Early perivenular sclerosis in alcoholic fatty liver: an index of progressive liver injury.

Alcoholic steatosis was associated with sclerosis around the terminal hepatic venules in liver biopsies of 40% of chronic alcoholics but not in those of moderate drinkers. To determine whether this sclerosis could be a precursor lesion of cirrhosis, controlled studies were performed in animal models. In the alcohol-fed baboons that developed fibrosis or cirrhosis, progressive perivenular sclerosis invariably started at the fatty liver stage before or even more commonly in the absence of alcoholic hepatitis. No sclerosis occurred in controls or in alcohol-fed baboons and rats that did not progress beyond the fatty liver stage. The clinical and experimental data indicate that sclerosis around the terminal venules, a common but often overlooked complication of alcoholic fatty liver, reflects heavy prolonged drinking, and may identify those patients who are susceptible to develop the more advanced lesions of alcoholic liver injury upon continued drinking.


Hepatic infarction and diabetic ketoacidosis.

A 36-year-old man with brittle diabetes mellitus developed hepatic infarction immediately after an episode of ketoacidosis. The infarction was documented by angiogram 99mTc sulfur colloid scan, and biopsy. Except for the association with ketoacidosis, no other possible cause of hepatic infarction was found.


Pseudomembranous enterocolitis in childhood.

Pseudomembranous enterocolitis is reported in five children. The clinical syndrome, characterized by the acute onset of profuse diarrhea, occurred postoperatively in 2 patients. All the patients had received or were taking antibiotics (penicillin, ampicillin, clindamycin). The disease was severe in 4 persons who presented with hypoproteinemia. Related complications were edema, ascites, pleural effusion, septicemia and/or shock. The diagnosis was made on the basis of typical rectosigmoidoscopic findings. Despite intensive therapy 2 children died. The use of parenteral nutrition is advocated in severe cases with exudative enteropathy. When profuse diarrhea occurs postoperatively or does not rapidly subside with discontinuation of antibiotic therapy, a high index of suspicion should be maintained, even in children, for the possibility of pseudomembranous enterocolitis. An emergency rectosigmoidoscopy should be done in order to make an early diagnosis.


Genetic and cytogenetic analysis of the Adh region in Drosophila melanogaster.

Eighteen Adh-negative mutations were selected with 1-pentyn-3-ol after feeding of formaldehyde. Twelve of the 18 were shown by cytological and genetic analysis to be deletions. Cytological examination of the deletions allowed us to localize the Adh gene to a region including bands 35B3-5 on the left arm of chromosome 2. The deletions were also used to order known visible loci located near Adh.--The vital loci near Adh were also investigated. A total of 109 lethal mutations were generated with EMS and 33 of these, localized within a region defined by the overlap of two of the deletions, were found to belong to 13 complementation groups. If one includes three other loci known to belong there (el, Adh and Sco) a total of 16 complemetation groups have been identified in the region close to Adh.


Evidence for a set of closely linked autosomal genes that interact with sex-chromosome heterochromatin in Drosophila melanogaster.

It is proposed that there exists a special region in the euchromatin of the left arm of chromosome 2 (contained within sections 31-32 of the standard salivary gland chromosome map) that is defined by a set of genes, each one of which interacts with a specific sex-chromosome heterochromatic segment. The evidence for the existence of this region is, first, the exhibition, mapping, and analysis of five different maternal-effect, embryonic semi-lethals located in region 31-32. Secondly, in each case the consequence of the maternal effect is markedly influenced by the amount of X- or Y-chromosome heterochromatin carried by the progeny of mutant mothers. The nature of this interaction and possible reasons for the existence of the cluster of autosomal genes are discussed.


Accumulation of deleterious genes in a cage population of Drosophila melanogaster.

Lethal and sterility mutations were accumulated in a cage population which was initiated with lethal- and sterility-free second chromosomes of D. melanogaster. It took about 2,000 days for the frequencies of these genes to reach equilibrium levels, i.e., 18% lethal and 9% male-sterile chromosomes. Two other cage populations which were initiated with random chromosomes sampled from natural populations and kept for more than eleven years in the laboratory showed 19-20% lethal content. The elimination rates of lethals by homozygosis in these populations were smaller than the mutation rate. By using NEI's formulae, the deleterious effect of a lethal gene in heterozygous condition (h) was estimated to be 0.035. The effective population number in the cage populations was estimated to be 1,000-2,900, while the actual population number was 3,500-7,800.


[Analgos of riboflavin, lumiflavin and alloxazine derivatives. II. Effect of roseoflavin on 6,7-dimethyl-8-ribityllumazine and riboflavin synthetase synthesis and growth of Bacillus subtilis].

The replacement of 8-CH3 group in the riboflavin molecule results in the formation of specific antimetabolites. They are rozeoflavin, 7-desmethylrozeoflavin, 8-amino (nor) riboflavin, 8-ribitylamino (nor) riboflavin. Effect of rozeoflavin and other riboflavin analogues on the growth and regulatory characteristics of Bacillus subtilis strains with different genetic state of riboflavin operon is studied. Roseoflavin at a concentration of 0.05 mkg/ml inhibits DRL synthesis in rib-b110 strain. An analogue inhibits the growth of auxotrophic and prototrophic strains at concentrations of 0.5 mkg/ml and 50 mkg/ml respectively. Riboflavin (1 mkg/ml) recovers the growth of bacteria. The curve of rozeoflavin regulation of DRL and riboflavin synthetase synthesis is shifted in 100 times in the direction of lesser concentrations as compared with riboflavin and 8 amino (nor) riboflavin. 180 mutants resistant to 100 mkg/ml of rozeoflavin were selected. 150 mutants over-synthetize riboflavin.


[Effect of calcium and magnesium ions on different stages of genetic transformation in Bacillus subtilis].

Optimal concentrations of magnesium and calcium ions under their combined effect on genetic transformation in Bacillus suttilis are 2 - 10(-2) M and 4 - 10(-2) M respectively. The same concentrations are optimal under the effect of each cation clone. Magnesium ions are efficient during irreversible DNA binding. In the presence of magnesium ions calcium ions stimulate more late stages of transformation. The greatest efficiency of transformation is shown in consecutive effect of magnesium ions at early stages of transformation and of calcium ions at late transformation stages. This suggests that magnesium and calcium ions stimulate the activity of nuclease, taking part at early and late transformation stages.


Antibiotic activity of pyrenomycetes under submerged conditions.

Twenty-three pyrenomycete species were tested for antibiotic activity in submerged cultures. When they were screened against bacteria and fungi, 15 showed positive results. Among these, Eutypa acharii, Diaporthe pustulata, Melanconis flavovirens and Camarops microspora were quite promising against bacteria and/or fungi. An antibacterial antibiotic from Camarops microspora was partially purified and characterized.


[Therapy of the bronchitic syndrome in the elderly].

The prophylactic means and general modes in the treatment of the bronchitic syndrome in geriatric patients are outlined. The therapy is discussed with respect to the use of broncholytics, secretolytics and steroids on the basics of a detailed lung function test. The altered health condition of the geriatric patient needs an intensive and detailed therapy program and must include limitations caused by the old age.


Effect of bromocryptine on the secretion of thyrotropic hormone (TSH), prolactin (Pr), human growth hormone (HGH), thyroxine (T4) and triiodothyroxine (T3) in hypothyroidism.

Bromocryptine (CB-154) virtually abolished the rise of serum Pr after TRH stimulation in hypothyroid and euthyroid subjects. The response of serum TSH to TRH stimulation was significantly depressed in hypothyroid but not in euthyroid subjects. No significant changes of serum HGH, T4 and T3 after CB-154 were observed. The dual mode of action of CB-154 in pituitary and hypothalamus is discussed.


Suppression of luteinization in the baboon by thyrotrophin-releasing hormone (TRH).

Parenteral administration of 40 microgram of synthetic thyrotrophin releasing hormone (TRH) which began two days prior to ovulation and continued for four days suppressed the luteinization of corpus luteum as judged by the lower level of plasma progestin. In contrast, injections of saline had no effect. Simultaneous injections of 300 microgram of synthetic LHRH in TRH treated baboons brought about a resumption of postovulatory rise of plasms progestin. Injections of TRH in the early luteal phase did not suppress the postovulatory rise of progestin. It is, therefore, inferred that injections of TRH suppress the midcycle LH rise and subsequently suppress the luteinization of corpus luteum, rather than exerting a direct effect on the ovary of the baboon.


[Modification of urea-N and creatinine levels using need-adapted amino acids during parenteral nutrition in patients under intensive care].

The present retrospective study concerns two sub-groups of patients having normal serum creatinine levels, adequate 24-hour urine volumes and no pathological changes in the serum or urine osmolarity. There are differences in the initial values of the serum urea nitrogen, the higher (with almost 60 mg%) being already in the azotemia range. Both sub-groups received 100 g of an amino acid mixture adapted to requirements in addition to comparable parenteral nutrition. This did not lead to non-physiological changes in urea nitrogen or any of the other parameters measured in either of the groups. The findings obtained allow the following conclusions to be drawn: Parenteral administration of a quantity of essential and non-essential amino acids adapted to requirements did not bring about a rise in urea nitrogen in either the patients with normal or raised urea nitrogen values. Hence there are not grounds for assuming that in the post-operative or post-traumatic phase the use of a mixture of essential amino acids is necessary to reduce potentially occurring azotemia.


Activation of complement by opportunist pathogens and chemotypes of Salmonella minnesota.

Washed cells of Staphylococcus aureus, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Salmonella minnesota chemotypes (S, Rb, and Re) were tested for their ability to activate the alternative complement pathway (ACP). Parameters of ACP activation were (i) conversion of C3 in 10 mM ethyleneglycol-bis-(beta-aminoethyl ether)-N,N1-tetraacetic acid-treated human serum supplemented with 2.5 mM MgCl2, (ii) lysis of glutathione-treated human erythrocytes in the presence of human serum, and (iii) C3 to C9 consumption in C4-deficient guinea pig serum. With the exception of S. minnesota Re and S. aureus, all of the strains were highly active in the test systems when compared with inulin. S. minnesota Re and S. aureus initiated C3 conversion in untreated human serum, suggesting that these microorganisms were capable of activating complement by a mechanism other than the ACP. These results provide direct evidence for ACP activation by opportunist gram-negative bacilli and refute the hypothesis that the lipid A moiety of the lipopolysaccharide cell wall is responsible for ACP activation.


Rabies virus glycoprotein. II. Biological and serological characterization.

Purified rabies virus glycoprotein (G) was shown by complement fixation and immunodiffusion tests to be a second distinct antigen of the virus. It it the only structural protein of the virus that induces the formation of virus-neutralizing antibodies and which confers immunity to animals. When the G protein is taken as antigen, the complement fixation test can be used for the assay of virus-neutralizing antibodies. The total protective activity of the virus was recovered in the purified G protein preparation. The protective activity of G protein increased with purification: 9 ng of G protein was required to protect 50% of the mice as compared to 1.63 micrograms of the virus. Selective immunofluorescent membrane staining and immunocytolysis of rabies virus-infected cells were shown to be G protein specific. Due to its purity and potency, the G protein preparation can be considered the ideal human antirabies vaccine.


Immune response and dental caries incidence in Streptococcus faecalis-monoassociated Harvard caries-resistant and caries-susceptible rats.

Harvard caries-resistant rats (CR) monoassociated with cariogenic Streptococcus faecalis (SF) for 150 days developed early high levels of specific SF serum agglutinins, moderate levels of salivary antibody, and little or no caries activity. Harvard caries-susceptible (CS) SF-monoassociated rats developed serum antibody more slowly and never reached the titers of the CR group. Little or no salivary agglutinin was found, and extensive caries developed. Second-generation monoassociated CR rats (CR-2) born to SF-monoassociated CR parents showed an immune response and caries activity more nearly resembling those of the CS rat than those of their CR parent. The CR rat appeared to be a high responder and the CS rat, a low responder to viable antigen on the mucous surfaces in both serum and salivary antibody production. Immunization by parenteral injection of killed SF cells produced equally high serum titers in both CR and CS strain rats, but failed to increase salivary agglutinin titers in any group or to protect against caries. These data suggest that there may be an immunologic basis for genetic differences in caries susceptibility between CR and CS Harvard rat strains and that this difference has been modified by some factor in the environment of the CR-2 rats.


Effect of anti-mu-chain-specific immunosuppression on Chikungunya virus encephalitis of mice.

Mice neonatally immunosuppressed with anti-mu antiserum failed to produce circulating antibodies to sheep erythrocytes and showed a marked decrease in circulating immunoglobulins. However, when they were intracerebrally infected with Chikungunya virus (a group A togavirus), they showed a mortality rate consistently lower than non-immunosuppressed control mice. Several possible explanations for this finding are discussed.


Biological properties of Rickettsia prowazekii strains isolated from flying squirrels.

Four strains of Rickettsia prowazekii, isolated from flying squirrels (Glaucomys volans volans) from Florida and Virginia, were compared with other strains of the typhus biotype, two previously established strains each of R. prowazekii and R. typhi and one strain of R. canada, for similarities in a number of unrelated phenotypic characteristics. R. akari served as a spotted fever biotype control. All strains produced small plaques on chicken embryo cell monolayers that were clearly recognized only after 10 days of incubation at 32 degrees C. All strains were highly susceptible to erythromycin. The Renografin density gradient centrifugation procedure of separating rickettsiae from the infected yolk sacs of surviving chicken embryos was equally satisfactory in all cases and resulted in moderate to large yields of purified rickettsiae. There was relatively small variation in specific hemolytic activity or specific CO(2) formation from glutamate. None of the strains catabolized glucose. There was some strain variation in virulence for the chicken embryo, but none of the above tests separated the three species of the typhus biotype. On the other hand, R. akari was clearly distinguished by its more rapid plaque formation and by higher resistance to erythromycin. It is concluded that by the tests conducted thus far, the biological properties of the flying squirrel strains do not differ substantially from those of other strains of the typhus biotype.


Kinetics and maintenance of acquired resistance in mice to Listeria monocytogenes.

In the mouse system, acquired resistance to Listeria monocytogenes can only be demonstrated after immunization with viable microorganisms. A successful state of immunity cannot be elicited with formalin-killed organisms or bacterial cell-derived products. Viable, serologically cross-reactive organisms (not mouse pathogenic) do not induce a state of immunity as measured by acquired resistance. The duration of immunity, once established, is dose independent, and the absolute interval of its existence is not extended by secondary challenge with large numbers of viable organisms. The decline of immunity in actively immunized animals is not altered by antigenic challenge with formalin-killed cells or cell products. This indicates that the cellular requirements for the development of host resistance are similar for induction as well as maintenance. In vitro measurements of cellular immunity by migration inhibition indicate that formalin-killed organisms as well as cell products were recognized by actively sensitized lymphocytes obtained from immune animals.


Comparative evaluation of human leukocyte and fibroblast interferon in the prevention of herpes simplex virus keratitis in a monkey model.

The prophylactic potency of topically applied human leukocyte interferon and human fibroblast interferon was compared in a monkey model with herpes simplex virus type 1-induced keratitis. Both interferons effectively prevented keratitis at 1.9 X 10(6) U of activity per ml but were ineffective at 1.9 X  10(3) U/ml. Slight differences between human leukocyte interferon and human fibroblast interferon observed at the level of 1.9 X 10(5) U/ml were not statistically significant.


Direct evidence for the presence of lipopolysaccharide components in Pseudomonas ribosomal vaccine.

The presence of sugars specific to lipopolysaccharide, glucose, and rhamnose was demonstrated in a Pseudomonas ribosomal vaccine. The detection of these sugars was accomplished by radiological means after paper chromatography of the neutral fraction of acid-hydrolyzed vaccine.


Differential sensitivity of Xeroderma pigmentosum cells of different repair capacities towards the chromosome breaking action of carcinogens and mutagens.

The sensitivity of cultured fibroblasts obtained from four unrelated Xeroderma pigmentosum patients (XP-K, XP-C, XP-E and XP-H), which showed different DNA repair levels, was examined. The frequency of metaphase plates with chromosome aberrations and the frequency of breaks and exchanges per chromosome complement were estimated following exposure to the carcinogens 4-nitroquinoline-1-oxide (4NQO),N-acetoxy-2-acetyl-aminofluorene (N-acetoxy-2-AAF), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and to the mutagen daunomycin. The frequency of chromosome aberrations (breaks and exchanges) increased in the order (XP-K less than XP-C less than XP-E less than XP-H) with decreasing DNA repair capacity of the XP cells examined (XP-K greater than XP-C greater than XP-E greater than XP-H) following 4NQO and N-acetoxy-2-AAF. MNNG induced DNA repair synthesis and chromosome aberrations in the four XP cell types at levels comparable to those in fibroblasts of non-afflicted persons. Daunomycin triggered no DNA repair synthesis but induced similar frequencies of chromosome aberrations in the XP cells and controls. Heterozygous XP cells from parents of XP-K, XP-E and XP-C responded as control cells towards the three carcinogens and the mutagen used. Xeroderma pigmentosum can be considered to be an "induced" chromosome instability syndrome, in contrast to Bloom's syndrome or Fanconi's anaemia, which are "spontaneous" chromosome breakage syndromes according to German's definition.


Visor osteotomy and vestibuloplasty--a one-stage procedure. A preliminary report.

The visor osteotomy as described by HARLE gives a considerable increase of the absolute height of the atrophic mandible, between the mental foramina. After 6 weeks a total vestibuloplasty with mucosal grafting (and a lowering of the floor of the mouth) is performed. A method is described in which the visor osteotomy and the vestibuloplasty are performed in one stage.


Behavior of cortical bone grafts under different types of fixation.

The fate of cortical bone grafts, rigidly fixed by means of a special metal splint, was studied in rabbits. Cortical grafts of fresh autologous bone were compared with dry-stored allogenous transplants frozen to -20 degrees C. To study the incorporation and remodeling, fluorochrome labeling and microradiography were used. The main parameters of remodeling were the quantities of old lamellar bone, newly formed lamellar bone, and vascular spaces present in the transplant areas. The data obtained are compared with the results of a previous similar study of grafts, which were fixed by Mersilene sutures. Fresh autologous as well as allogenous (dry-stored, frozen to -20 degrees C) cortical bone grafts, used as free transplants, show the same type of incorporation and ultimately the same amount of remodeling. Rigid fixation is a valuable contribution in promoting primary function.


Mandibular condyle dislocation into the middle cranial fossa.

A case is reported of a woman aged 25 with a dislocation of the right mandibular condyle into the middle cranial fossa. The most striking clinical feature is a strongly limited mandibular movement and the fixation of the mandible in the dislocated position. Adequate radiographic examination including tomography is necessary to obtain the proper diagnosis and to determine the position of the condyle and the displaced bony fragments of the cranial base. Early diagnosis and treatment are very important for a successful reposition. In the described patient manual reposition of the dislocated condyle was obtained 2 days after trauma. The risk of intracranial complications makes close cooperation with a neurosurgeon necessary.


Absolute augmentation of the mandible.

In spite of all the attempts that have been made so far to bring about an absolute augmentation of the mandible, this procedure remains more or less at the experimental stage. The greatest difficulty in the known techniques is that the transplanted bone is resorbed to a great extent in a relatively short time. In the last 2 years at our department we have developed a new technique in which the resorption has up to now been minimal. Bone is no longer transplanted subperiosteally on the alveolar process, but the resorbed mandible is split into cranial and caudal portions from the region of the left 3rd molar to the region of the right 3rd molar, and between these two fragments the bone transplant is placed. In this way the resorption after 2 years is practically nil and, moreover, the patient can wear a normal prothesis.


Condylar fractures of the mandible. II. a radiographic study of remodeling processes in the temporomandibular joint.

Remodeling processes in 76 temporomandibular joints were studied on radiographs from 67 individuals sustaining condylar fractures. The indivuduals were ranged into four age groups: 3-11, 12-15, 16-19, and larger than or equal to 20 years of age at the time of fracture. The radiographic examinations were to be performed at the time of the trauma and 3, 6, 12, 24 and 36-48 months after the injury. In the age group 3-11 there was a complete return to normal skeletal relations in 20 of the 27 joints. Joints in teenagers (12-19) did not become normal to the same extent and in adults only minor remodeling was observed. In children the remodeling of the condylar process was extensive but indistinctly outlined. With increasing age there was a shift towards a more distinct apposition of bone on the posterior part of the condylar head visualized as a double contour. This contour first appeared in the late teens. In adults the remodeling processes seemed only to be part of the functional adjustment. Thus, the remodeling processes of the condylar process in a clinical sense may be looked upon as restitutional in children and adjusting or functional in adults. As regards the articular fossa, in children the remodeling processes were first observed as a double contour, of which the new one became more and more distinct, while the original roof gradually disappeared. The final results was a flattened fossa. In adults, a sclerosis of the roof of the fossa was found.


Condylar fractures of the mandible. III. positional changes of the chin.

Positional changes of the chin (symphysion = sy) following unilateral condylar fractures of the mandible were studied in 21 children and 20 adults by means of repeated radiographic examinations. On each occasion and for each individual the actual position of the sy was related to an estimated normal position. In those children in whom the remodeling processes in the temporomandibular joint (TMJ) resulted in normal skeletal relation, the result of the subcondylar fractures seemed to be a deviation of the sy towards the nonfractured side. In cases of condylar head and neck fractures a deviation towards the fractured side frequently occurred. In four of the five children in whom normal skeletal relation in the TMJ was not obtained, the sy deviated towards the condylar fracture side. In the majority of the adulsts, a deviation towards the condylar fracture side occurred irrespective of the level of the condylar fracture.


Treatment of mandibular fractures by means of stable internal wire fixation.

Treatment according to the principles of stable internal fixation offers great advantages for fractures of the mandibular body. Most authors believe that a stable internal fixation can be achieved only by means of bone plating or screw fixation. At Groningen a wire connection was designed by BRONS which could be considered to be stable. The application of this stable internal wire fixation and the results of treatment in 272 fractures of the mandibular body between 1967 and 1976 are discussed.


Bilateral surgical removal of impacted mandibular third molar teeth as a model for drug evaluation: a test with oxyphenbutazone (Tanderil).

Twenty-four healthy patients undergoing two separate operations for removal of an impacted third molar from one or the other side of the mandible, were included in a double-blind crossover study. On the two occasions either oxyphenbutazone (Tanderil) or placebo was given for 5 days, commencing on the day before surgery. Plasma analyses confirmed drug intake. A number of objective and subjective assessments were recorded for a paired comparison of the postoperative course, including swelling, trismus, local temperature and pain. On the 1st, 3rd and 5th postoperative days after the oxyphenbutazone-operation, the measured swelling averaged 86, 85 and 83%, respectively, of that after the placebo-operation; the corresponding P-values were less than or equal to 0.11, 0.03 and 0.06. Oxyphenbutazone did not significantly reduce the local hyperpyrexia. It exerted, however, an excellent pain relief, which may have contributed to less trismus and patient preference for the course with this drug. The results obtained with this model in humans showed considerable discrepancies with the analgesic and anti-inflammatory effects ascribed to oxyphenbutazone from results in animal models. Side effects were mild and infrequent, and no unfavorable effects on bleeding or wound healing were noted. Routine use of oxyphenbutazone in oral surgery, however, is not recommended.


Immunochemical investigations of human pituitary beta-lipotropin.

Antiserum to human beta-lipotropin has been raised in rabbits and characterized by gel double diffusion, quantitative precipitin, microcomplement fixation and biological neutralization tests. A sensitive radioimmunoassay for human beta-lipotropin has been developed. It was demonstrated that the antiserum shows specificity for this hormone. Human beta-melanotropin and human beta-endorphin showed only a minimal degree of cross-reaction, while ovine beta-lipotropin showed a partial but significant degree of cross-reactivity.


Descending optic nerve degeneration in primates.

We cut the optic nerve at the orbital apex in squirrel monkeys to study the descending degeneration of optic nerve axons and their ganglion cell bodies. We could not detect progressive disintegration of the axon from the site of injury back to the cell body. Instead, the entire length of individual axons seemed to degenerate simultaneously as early as 3 weeks and as late as 6 weeks after injury, as judged both by ultrastructural integrity and by continued slow axonal transport, a reflection of local physiologic function. We could not relate the time of degeneration to the distance of the injury from the cell body. Evidently there is a signal of injury to the cell body after axotomy, though the nature of the signal and the mechanism by which it leads to cell death are unknown.


Peroxidase permeability of the cryogenic chorioretinal adhesion.

Under normal conditions the retinal pigment epithelium does not permit passage of peroxidase tracers. Photocoagulation disrupts this barrier. Rhesus monkeys which received transconjunctival cryotheropy showed a similar disruption, with leakage of horseradish peroxidase into the retina. This leakage persisted for the 6-month duration of the experiment. One month after treatment, a firm chorioretinal adhesion was present, characterized by gliosis, adherent junctions, and cellular interdigitation. The anatomic features of the cryogenic chorioretinal adhesion were similar to those previously described in human eyes.


Changes in health care ideology in relation to self-care by families.

Health care is shifting from a professional-independent to a business-bureaucratic orientation. Both professional and business ideology have been unfavourable to the development of self-care and a strong health care role for families. But business ideology contains more loopholes for the emergence of a higher level of family self-care activity. The shift forces consumers to take a cautious posture in the marketplace, encouraging active management of their own health care. However, families will obtain government support for their self-care activities and a policy-influential role in health system governance only through organized political action.


Research and demonstration issues in self-care: measuring the decline of medicocentrism.

Emergence of consumer health self-care is a reflection of the increased commitment of health professionals to patient education, growing consumer awareness that they are capable of sophisticated self-help, and a variety of social, economic and technological currents. These currents are reviewed and a survey of existing medical self-care programs is summarized. The attempts and potentials to evaluate these programs are critically examined. A number of important research and demonstration issues are raised including the determination of behavioral outcomes, technical limits, and manpower implications. A federal program of replicative studies on such issues would provide substantive knowledge in the self-care field, generalizable to the larger field of health education, but the hazards of undermining the voluntaristic and non-establishment character of the programs must be considered in designing evaluative studies.


The pattern of loci on Drosophila chromosomes.

In this study, we have attempted to detect and describe patterns in the arrangement of gene loci within chromosomes of a metazoon. Known loci (842 of them) on the first three chromosomes of Drosophila melanogaster have been characterised according to a list of 45 properties and the distributions of these properties have been examined systematically. For all these properties, there is little, if any, evidence of clustering between known loci that are not close enough to belong to the same 10-locus group. Our analysis has, however, revealed evidence confirming that some properties show a tendency to cluster within a 10-locus group. Even this tendency is not strong, except for some of the morphological properties. However, it is apparently at variance with the findings of Elston and Glassman (1967), based on fewer data.


Selection acting upon slow-migrating ADH alleles differing in enzyme activity.

Relative egg to adult viability was compared in three stocks of Drosophila melanogaster differing in alcohol dehydrogenase (ADH) activity. Two of these, Grell's standard ADHS and a mutant ADHS strain producing half the normal number of ADH molecules, had the same electrophoretic mobility. The experiment demonstrated a correlation between survival in alcohol-supplemented media and enzyme activity. This supports the hypothesis that enzyme activity per se, rather than some other attribute of allelic differences, may be responsible for the previously observed selective advantage of high activity alleles on alcohol media.


Polymorphism at two loci through selection for linear metric deviation.

A model of phenotypic stabilising selection in which the fitness of an individual depends solely on its phenotype, and not directly on its genetic constitution, is explored algebraically for a system of two linked loci of unequal effect. It is found that selection for metric deviation gives rise to polymorphic gametefrequency equilibria for a variety of  fitness regimes. Stability of non-trivial equilibria occurs for a wide range of parameter sets. Stability is facilitated by close linkage and inequality between gene effects. It is suggested that, in general genetic variation may be maintained under stabilising selection when the fitness of double heterozygotes exceeds that of the phenotypically intermediate homozygotes.


Genetical composition, temperature, density and selection in an enzyme polymorphism.

Selection in egg-to-adult viability was investigated at the Esterase-6 locus of Drosophila melanogaster. A factorial experiment was carried out with three variables, temperature, density and genetical composition; there were four temperatures (15 degrees, 20 degrees, 25 degrees and 30 degrees), three densities (115 ml, 10 ml and 2-5 ml of food). Strong frequency dependent selection was observed in many environments. The strength of the selection was very much modified by an interaction between temperature and density. The results are discussed in relation to evidence for a chemical mechanism which mediates frequency dependent selection, by conditioning, in the larval environment.


Esophageal patch grafting as a treatment for esophageal stricture in a horse.

Esophageal patch grafting, using the sternocephalicus muscle, was used for treatment of cervical esophageal stricture in a mare. The mare was maintained during the initial healing phase by total parenteral nutrition.


Effects of serum lipid content on the binding of minocycline.

Minocycline was added to normal and hyperlipemic serum samples in concentrations of 1 approximately 10 mcg/ml. These specimens had similar protein contents. Chemically extractable minocycline was quantitated fluorometrically. Hyperlipemic serum (cholesterol 480 mg/100 ml; triglycerides 321 mg/100 ml) yielded an average of 50% less minocycline than did normal serum (cholesterol 170 mg/100 ml; triglycerides 114 mg/100 ml). When ultrafiltrates of serum containing 6, 12 and 20 mcg/ml minocycline were assayed microbiologically, it was evident that variations in serum triglyceride and cholesterol levels did not alter the ratio of bound to free drug. Minocycline appears to be reversibly associated with, and/or soluble in, triglyceride-cholesterol components of serum.


The treatment of enteric fever with mecillinam.

In vitro studies carried out in this Department confirmed the high activity of mecillinam against Salmonella spp. As a result we set up a study to investigate the efficacy of mecillinam in patients suffering from enteric fever. To date 13 out of 15 patients with typhoid or paratyphoid fever have been successfully treated with this new amidinopenicillanic acid antibiotic.


In vitro studies with mecillinam on Escherichia coli and Pseudomonas aeruginosa.

The ability of a beta-lactam antibiotic to inhibit the growth of Gram-negative bacteria depends on three main properties: ting sites in the bacterial cell; the ability to penetrate through the outer layers of the bacterial envelope to these sites; and the ability to resist destruction by beta-lactamases that may be encountered on the way to the target. This article describes the properties of mecillinam with respect to the last two of these properties. Although able to hydrolyse mecillinam under some conditions, the beta-lactamases present in many Gram-negative species are unlikely to be very effective at protecting the bacteria in vivo because of their relatively low affinity for this penicillin and the good penetrative properties of the antibiotic.


Inhibition and facilitation of transfer among Pseudomonas aeruginos R plasmids.

Esamining 12 plasmids in Pseudomonas aeruginosa, we found two types of interaction in their transfer (inhibition and facilitation), using donor cells carrying two compatible plasmids. (i) Ten plasmids representing incompatibility groups P-1, P-2, P-5, P-6, and P-7 were all transmissible at a high frequency, 10-2 to 10-1, except for one with a lower frequency of about 10-3. The transfer of P-5 plasmids was inhibited by P-2 plasmids reciprocally or unilaterally, and the unilateral transfer inhibition was observed in other combinations between plasmids belonging to groups P-1, P-2, P-6, and P-7. It was characteristic of Pseudomonas plasmids that most plasmids with high transferability inhibited the transfer of other coexisting plasmids without distinct inhibition of their own transfer. (ii) Two plasmids, Rms149 of P-8 group and Rlb679, which was not classified, were transmissible at an exceptionally low frequency of 10-7 to 10-6, but their transfer was facilitated by plasmids with high transferability.