Induction of specific unresponsiveness against the C3H M1s=antigen in mice, increase of suppressive capacity of C3H X CBA F1-lymphocytes after sensitization against CBA lymphoid cells.

Injection of adult CBA mice with lymphocytes from C3H X CBA donors leads to a specific reduction of the MLC reactivity of the recipients' lymphocytes. This effect is mediated by a population of F1-lymphocytes which do not seem to possess the relevant MLC-stimulatory M1s-antigen. In this investigation we have shown that injection of C3H X CBA mice with CBA, but not C3H spleen cells enhances the 'tolerogenic' capacity of their thymocytes and lymph node cells. A similar enhancing effect was achieved by 'educating' C3H X CBA lymphocytes in irradiated CBA, but not C3H hosts. The results indicate that C3H X CBA lymphocytes reduce the MLC-reactivity by reacting immunologically against CBA T-cells which possess recognition structures for the relevant M1s antigen. Lymphocytes of C3H X CBA mice can be sensitized against such recognition structures which thus renders them more 'tolerogenic'.


A readout for pulsed Doppler velocity meters.

The use of the pulsed Doppler velocity meter in cardiovascular applications has been restricted, due in part to difficulties in experimental usage of the device and systematic errors in signal processing, leading to inaccurate results. These problems have been alleviated by a multiparameter readout which provides information on the position of the sample region with respect to surrounding tissues in an M-mode type display, and a first moment Doppler frequency shift output capable of following the rapid velocity fluctuations which occur in disturbed flow conditions. The use of the readout in obtaining blood velocity measurements from within the human heart is demonstrated with representative examples of output for various clinical situations.


[Penicillinase-producing Neisseria gonorrhoeae].

The present state of epidemiology and the microbiology of beta-lactamase-producing N. gonorrhoeae are reviewed. Methods of identification of such strains and therapeutic consequences are discussed.


[Vitamin B 12-(cyanocobalamin)-allergy].

A case of vitamin B12 allergy is reported. Typical eczematous and exanthematic skin lesions appeared after long-term and high-dosed intake of a vitamin B12 drug (Biovital). Patch tests with vitamin B12 were positive. This observation of vitamin B12 allergy we compared with previous published cases.


[Treatment of inflammatory and proliferative skin diseases].

Treatment of inflammatory and proliferation dermatoses can now be accomplished with pharmacologic agents which inhibit production of mediators or their actions. The immune system can be stimulated by thymosin, imidazo drugs, BCG, corynebacterium parvum and idoxyuridine. Immune complex diseases may be treated with corticosteroids, clofazimine, sulfonamides, antimalarial drugs, and nicotinic acid. Low dose, safe immunosuppressive therapy can successfully control scleromyxedema, guttate parapsoriasis, histiocytosis X, Kaposi's sarcoma, and Sézary syndrome.


In vivo incorporation of 3H-glycerol and 14C-palmitate into lipids of subcellular fractions of the myocardium hypertrophied during experimental hypoxia.

Incorporation of labelled precursors into neutral lipids and phospholipids of hypertrophied guinea-pig cardiac ventricles during normobaric hypoxia (breathing gas mixture of N2: O2, 9: 91%) was studied. The lipids of the heart were isotopically labelled in vivo with [1-14C] palmitate and [2-3H] glycerol, and, after a period of 2 hours, the incorporation of the two injected precursors into mitochondrial and microsomal fractions was determined. Eighty hours after the onset of the hypoxic treatment, the specific activities of isolated lipids showed a more elevated incorporation into lipid classes of hypoxic right and left ventricles with respect to that of the control. For both precursors, the percent increase of incorporation into microsomal and mitochondrial neutral lipids was higher than into phospholipids. In the microsomal fraction the increase of 14C-radioactivity incorporation was more pronounced than 3H-incorporation. 3H/14C incorporation ratio appeared decreased in hypoxic ventricles. The data in this experiment suggest that the net increase of 3H-glycerol and 14C-palmitate incorporation into myocardial lipid classes was a compensatory response of the heart to the hypoxic stimulus.


Ca2+ regulation in vascular smooth muscle.

Regulation of aorta smooth muscle contraction by Ca ion requires the collaboration of the 80,000 dalton factor and tropomyosin. A method for preparing pure actin from aorta smooth muscle is described.


Increased (Na+,K+)-ATPase concentrations in various tissues of rats caused by thyroid hormone treatment.

Effects of triiodothyronine treatment on (Na+,K+)-ATPase in the brain, liver, kidney, and skeletal muscle were studied in the rat. The number of (Na+,K+)-ATPase units in the particulate fractions obtained from deoxycholate-treated homogenates was estimated from the concentration of [3H]ouabain binding sites assayed with a labeled drug-displacement method. The concentration of [3H]ouabain binding sites was highest in the brain tissue, intermediate in the kidney, and relatively low in the liver and skeletal muscle. The affinity of the binding sites for ouabain was highest in the brain, intermediate in the skeletal muscle, low in the kidney, and lowest in the liver. Triiodothyronine treatment increased the [3H]ouabain binding site concentration in the liver, kidney, and skeletal muscle but failed to affect it in the brain. Affinity of the binding sites for ouabain was unchanged by the triiodothyronine treatment in all tissues studied. These data indicate that triiodothyronine treatment of rats results in an increased tissue concentration of (Na+,K+)-ATPase in the liver, kidney, and skeletal muscle, but not in the brain. These changes do not accompany marked changes in the characteristics of the enzyme.


Glycolysis of quiescent cultures of 3T3 cells. Addition of serum, epidermal growth factor, and insulin increases the activity of phosphofructokinase in a protein synthesis-independent manner.

Addition of serum to quiescent cultures of 3T3 cells markedly enhances the specific activity of phosphofructokinase assayed in centrifuged homogenates. The effect depends on both serum concentration and the time of exposure to serum. Mixing experiments, mearsurements of the enzyme at different pH values and persistence of the activation after Sephadex chromatography render unlikely the possibility that activators or inhibitors play a significant role in the stimulation of phosphofructokinase by serum. In addition to serum, epidermal growth factor and insulin also enhance the activity of phosphofructokinase. The activation occurs in the presence of 30 microgram/ml of cycloheximide. It is not the result of a high glycolytic flux because drugs (dinitrophenol and oligomycin) that interfere with ATP synthesis and are potent stimulators of glycolysis in intact cells fail to increase phosphofructokinase activity and because the growth-promoting factors increase the enzyme activity in glucose-free medium. Thus, the activation of phosphofructokinase activity appears specifically related to the action of growth-promoting factors and it may offer an experimental system to investigate the chemical signals or cellular conditions, or both, that lead to rapid cell proliferation.


Colicins and bacterial membranes: structures and functions. II. Studies on reconstituted homologous and hybrid membranes prepared from cytoplasmic membranes of untreated and colicin K-treated bacteria.

Cytoplasmic membranes of Escherichia coli K12 C600 treated and not treated with colicin K were dissociated into unsolubilized and solubilized fractions. Neither fraction catalyzed ATP-linked transhydrogenase activity. Mixtures of unsolubilized fractions of the untreated bacteria with solubilized fractions of either the treated or untreated bacteria yielded reconstituted membranes with restored ATP-linked transhydrogenase activity. The level of the activity was similar to that of the undissociated membranes of untreated bacteria. The membranes which were reconstituted from unsolubilized fractions of the treated bacteria and the solubilized fraction of the treated or the untreated bacteria showed impairment of activity. The impairment is not due to an inability to bind ATPase of the soluble fraction or to an incorrect binding of the ATPase. The impaired, reconstituted membranes showed striking decreases in the relative amounts of three proteins with apparent molecular weights of 122,000, 73,000, and 62,000. The affected proteins were found to be components of the unsolubilized membrane fraction. It is, thus, concluded that the impaired activity is due to the defective nature of the unsolubilized membrane fraction of colicin-treated cells.


Bile acid-induced increase in bile acid-independent flow and plasma membrane NaK-ATPase activity in rat liver.

Previous studies showed that in rats with obstruction of the bile ducts draining the median and left hepatic lobes, and in rats with normal bile ducts in which the bile acid pool size and secretion were augmented by 48-h intraduodenal infusion of taurocholate, bile acid flux through secreting hepatocytes was increased. Under these conditions, taurocholate transport maximum exhibited a time-dependent adaptation to increased secretory load.Unexpectedly, bile acid-independent canalicular flow in these experimental models also was found to be increased when measured at 48 h. Relative to controls, bile acid-independent flow per gram of nonobstructed liver was increased approximately threefold in selectively obstructed rats and 43% in bile acid-loaded rats with normal ducts. In rats infused with bile acids at similar rates for only 16 h, no increase was observed. Studies with [(14)C]erythritol suggested that the increased bile flow under these conditions was of canalicular origin.NaK-ATPase activity in canaliculi-enriched liver plasma membrane preparations from the nonobstructed lobes of selectively obstructed rats and from 48-h bile acid-loaded rats was increased by 47% and 52%, respectively, relative to controls, but was not increased in membranes from 16-h bile acid-loaded rats. Canalicular membrane 5'-nucleotidase and Mg ATPase also were increased. These studies show that augmented bile acid flux through secreting liver causes an adaptive increase in bile acid-"independent" flow and in the activity of canalicular membrane enzymes. The mechanism by which bile acids modulate this and previously reported aspects of bile secretion remains to be elucidated.


Cytotoxic activity of lymphocytes. VII. cellular origin of alpha-lymphotoxin.

To detect the cellular origins of alpha-lymphotoxin (alpha-LT), we cultured various subpopulations of human blood lymphocytes separated by erythrocyte-rosetting techniques with various mitogens. T cell-enriched subpopulations responded to PHA by increased 3H-thymidine uptake into DNA and large amounts of alpha-LT production. SPL and Con A-Sepharose stimulated DNA synthesis in T cell-enriched cultures if the macrophage content was greater than 1.5%; however, alpha-LT production was not induced by these two mitogens even when reconstituted with 10% macrophages. B and/or null cell-enriched populations severely depleted of T cells (less than 0.7% did not respond to PHA, SPL, or Con A-Sepharose. However, reconstitution to 5 or more percent in E-RFC allowed all three mitogens to stimulate DNA synthesis and alpha-LT production. The LT made by all cell populations 5 and 7 days after stimulation were equally neutralized by a heterologous antiserum to alpha-LT. These results show that human T and B and/or null cells, when appropriately stimulated, can produce alpha-LT.


Nature of the antigenic complex recognized by T lymphocytes. V. Genetic predisposition of independent F1 T cell subpopulations responsive to antigen-pulsed parental macrophages.

Nonimmune (2 x 13)F1 guinea pig T lymphocytes initially stimulated with trinitrophenyl- (TNP) modified macrophages from one parental strain and then treated with bromodeoxyuridrine (BUdR) and light are unable to be primed subsequently with TNP-modified macrophages of the same parental strain. In contrast, these BUdR and light treated F1 T cells can be primed with TNP-modified macrophages of the other parental strain. These results demonstrate that in a nonimmune F1 animal two T cell subpopulations exist before priming that are genetically predisposed to respond to antigen associated with macrophages derived from one or the other parent.


Topical bioavailability of a potential anti-acne agent (SC-23110) as determined by cumulative excretion and areas under plasma concentration time curves.

The topical bioavailability of a potential anti-acne agent ([14C]-SC-23110) was determined in the rhesus monkey, an animal model relevant to man. By the method of cumulative excretion in urine and feces the percutaneous absorption of 21 microgram/cm2 of the free base form was determined to be 0.58 +/- 0.16 (SD) percent of the applied dose. The mean areas under the plasma concentration time curves (AUC) following topical and intravenous administration were also determined. The ratior of the AUC's following topical and iv administration gave a bioavailability of 0.49% of the applied dose, a value in good agreement with the 0.58% obtained by cumulative excretion. Plasma AUC curves can be used to determined the percutaneous absorption (bioavailability) of compounds. Percutaneous absorption of [14C]-SC-23110 (80 microgram/cm2) when topically applied as the salt or free base form was compared. Twice the amount of compound was absorbed as the free base (0.34%) than as the salt (0.17%).


Chronic atrial fibrillation and coronary artery disease.

Retrospective study of the incidence of atrial fibrillation (AF) in 841 consecutive patients who had selective coronary arteriography and left ventricular catheterization from January 1, 1966 to December 31, 1976 was undertaken. There were 496 patients with coronary artery disease (CAD), 138 with valvular disease or cardiomyopathy, and 207 were normal. Chronic atrial fibrillation was present in 45 patients, of whom 35 has valvular disease or cardiomyopathy. One had coronary artery disease and 9 were normal. Chronic atrial fibrillation in coronary artery disease was rarely found.


Transduction of penicillinase production and other antibiotic-resistance markers in Staphylococcus epidermidis.

Transduction of resistance from a multiply antibiotic-resistant strain of Staphylococcus epidermidis sub-group II was studied using the typing phage 108. The effect of increasing doses of ultraviolet radiation on the transducing phage was used to indicate the chromosomal or plasmid nature of the genes. Tetracycline and chloramphenicol resistance behaved as plasmid genes and streptomycin resistance as a chromosomal marker. It was also possible to transduce penicillin resistance (Pc) due to penicillinase production (bla+) using a low level of benzylpenicillin (0.03 microgram ml-1) for recovery. Approximately 10(-5) transductant colonies per phage input were obtained and ultraviolet kinetics indicated that Pc was plasmid carried. Pc transductants fell into two categories. In one group PC was stable as in the donor strain and transductants had the same phage sensitivity as the recipient. In the other, Pc was unstable at 37 degrees C and the instability was enhanced by growth at approximately 43.5 degrees C; these transductants also gained genes for restriction and modification of certain phages. Transductants that subsequently lost bla+ also lost the restriction and modification characters.


Tumours of the cauda equina.

A retrospective study of 70 consecutive patients with a cauda equina tumour who were admitted to Neurosurgical Department at the Radcliffe Infirmary, Oxford is presented. The diagnosis of these tumours is often difficult and delayed. The quality of life largely depends upon the neurological disability at presentation. The diagnostic features and investigations are discussed together with the treatment and prognosis.


Small-signal analysis of response of mammalian muscle spindles with fusimotor stimulation and a comparison with large-signal responses.

1. Response dynamics of primary and secondary muscle spindle endings to small-amplitude sinusoidal stretches were found to be unaltered by tonic repetitive stimulation of fusistatic or fusidynamic fibers. 2. Overall sensitivity of these receptors is decreased by fusistatic stimulation and either unchanged, increased, or decreased by fusidynamic stimulation at rates of 75/s or greater. 3. In the case of primary endings, the results obtained with small-amplitude sinusoidal stretches are not compatible with the response of these receptors to large-amplitude ramp stretches. The difference is explained by dependence of receptor dynamics on stretch amplitude. Fusistatic stimulation tends to prevent those changes in dynamics, whereas fusidynamic stimulation tends to enhance them. 4. In the case of secondary endings, the results obtained with small- and large-amplitude stretches appear to be compatible with a linear model for this receptor (i.e., one with dynamics independent of input parameters). 5. By modulating the frequency of stimulation applied to fusimotor fibers and comparing the resulting afferent response to the receptor response to stretch dynamic characteristics of intrafusal muscle contraction can be deduced. The results suggest that the dynamics of fusiastatic and fusidynamic contraction are the same and, furthermore, that they are the same as those of extrafusal muscle. We note that the result is incompatible with measurements of the time course of twitch and tetanus development and suggest, therefore, that muscle dynamics are a function of contractile state.


Localization of sodium pump sites in cat salivary glands.

1. Cat submandibular glands were perfused with Locke solution containing [3H]ouabain. In some experiments additional medium was given by retrograde intraductal injection. 2. [3H]ouabain binding sites were localized by light microscopical autoradiography and the findings compared with the electron micrographs. 3. The cells of the striated ducts were heavily labelled with [3H]ouabain, predominantly in the contraluminal parts. 4. At the acinar level moderate amounts of [3H]ouabain were found in relation to the plasma membranes of the demilunar cells. The central acinar cells were found to be virtually devoid of [3H]ouabain. 5. Electron microscopy revealed that the demilunar cells possessed long, tortuous intercellular spaces separated from the secretory canaliculi by junctional complexes. In contrast, the membranes between adjacent central acinar cells were fairly straight. 6. It is concluded that the striated ducts play a dominant role in the ductal reabsorption of sodium, and that the transport is probably mediated by a (Na+ + K+)-activated ATPase. The findings on the acinar level are in agreement with the view that the primary saliva is formed predominantly by the demilunar cells. The role of a (Na+ + K+)-activated ATPase in this process is unclear.


Removing a sewing needle from the pelvic cul-de-sac with an operative laparoscope.

A case is reported of an unusual foreign body, a sewing needle, found in the pelvis beneath the peritoneum of the cul-de-sac and its successful removal via laparoscopy. The preoperative radiologic localization techniques are discussed. The use of the laparoscope for removing accessible foreign bodies can obviate the need for a more extensive surgical procedure.


Electrogenesis from an ATPase-ATP-sodium pseudo pump.

The short circuit current and the open circuit voltage responses of membranes to ATP, which have been attributed to membrane ATPase acting as a sodium pump, have been reproduced not only in a lipid membrane containing solubilized ATPase but also in membranes formed of the phospholipids contained in ATPase. The response is greatest with cardiolipin, but occurs with other acidic phospholipids. This observation of electrogenesis without hydrolysis is a surface phenomenon probably due to the alignment of ATP on the phospholipid by ion association at its interface with the water phase. The finding constitutes a precaution for interpreting studies of membrane Na-K-ATPase or for its incorporation into an artificial membrane. The substances necessary for electrogenesis are present at the mitochondrial membrane, and the particular orientation of the ATP on the phospholipids in vitro suggests a role for this ion association in the function of Na-K-ATPase.


Effect of thymosin on T-lymphocyte functions in patients with acute thermal burns.

Patients with severe thermal burns demonstrate a decreased cellular immunity. The purpose of this study was to ascertain whether thymosin enhances in vitro T-lymphocyte functions in such patients. Peripheral blood lymphocytes were obtained serially from 22 burned patients and 35 health adults. In vitro lymphocyte functions were evaluated by E-rosette formation, lymphocyte culture responses to PHA, Con A, PWM, PPD, SK-SD, mumps antigen, and tetanus toxoid, and mixed lymphocyte culture reactions. These tests were performed with and without in vitro addition of thymosin. Most of the parameters examined were significantly decreased in patients during the first 2 weeks postburn. The in vitro addition of thymosin significantly restored impaired lymphocyte responses, except in mixed lymphocyte culture reactions. These results demonstrate that thymosin enhances certain in vitro T-lymphocyte functions in burned patients. They further suggest that the administration of thymosin may restore decreased cell-mediated immunity in severely burned patients.


Complications of diagnostic paracentesis in patients with liver disease.

A retrospective analysis of 242 consecutive diagnostic abdominal paracenteses in patients with liver disease disclosed seven major complications, including serious hemorrhage (four), perforation of bowel with generalized peritonitis (one), perforation of bowel with abdominal wall abscess (one), and a catheter fragment left in the abdominal wall or cavity (one). The results of this study emphasize the potential dangers of this procedure in these patients and raise the possibility that complications may be more common than previously thought.


Determination of right ventricular wall thickness by echocardiogram.

Right ventricular wall-thickness measurements were performed by echocardiography and at necropsy in 25 patients. Correlations were made and found to be good in all subjects (r = .82). The echocardiographic technique was successful in separating nine patients with right ventricular hypertrophy from 16 patients without right ventricular hypertrophy at necropsy. The diagnosis of right ventricular hypertrophy by ECG correlated poorly with necropsy and echocardiographic findings. Right ventricular wall thickness can be accurately measured by echocardiography.


The treatment of gonococcal proctitis. An evaluation of 173 patients treated with 4 g of spectinomycin.

A group of 1,533 homosexual males were examined in 1976 for gonorrhea at the Skin Clinic of the Boston Dispensary. This examination included a rectal culture. There were 213 males with positive rectal cultures: an infection rate of 13.7%. Of these, 173 were treated with 4 g of spectinomycin hydrochloride, intramuscularly, and 127 (73.4%) returned in one week for a posttreatment examination and culture. All who returned had a negative culture. Four grams of intramuscular spectinomycin hydrochloride appears to be effective in the treatment of gonococcal proctitis.


[Echocardiography in evaluation of the results of surgical treatment of aortic coarctation].

Patients with isolated coarctation of the aorta were examined by echocardiography be fore operation and in the immediate and remote postoperative period. Before operation all the patients had marked hypertrophy of the myocardium of the left ventricle displayed by an  increase in its thickness during the diastole and by an increase in its mass. Besides myocardial hypertrophy, most patients had dilatation of the left ventricle. In the immediate postoperative period a decrease in the dilatation of the left ventricle was noted in patients of the younger age group. The mass of the myocardium did not change in most patients. In the remote postoperative periods a decrease in the mass of the myocardium of the left ventricle was revealed, which was most marked in adult patients.


[Ischemic heart disease in a group of men 35 to 44 engaged in stressful mental work (data from the 1st examination)].

A group of 514 males between the ages of 35 and 44, whose occupation involved strained mental work, were examined. Ischemic heart disease was diagnosed in 56 of them (10.7%); 191 formed a group with doubtful signs of ischemic heart disease, and 267 composed a group of practically healthy persons. Hypertensive disease was revealed in 18.4% and hyperlipoproteinemia in 20% of persons examined. There was a statistically significant difference between the group of healthy individuals and that of patients with ischemic heart disease in the frequency of hypertensive disease and hyperlipoproteinemia. Smoking, adiposity, low physical activity, and aggravated heredity were encountered at a practically equal rate in both groups. In half of the patients with ischemic heart disease hypertensive disease and hyperlipoproteinemia were not found, while other risk factors of ischemic heart disease were encountered no more frequently than in the group of healthy persons. Thus, just like most other epidemiologic studies, our investigation showed hypertensive disease and hyperlipoproteinemia to be of highest significance as ischemic heart disease risk factor.


[Alcoholic heart disease (alcoholic cardiomyopathy)].

With no intention of belittling the importance of chronic ischemic heart disease (CIHD) in modern cardiology, the article focuses the attention on primary alcoholic heart disease--alcoholic cardiomyopathy (ACMP)--which arouses a far from causal interest due to the prevalence of alcoholism. It is suggested to distinguish three main clinical forms of ACMP: valence of alcoholism. It is suggested to distinguish three main clinical forms of ACMP: (1) "classical", manifested by dilatation of the heart and signs of its failure; (2) "quasi-ischemic" manifested by cardialgia and changes in the ECG, resembling those in CIHD; (3) "arrythmic", characterized by variants of disorders of myocardial excitability and conduction. The ACMP diagnostic criteria, methods for its identification and differential diagnosis from CIHD, modern conceptions of ACMP pathogenesis, and the main principles of treatment are discussed.


[Diagnostic problems in mosaic-Downs-syndrome (author's transl)].

In 14 cytogenetically diagnosed patients with mosaic Down's syndrome a dermatoglyphic examination was performed. A highly significant correlation between the percentage of trisomic cells and the grade of mongoloid stigmata in the dermatoglyphic pattern was observed. In 11 of the 14 patients a second chromosome analysis could be done after different periods. In several cases a very distinct shifting between the normal and the trisomic cell line occurred. In three patients the normal cell line disappeared and in one other patient the trisomic cell line was lost. The diagnostic problems are pointed out which occur by the total loss of trisomic cell lines. The value of dermatoglyphic examinations in such cases is discussed.


Humoral inhibitors of the immune response in uremia. I. Effect of serum and of the supernatant of spleen cultures from uremic rats on the mixed lymphocyte reaction.

The effects of the serum of rats with experimentally induced chronic renal failure and of the supernatant of cultured spleen cells obtained from these animals were tested in the mixed lymphocyte reaction (MLR). Serum of uremic rats with blood urea nitrogen levels greater than 35 mg. per 100 ml. and supernatant of spleen cultures from animals with blood urea nitrogen levels greater than 60 mg. per 100 ml. were found to be inhibitory to the MLR. The inhibitory activity of uremic serum was directly correlated with blood urea nitrogen levels. The inhibitory activities both of uremic serum and of the supernatant of cultured uremic spleen cells were further studied and compared. Dialysis in vitro does not remove the suppressing effect of serum or of supernatant on the MLR. Irreversible inhibition of the MLR is observed after 48 hours' exposure to the serum or to the supernatant; this inhibition occurs whether the MLR culture is exposed during the first 48 hours or last 48 hours of incubation. In some uremic rats the inhibitory activity of the serum disappears or is weakened after splenectomy, despite a continued rise in blood urea nitrogen levels.


Effect of 5-bromodeoxyuridine on deoxyribonucleic acid-protein adducts induced by ultraviolet light on chromatin cells.

The formation of DNA-protein adducts induced by ultraviolet irradiation (254-nm. wavelength) has been analyzed by cesium chloride equilibrium sedimentation. The formation of ultraviolet-induced DNA-protein adducts is increased in 5-bromodeoxyuridine-substituted chromatin. Cross-linking is dependent in part upon the extent of 5-bromodeoxyuridine substitution, and is detectable either in chromatin irradiated in vitro or in chromatin from cells irradiated in vivo prior to the isolation of chromatin. As much as 80% of the DNA can be cross-linked to proteins by ultraviolet irradiation of 5-bromodeoxyuridine-substituted chromatin at a fluence of 2,928 Jm-2. In unsubstituted chromatin 11,712 Jm-2 are required to obtain to obtain the same effect. Under the same conditions of 5-bromodeoxyuridine replacement and ultraviolet irradiation only 10% of the total chromosomal proteins can be cross-linked to DNA, whether in vivo or in vitro. Approximately two-thirds of the cross-linked proteins chromatograph as nonhistone proteins, the remaining one-third as histones.


[Course of intraluminal esophageal pressure after laryngectomy (author's transl)].

A new electronic equipment permits the measurement of the course of intraluminal esophageal pressures in patients before and after laryngectomy. The values obtained in all parts of the esophagus could be reproduced, thus proving the correctness of the measuring system. In patients with laryngectomy having a good compensatory esophageal voice the pressures in the lower esophageal sphincter doubled, when compared with those patients with laryngectomy which had little or no compensatory voice. The pressure in the area of the upper esophageal sphincter was reduced because of the laryngectomy, and the pressure in the area of the upper third of the esophagus was unchanged. There was no difference between the groups with good and with poor esophageal voice.


[Otorhinolaryngological-neurosurgical problems on the skull base (author's transl)].

Adequate tumour surgery on the skull base is, because of the close connection with vital blood vessels and nerve structures, difficult and full of risks. From six rare cases, an account is given here, of experiences which were gained by the combined ENT and neurosurgical team work. Singularly, the approach to processes of the frontal, middle and hind skull base is discussed. Through diagnosis, and when indicated, combined operative team work between the Otolaryngologist and the Neurosurgeon, using microsurgical operative techniques, reorganizational advancements regarding the maintenance of function and functional reconstruction, in the surgery of the base of skull, are possible. Under this aspect, endeavors must be made in this area, by slow growing benign new growths, to establish an early diagnosis, and the earliest possible operation, thus promoting the chances of preservation of the remaining undamaged blood vessels and nerve structures.


[Vagus neurinoma of the basic of the skull and endocranium (author's transl)].

We are discussing a case of neurinoma of the tenth cranial nerve in the area of the base of the skull with endocranial extension in a 51-years-old female patients. The first symptom was hoarseness of the voice, and three years later more cranialnerves were involved (V-VII-X-XI-XII). The existence and the extension of the tumor was verified by radiological examination of the base of the skull, carotic angiography, myelography and scanning; the diagnosis was proved by biopsy. The treatment of choice is the operation because the tumor is radioresistant.


[CSF-rhinorrhea due to removal of an acoustic neuroma (author's transl)].

After removal of an acoustic neuroma by the suboccipital route cerebrospinal fluid rhinorrhea was observed. This procedure was complicated by meningitis and pneumatocephalus. Finally, after one neurosurgical and four otosurgical interventions, the cerebrospinal fluid leak was identified in the membrane of the round window. It was plugged with a fascial graft.


[The trigeminus nerve in neuro-otological diagnosis (author's transl)].

The Trigeminus nerve is represented by a large area in brainstem and therefore we often find symptoms of this nerve, if there are dysfunctions in this region. Especially when we suspect disorders of the central part of the vestibular or auditory systems the Trigeminus can give distinct signs. Besides other qualities (tactile, nociceptive) the sensitivity for warmth can be measured exactly with the thermic-impulse-test (TITT). The importance of this test is shown in some cases (tumor of the cerebello-pontine angle, tumors in the brainstem and multiple sclerosis). On the other hand in lesons of the facial part of the skull (traumatic, tumoral and postoperative) the TITT gives reliable signs and seems to be more sensitive than other tests of Trigeminus.


[For the documentation of the results of the positional test a new schematic pointer diagram is recommended, the positiogram (author's transl)].

It contains six fields representing the six main positions of the test. In each field the intensity and the duration of the positional nystagmus are given by the coordinates of the maximal frequency as abscissa and of the duration as ordinate. The direction of the nystagmus is arrowed by the direction of the resulting pointer. The survey on all the six fields informs about the pertaining nystagmus direction, its intensity and positional type. The positiogram enhances a quick evaluation of the positional test and facilitates follow-up studies.


[Clinical comparison of perrotatory and postrotatory nystagmus characteristics (author's transl)].

Rotatory stimulation is a physiological stimulation of the vestibular canalicular organs. In every day's neurootological routine it is applied in sinusoidal, triangular and trapezoidal shape. The rotatory intensity damping test (RIDT) applies a perrotatory and postrotatory test combination of a trapezoidal stimulus pattern. Thus the perrotatory as well as the postrotatory nystagmus can be recorded during several phases of the after phenomena. In terms of acceleration/time plots the supraliminal perrotatory acceleration exhibits a rectangular or step-like stimulus characteristic. The supramaximal postrotatory stimulus however has a needle-like impulse pattern. The nystagmus reaction being recorded by the ENG is evaluated according to frequency or beat-rate distributions. The perrotatory nystagmus can be linearily optimalized in a linear to linear plot during its maximal reactional dynamics. The postrotatory nystagmus distribution can also be linearily graphed in a nomogram. However this nomogram is a log.log intensity/time-chart. This paper clinically compares per- and postrotatory reactions of the rotatory intensity damping test. It can be seen that this test adds important information to the clinical study of the dizzy patient.


[The intratracheal behavior of the ear-composite graft. An experimental and histological study (author's transl)].

The behavior of the composite graft obtained from the concha of the external ear is studied in mini-pigs, 25, 35, 46 and 85 days following transplantation into the tracheal wall by light- and electromicroscopy. The squameous cell epithelium persists to the same extent, but its thickness has decreased as well as desquamation by adaption to the intratracheal conditions. The transplanted cartilage started degeneration in the 4th postoperative week by a slowly and continous transformation into a granulating and fibrous tissue. The adjacent respiratory epithelium reacts by hypersecretion and by the increase of goblet cells. Therefore it may be differentiated from the transplanted squameous cell epithelium. The suture material vicryl is well tolerated causing only a slight reaction by the surrounding tissue, so far as the stitch is placed intraluminally through both, the transplant and the tracheal wall.


[Ultrastructure of hemidesmosomes in invasive laryngeal carcinoma (author's transl)].

The occurence, distribution, and ultrastructural morphological of hemidesmosomes in malignant epithelial cells of invasive squamous cell carcinoma of human larynx were studied by electron microscopy. In the more advanced invasive carcinomas, the hemidesmosomes were reduced in number or were absent as was the basement membrane over extensive areas of the epithelial-connective tissue junction. In other places structural alterations of the hemidesmosomes were seen as a defective attachment plaque on the cytoplasmic side of the internal leaflet of the plasmalemma including retraction or absence of the inserting tonofilaments. Other structural changes were found to involve the basement membrane and the associated subbasal fibrous elements of the epithelial-stromal junction. Hemidesmosome-containing areas of the basal plasma membrane were seen to invaginate and to appear to pinch off. It was observed that the detached hemidesmosomes rounded up with their cytoplasmic attachment plaque lying on the inner circumference of the vesicular structures. These vesicular hemidesmosomes contained components of their extracellular portion. The observations indicate that autophagocytosis of detached hemidesomosomes may lead to the reduction of epithelial-dermal adherence and may thus facilitate the invasion of the underlying stroma by invasive carcinomas of the larynx.


[Problems of early diagnosis of carcinoma of the cancer of the larynx (author's transl)].

Using the anamneses of 1231 patients with laryngeal carcinoma, who were treated in the ORL-clinic at the University om Halle, we investigated the relations among the duration of the anamneses, the place and the stage (TNM-system) of the tumor at the first registration. The causes of the neglection by the patient, the family doctor and the medical specialist are pointed at, and the possibilities for a modern laryngological diagnosis are given. An improvement of the early registration of patients with laryngeal carcinoma cannot be proved in the area of this clinic during the period from 1940 to 1974.


[Statistics on 1231 patients with cancer of the larynx 1940 to 1974 (author's transl)].

At the ENT-Univ. Clinic Halle/Saale 1231 patients suffering from an histological verified cancer of the larynx have been observed over the last 33 years. The numbers of male cases have been trebled within the last 30 years. This trend could not be observed in women. The increase is connected with a remarcable concentration of the supraglottic localisation. Despite of intensive information of the population most of the patients only turn to our clinic in the stage II and III (TNM-system). Only in 9.9% of the cases their fate remained unknown.


[Amyloidtumor of the larynx (author's transl)].

Report on two cases of local amyloid-tumors of the larynx. The microsurgical resection resulted in excellent functional recovery. One year after surgery no signs of recurrency were observed.


[Specialities of female patients with laryngeal carcinoma (author's transl)].

Among 1231 patients with laryngeal carcinoma were 48 women. These were compared with male patients showing laryngeal carcinoma with respect to nine various groups of criteria. There was no significant difference in: Histological Diagnosis, the first symptom, the second tumor. In opposition to male patients with laryngeal carcinoma the number of women's carcinoma has not increased since 1940. Women are relatively more frequently taken ill at a younger age, they show a longer anamnese and relatively more frequently suffer from an inner carcinoma than men. Although the female patients with laryngeal carcinoma were attended relatively frequently at a rather favourable stage, we were not able to notice any better results after the five years' survival in comparison with the male patients.


Photography as a method of recording and improving skill in laparoscopy.

The techniques of photography in diagnostic laparoscopy are presented. It is suggested that photography, as well as being the best method of recording information, is of great use in improving and teaching laparoscopic skill, through comparison of case findings either at subsequent laparotomy on the same patient, or in similar conditions found at laparoscopy in different patients. Presumptive and hurried diagnoses cannot be made if a camera is used; the abnormality must be found to be photographed and recorded. A plea is made for the increased use of photography. Experience is presented with both polaroid and reflex 35 mm cameras.


Counselling about Down's syndrome: the parents' viewpoint.

The parents of 50 children with Down's syndrome were interviewed to find what sort of information they were given at the time of diagnosis and what arrangements were made for the child's future. Particular emphasis was placed upon the method and timing of giving the parents the diagnosis, the utilization of community resources to help the family and what information they would have liked to have been given in retrospect. The ages of the children ranged between three months and eight years at the time of the survey. Seventy-two per cent of parents were given the diagnosis during the first week, with an increasing proportion being dissatisfied with the timing the longer the delay in telling what was wrong with the child. The mother has been told first in 48% of cases, and both parents have been told together in only 20% of cases. Fifty-four per cent of parents were encouraged to take the baby home, 22% were encouraged to place the baby in an institution, while in 28% of cases the decision was left to them. Forty-six per cent of patients felt that an overly-pessimistic outlook had been given by the doctor. Eighty-four per cent had medical follow-up, community follow-up, or literature supplied, whereas 16% had no such arrangements made. The parents' own suggestions for better management were sought. The two most outstanding were to be placed in early contact with community facilities and to be given a chance to meet other parents of children with Down's syndrome.


[Vascular surgery in arterial occlusive disease. Possibilities and indications (author's transl)].

Besides amputation and resection of the sympathetic trunk, vascular reconstructive operations are among the most important surgical possibilities for the treatment of arterial occlusive disease. Disobliteration and bypass procedures come into consideration. Depending on the localization of the obstruction and the affected organ, one or the other method will be given preference. The indication for vascular reconstruction is principally governed by the disease complex, the danger to the organ due to the reduced blood supply and finally the extent of the arterial obstruction. The lethality of the intervention, the results, complications and follow-up are discussed in detail.


Circulating immune complexes in the idiopathic interstitial pneumonias.

We determined circulating immune complex levels and their correlation with pulmonary histopathology, immunofluorescence and steroid responsiveness in 24 patients with idiopathic interstitial pneumonias. Levels were elevated in all but three of 16 patients with cellular disease, but in none of eight with diffuse fibrosis (P less than 0.001). Granular deposition of IgG, usually with elevated levels, but in only 11 per cent of those with normal levels (P less than 0.001). The radiographic and physiologic response to corticosteroid therapy was better in patients with initially elevated levels than in those with normal levels (P less than 0.03). Circulating immune complexex are present in patients with cellular idiopathic interstitial pneumonias, have a pathogentic role in this disease and may identify a patient population that is potentially steroid responsive.


Raphe induced inhibition of intralaminar thalamic unitary activities and its blockade by para-chlorophenylalanine in cats.

Extracellular recordings were made of intralaminar thalamic neurones responding to stimulation of the radial nerves. The effects on this response of a conditioning stimulation of the median raphe nucleus were studied in both untreated and p-CPA pretreated cats. Ninety-two percent of thalamic responses to somatic stimulation in untreated cats was inhibited by conditioning stimulation of the raphe nucleus. The intensities of conditioning stimulation required for the inhibition were significantly higher in cats pretreated with p-CPA than in cats not treated with the drug. It is suggested that raphe projection to intralaminar thalamus excerts an inhibitory influence on thalamic activities, and that the inhibition is mediated by a putative neurotransmitter, serotonin. The possible involvement of the median raphe nucleus in pain processing is discussed.


[Telangiectasias].

Teleangectasia is of interest to the general practitioner, though rather ignored by pathologists and hence not easily dealt with as an organic whole. The clinical pictures of congnita and acquired (idiopathic and symptomatic forms) are explained. Treatments indicated for different forms include: surgical diathermy, injection of sclerosing substances, cryotherapy and the CO2 laser.


HBsAg and anti-HBs in staff and patients of a psychopaedic hospital.

One hundred and thirty-eight patients and 248 staff of Templeton Hospital and Training School were examined for hepatitis B surface ant,gen (HBsAg) and antibody (anti-Hbs) during a 14 month period. Sixty percent of the patients showed either HBsAg or anti-HBs. Twelve of 38 Down's syndrome and 10 of 100 intellectually handicapped patients were identified as asymptomatic carriers of HBsAg. Patients from 12 of the 19 residential units were sampled and some patients from all the units sampled had either HBsAg or anti-HBs. Twenty-five staff had detectable anti-HBs. Seventeen of these were psychopaedic nurses, employed in a psychopaedic hospital between three and 39 years (average 11.4 years). Only six of the nurses with anti-HBs had a pase history of hepatitis.


Iris tissue reaction to intraocular materials: feasibility for intraocular lens fixation.

We evaluated six commercially available materials for possible use in intraocular lens fixation. Dacron, Teflon, Marlex, nylon, silk, and catgut samples were placed adjacent to rabbit iris tissue and judged for tissue ingrowth and adhesion. Dacon produced maximal adhesion with minimal postoperative inflammation.


Factors of the langugage of pain in patient and volunteer groups.

An empirical determination of the nature and minimum number of dimension necessary to describe responses to the McGill Pain Questionnaire, and a comparison of groups, experiencing clinical or experimentally induced pain, on the dimensions were carried out. Eighty-five patients referred to a low back pain diagnostic clinic and groups of 129 volunteer students exposed to electric shock to pain threshold and pain tolerance levels described their pain using the McGill Pain Questionnaire's descriptive words. An incomplete principle component factor analysis of subjects' ratings suggested that 5 factors should be retained. These factors were judged to reflect: (I) immediated anxiety, (II) perception of harm, (III) somesthetic pressure, (IV) cutaneous sensitivity, and (V) sensory information. Canonical Analysis of Variance and univariate comparisons of back pain, threshold, and tolerance groups on these dimensions were conducted and implications for clinical and laboratory research discussed.


[Autumn ecology of Culicoides riethi (Ceratopogonidae) in the Kalmyk ASSR].

The activity of imago, habitats of preimaginal stages, intensity of the autumn hatching of imago and the initial period of their hibernation were investigated in summer-autumn of 1975 in the Kalmyk ASSR. The activity of winged insects in September was rather high, decreased in mid-October and ceased virtually by the beginning of November. The pupation and emergence of midges take place up to the second decade of October. IIId and IVth -instar larvae hibernate.


Aortic dystrophy: a cause of hypertrophic cardiomyopathy of obscure origin.

Cardiac hypertrophy of obscure origin, with or without features of congestive heart failure, is a relatively common finding at autopsy. A primary abnormality of cardiac muscle has usually been considered the basis of this condition. This paper proposes that the basic pathologic process does not affect the myocardium, but rather the ascending aorta. This "aortic dystrophy" is characterized grossly by diffuse ectasia of the ascending aorta, and microscopically by typical histologic features. The hypertrophy of the left heart appears to be work hypertrophy secondary to increased volume of the ascending aorta and reduced elastic recoil of the aortic wall following ventricular systole. The disorder in "idopathic" cardiac hypertrophy with aortic dystrophy is heritable (mendelian dominant), also affects the skeleton, and can be demonstrated in relatives. Dissecting aneurysm of the aorta is an alternative manifestation of aortic dystrophy, and may occur in families or in patients with "idiopathic" cardiac hypertrophy.


Further studies on the adaptation of fish myofibrillar ATPases to different cell temperatures.

Previous studies on fish Mg2+Ca2+ activated myofibrillar ATPases have been extended to species inhabiting diverse thermal environments. Cold adapted ATPases have considerably higher catalytic centred activities at low temperatures than warm adapted ATPases. Differences in cell temperature have also lead to evolutionary modifications in thermodynamic activation parameters. The free energies (deltaG2+), enthalpies (deltaH2+) and entropies (deltaS2+) of activation of the Mg2+Ca2+ myofibrillar ATPase are positively correlated with adaptation temperature. Myofibrils with CaATP-2 as substrate in the absence of Mg2+ will hydrolyse ATP by a mechanism not associated with fibril shortening. Differences in activation enthalpies (deltaHH) between cold and warm adapted Ca2+-activated myofibrillar ATPases are less pronounced than for the physiological ATPase. Furthermore the Ca2+-activated ATPase showed no relationship between environmental temperature and substrate turnover number or free energy of activation (deltaG2+).


[Diagnosis of a fibrosarcoma of the psoas presenting with fever only by gallium citrate scintigraphy (author's transl)].

A fibrosarcoma of the psoas in a 62-year-old woman manifested itself essentially by a febrile syndrome for approximately one year. It would appear that the first manifestation of the lesion occurred three years previously (lumbar pain). Careful clinical examination, numerous radiological studies and two exploratory laparotomies failed to reveal the site of the lesion. The latter was finally demonstrated by GaC67 gammagraphy. This case thus confirms the great value of this radioactive tracer in the diagnostic study of a febrile syndrome as a tumour syndrome. It would appear to be perhaps desirable, in this pathological context, to request a whole body study using GaC67 before proceeding to exploratory laparotomy.


Nucleotide sequence of Neurospora crassa cytoplasmic initiator tRNA.

Initiator methionine tRNA from the cytoplasm of Neurospora crassa has been purified and sequenced. The sequence is: pAGCUGCAUm1GGCGCAGCGGAAGCGCM22GCY*GGGCUCAUt6AACCCGGAGm7GU (or D) - CACUCGAUCGm1AAACGAG*UUGCAGCUACCAOH. Similar to initiator tRNAs from the cytoplasm of other eukaryotes, this tRNA also contains the sequence -AUCG- instead of the usual -TphiCG (or A)- found in loop IV of other tRNAs. The sequence of the N. crassa cytoplasmic initiator tRNA is quite different from that of the corresponding mitochondrial initiator tRNA. Comparison of the sequence of N. crassa cytoplasmic initiator tRNA to those of yeast, wheat germ and vertebrate cytoplasmic initiator tRNA indicates that the sequences of the two fungal tRNAs are no more similar to each other than they are to those of other initiator tRNAs.


Chemical evidence that proteolytic cleavage causes the heterogeneity present in human ceruloplasmin preparations.

Nine samples of human ceruloplasmin [iron(II):oxygen oxidoreductase; EC 1.16.3.1] prepared by different procedures have been examined for heterogeneity; gel electrophoresis showed that seven contained a number of components with molecular weights ranging from 20,000 to 130,000, and two contained largely a single component of molecular weight 130,000. Digestion of a single-component preparation with plasmin produced fragments with molecular weights similar to those found in the multicomponent preparations. Amino-terminal analysis, peptide mapping, and amino acid analysis showed that plasmin digestion generated a fragment of 20,000 molecular weight, which corresponded to a component present in a multicomponent ceruloplasmin preparation. The 20,000 molecular weight fragment appears to correspond to the so-called alpha-subunit or L-chain of human ceruloplasmin. Chemical evidence is thus provided that ceruloplasmin is a single-chain protein and that the so-called subunits are fragments. The 20,000 molecular weight fragment contains a single cysteine; amino acid sequence studies have shown that the sequence in the vicinity of this residue is similar to that around the single cysteine residue in plant plastocyanins and bacterial azurins, which are small, blue, copper-containing proteins.


Molybdenum cofactors from molybdoenzymes and in vitro reconstitution of nitrogenase and nitrate reductase.

A molybdenum cofactor (Mo-co) from xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) can be isolated from the enzyme by a technique that has been used to isolate an iron-molybdenum cofactor (FeMo-co) from component I of nitrogenase. N-Methylformamide is used for the extraction of these molybdenum cofactors. Mo-co from xanthine oxidase activates nitrate reductase (NADPH:nitrate oxidoreductase, EC 1.6.6.2) in an extract from Neurospora crassa mutant strain Nit-1; however, FeMo-co is unable to activate nitrate reductase in strain Nit-1. Mo-co from xanthine oxidase is unable to activate nitrogenase in an extract of Azotobacter vinelandii mutant strain UW45. Inactive component I in this extract can be activated by FeMo-co. These results indicate that nitrate reductase and xanthine oxidase share a common molybdenum cofactor, but this cofactor is different from the molybdenum cofactor in nitrogenase.A. vinelandii synthesizes both Mo-co and FeMo-co. Mo-co is produced when the cells fix N(2) and also when they are repressed for nitrogenase synthesis by growth in a medium containing excess ammonium. However, FeMo-co is not produced when cells are grown in an ammonium-containing medium. Partially purified preparations of component I from A. vinelandii and Klebsiella pneumoniae contain both FeMo-co and Mo-co. The presence of both FeMo-co and Mo-co activities in partially purified preparations of component I explains previous reports of activation of inactive nitrate reductase in strain Nit-1 by acid-treated component I of nitrogenase. The Mo-co can be separated from FeMo-co in these preparations by chromatography on Sephadex G-100 in N-methylformamide. Both FeMo-co and Mo-co are sensitive to oxygen.


31P nuclear magnetic resonance measurements of ATPase kinetics in aerobic Escherichia coli cells.

We have measured the in vivo unidirectional rates between the terminal phosphate of ATP and intracellular inorganic phosphate (PiIN) in aerobic suspensions of Escherichia coli cells using 31P nuclear magnetic resonance saturation transfer techniques. Typically, the measurements consisted of saturating the ATPgamma resonance and observing a 20 +/- 5% reduction in the intensity of the PiIN resonance. No saturation transfer was observed after incubation with 1 mM dicyclohexylcarbodiimide, an ATPase inhibitor. From the measured decrease in intensity of PiIN coming from saturation transfer, the apparent unimolecular rate constant of PiIN to ATP was calculated to be 0.6 +/- 0.15 sec-1.


Antibody-induced linkages of plasma membrane proteins to intracellular actomyosin-containing filaments in cultured fibroblasts.

The surface distributions of three different membrane integral proteins, beta2-microglobulin (part of the histocompatibility antigen complex), aminopeptidase (alpha-aminoacyl-peptide hydrolase; EC 3.4.11.2), and the Na+,K+-ATPase (ATP phosphohydrolase; EC 3.6.1.3) on human fibroblasts grown in monolayer culture have been studied with their specific antibodies by immunofluorescence. On the same cells, the distribution of intracellular actin was observed by a spectrally distinct fluorescent staining procedure. If each of the antibody reagents was permitted to cluster its specific protein in the plane of the membrane, these clusters apparently became linked, through the membrane, to actin- and myosin-containing filaments (stress fibers) underneath the membrane, and were thereby immobilized. From these and other experiments, it appears that most, if not all, integral proteins can, upon clustering, form such transmembrane linkages to actin and myosin. A molecular mechanism for the formation of these linkages is proposed which postulates that actin is associated with the cytoplasmic surface of plasma membranes by peripheral attachment to a ubiquitous integral protein X in the membrane; when other integral proteins are induced to form clusters, they become bound to X and hence to actin (and myosin). The possible physiological role of these transmembrane linkages is briefly discussed.


Calcium-dependent adenosine triphosphatase activity preservation in isolated sarcoplasmic reticulum.

ATPase activity in sarcoplasmic reticulum vesicles was measured before and after storage for several weeks and under a variety of conditions. Rapid freezing and storage at-80 degrees C provided optimum protection of enzyme activity. Sarcoplasmic reticulum preparations stored at 0 degrees C or frozen slowly and stored at-20 degrees C were not stable. At 0 degrees C sucrose, glycerol, and dithiothreitol had a stabilizing effect while NaCl, dimethylsulfoxide, and antioxidants afforded little or no protection.


[Incidence and diagnosis of lumbosacral pouch diverticula].

The myelograms of ninety-nine patients with an ischias symptomatology were analyzed. In fifteen of the subjects there were found lumbosacral radicular pouch diverticula which, after elimination of other nosogenic factors, were considered chiefly responsible for the clinical and neurological pictures observed in six cases. The pathological and anatomical, clinical and radiographic results described by the authors represent a disease picture which is little known and, hence, not generally included in the differential diagnosis of ischialgia, but which has been found to yield to neurosurgical treatment in selected cases.


Enhancement of lung colony-forming efficiency by local thoracic irradiation: interpretation of labeled cell studies.

The dynamics of 125IUdR-labeled tumor cell retention in the lungs have been compared with the efficiency of lung colony formation over a wide range of inoculum sizes in normal mice and in mice pretreated with 1000 rads local thoracic irradiation (LTI). These studies indicate that the increase in lung colony yield after LTI cannot be ascribed to improved intravascular trapping or interstitial lodgement of tumor cells. Hypotheses purporting that active specific or nonspecific host defense might be impaired by LTI were reassessed but rejected in favor of the idea that radiation-induced alterations in the physiological mocroenvironment of the lungs improve an intrinsically poor survival capability of intravenously disseminated tumor cells.


The preexcitation syndromes.

Current methodology permits one to define the functional basis of the preexcitation syndromes with reasonable certainty and to develop a rationale for instituting trials of medical therapy. Future studies will hopefully result in a more exact definition of the anatomic substrates of preexcitation and their relationship to the pathophysiology of the associated syndromes. New antiarrhythmic agents must also be developed to add to the relatively small number of available drugs. Important questions still remain. Should asymptomatic patients with preexcitation be studied? If found to demonstrate potential for malignant arrhythmias, should they be treated prophylactically? The answers to these questions will require study and long-term follow-up of nonhospital referral patients. Surgery offers a feasible therapeutic alternative for patients with life-threatening or disabling arrhythmias but demands a team equipped to perform precise preoperative and intraoperative mapping studies to define the type and location of underlying anatomic substrates.


Validity of the "airflometer"--a simple device for assessment of forced expiration.

The device is basically a plastic turbine with a reduction gear (approximately 1:300) driving an indicator. Following a forced expiration on the indicator comes to rest after about 30 s, when it is read. The reading appears to be generated by the expired flow versus time pattern, and during a forced expiration, close to maximum speed for the turbine is reached within 0.5 s. In a given subject repeated measurements with the same apparatus varied within a few per cent, whereas the variation was considerable among different apparatuses. Readings correlated about equally well with FEV0.5 and FEV1.


Use of a new simple device, the airflometer, in detecting changes in airways obstuction.

A simple device for measuring ventilatory function, the airflowmeter, was found to be at least as sensitive as the Wright peak-flow meter in detecting histamine-induced bronchoconstriction in asthmatic patients. The apparatus also was found suitable for monitoring ventilatory function by the patients themselves at home.


[Chordomas. Excision of a lumbar chordoma: 2 1/2 years survival without signs of recurrence and without functional complications].

In connection with surgical removal of a chordoma in the lumbar region by large excision, followed by 31-month survival of the patient without complications, personal experience of 8 chordomas operated on over the last 20 years is reported. The authors believe their observations show the value of active surgical treatment combined with radiotherapy, which has a palliative effect on the pain and slows the evolution of the tumor. The effectiveness of surgical treatment and radiotherapy leads the authors to challenge the negative attitude generally taken towards the treatment of this condition and to adopt a position of moderate optimism.


The motor unit: anatomy and histochemical functional correlations.

The glycogen depletion technique has demonstrated the distribution of fibres in normal and reinnervated motor units, the histochemical uniformity of its fibres and enabled direct correlation between histochemistry and function. Homogeneity exhibits the capacity of the motoneurone to determine histochemical and related functional properties of its muscle fibres at a specific level. Changes in rat soleus motor units during growth indicate mechanisms by which the motoneurone is able to alter this level even qualitatively in order to adapt the muscle to its usage.


[Indications for and dangers of methods for gastroenterological endoscopy].

The value of modern fiberoptic endoscopy is discussed by comparing negative and positive aspects of both radiology and endoscopy. A detailed analysis is provided of the complications observed in 16,477 invasive gastrointestinal investigations performed over the last 11 1/2 years in our unit. The morbidity was 0.1% in 5886 large bowel examinations and 0.2% in esophago-gastroduodenoscopy and in all 2871 investigations involving invasive liver-pancreas diagnostics. The overall mortality was 0.06%. It is emphasized that in invasive gastrointestinal examinations elderly and debilitated patients are at risk, whereas the danger is minimal for patients in reasonable health.


Membrane enzymes: artifacts in Arrhenius plots due to temperature dependence of substrate-binding affinity.

For the membrane sodium-stimulated magnesium-adenosinetriphosphatase of Acholeplasma laidlawii B both the Vmax and Km values in the Michaelis equation very strongly with temperature. Simulations of Arrhenius plots show that an enzyme with a temperature-dependent Km can yield a variety of Arrhenius plot artifacts, most notably erroneous "breaks," if activity is assayed at a fixed substrate concentration.


A morphologic study on the effect of suturing the submucosa of the large intestine.

Five suture materials, chromic catgut, braided silk, Prolene, Teflon coated braided Dacron and Dexon have been examined morphologically for their effect on the submucosal collagen structure of the large intestine. The rougher surfaced materials, such as catgut, braided silk and Dexon, cause considerable damage to the submucosa on either side of an intestinal anastomosis. Because of this damage, it would appear that these sutures are more likely to jeopardize the integrity of an intestinal anastomosis.


Serine protease specificity for peptide chromogenic substrates.

Rates of hydrolysis of the newly developed peptide chromogenic substrates S-2160 (N-Bz-Phe-Val-Arg-pNA, HCl), S-2238 (H-D-Phe-Pip-Arg-pNA, 2HCl), S-2222 (N-Bz-Ile-Glu-Gly-Arg-pNA, HCl), and S-2251 (H-D-Val-Leu-Lys-pNA, 2HCl) from AB Kabi Peptide Research and Chromozym TH (Z-Gly-Pro-Arg-pNA, HCl) from Pentapharm Limited were tested against highly purified preparations of human plasmin, bovine trypsin, human alpha thrombin, and bovine factor Xa. S-2160, S-2238, and Chromozym TH are sensitive to thrombin, Chromozym TH and S-2238 exhibiting a substantially greater sensitivity than S-2160. All 3 substrates are insensitive to factor Xa but hydrolyzed to varying degrees by plasmin and trypsin. In contrast, S-2222 is sensitive to Xa and insensitive to thrombin. S-2251 is relatively plasmin-specific, being resistant to the clotting enzymes thrombin and Xa. S-2251 exhibits even greater sensitivity to the SK-plasmin complex than to plasmin. In addition, the substrate Chromozym PK (N-Bz-Pro-Phe-Arg-pNA, HCl) was evaluated and found to be relatively specific for plasma kallikrein. Assays for antithrombin III and heparin using S-2222 as the substrate and factor Xa as the enzyme, plasma plasminogen and plasmin inhibitors using S-2251 as the substrate, and plasma prekallikrein and kallikrein inhibitors using Chromozym PK as the substrate have been developed. Synthetic peptides mimicking amino acid sequences adjacent to proteolytic activation cleavage of plasma serine protease precursors appear to be sensitive and relatively specific tools applicable to kinetical and clinical studies of these enzymes and their inhibitors.


Degradation pathway of fibrinogen by plasmin.

The molecular weights of derivatives obtained from chemical and enzymatic degradation of fibrinogen and fibrin support a model in which the two halves of the fibrinogen molecule are covalently linked by a set of disulfide bonds at the amino-terminal region. The 2 asymmetric cleavages caused by plasmin in the fibrinogen molecule occur according to the reactions: X leads to Y + D Y leads to E + D. The quantitative analysis of the amino-terminal amino acids in fragments D (from fibrinogen) and DD (from crosslinked fibrin) yields a total of 3.0 and 6.9 moles of amino acids per mole of protein, indicating three and six polypeptide chain structures, respectively. The data on molecular weights, polypeptide chain composition and immunologic properties of fibrinogen degradation products support the hypothesis on the asymmetric pathway of fibrinogen degradation by plasmin and the formation of two fragment D and one fragment E molecules from each molecule of fibrinogen.


The intravascular generation of fibrinogen derivatives and the blood vessel wall in venous thrombosis and disseminated intravascular coagulation.

Both deep venous thrombosis and DIC are intermediate mechanisms of disease--both are a consequence of the deposition of fibrin-rich material in blood vessels some distance from the primary site of tissue destruction. The great difference in the sites of fibrin deposition may depend on the extent and site of activation of the clotting mechanism. DIC likely occurs in the fluid phase of the blood as a consequence of massive fibrin formation while thrombosis results from limited fibrin formation at the interface between blood and vessel wall. Leukocytes may be essential for attaching thrombi to the vessel wall in many places.


[Experiences on preclotting of vascular dacron protheses with and without addition of factor XIII (author's transl)].

Dacron vascular prostheses were preclotted with and without addition of human fibrin stabilizing factor (factor XIII). In our scanning electron microscopic examinations we found amorphous fibrin achieving a three dimensional net structure in the prostheses after addition of factor XIII.


Mixed lymphocyte culture responses in combined immunodeficiency of horses.

Combined immunodeficiency in horses is a genetic disorder in which there is a defect in the production of committed B and T lymphocytes. In this study, peripheral blood mononuclear leukocytes from foals with combined immunodeficiency were examined for their capacity to stimulate and respond in one-way mixed lymphocyte cultures. Irradiated cells from combined immunodeficient foals were uniformly capable of stimulating cells from unrelated horses. However, none were able to respond to allogeneic stimulation. Examination of cells from known carrier horses revealed no difference in capacity to stimulate or to respond in mixed lymphocyte culture compared with noncarrier horses.


Growth and rejection patterns of murine lymphoma cells antigenically altered following drug treatment in vivo.

Murine leukemia cells transformed by in vivo treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) are rejected by histocompatible recipients following inocula of 10(7) cells i.p. Progressive tumor growth or tumor growth and regression was monitored measuring the extent of DNA synthesis in the peritoneal cavity of mice using the [125I]5-iodo-2'-deoxyuridine uptake method. In addition, the results were confirmed by cell count and mortality data. Comparable growth rate was found initially in both DTIC and parental lines in histocompatible hosts. Later, mice challenged with parental lines died, whereas hosts inoculated with DTIC-treated sublines rejected the tumor. On the other hand, lethal growth occurred in mice inoculated with DTIC-treated sublines when immunodepressed by cyclophosphamide given before tumor challenge, or by methotrexate given after challenge of a methotrexate-resistant DTIC-treated subline. The similarity between the growth rate of the parental and DTIC-treated lines in histocompatible hosts does not support the hypothesis of impaired "oncogenic potential" of such DTIC-treated lines. Furthermore, the growth and rejection pattern of a parental line in H-2-incompatible hosts was similar to that observed for DTIC-treated lines in histocompatible hosts, suggesting that comparable immune mechanisms were involved in both cases.


Complete typing of the HLA region in families. III. Analysis of responses in the primed lymphocyte test (PLT).

LCA, a rapid and efficient computer method to allocate blastogenic responses to positive and negative clusters, is described. The method involves the selection of a partition level for an ordered array of values, such that the resulting two clusters have minimal "within-cluster" variances. Individuals to whom the program assigned the same two HLA-D antigens were MLC-identical (cluster 0) in 50% of the cases. This proportion was lower for HLA-D-identical pairs that typed for Dw4 and/or Dw7, indicating that these antigens are less well defined than the rest. PLTs were less efficient than HTCs in HLA-D typing due to the induction of extra (non-HLA-D determined) responses in the higher cluster.


[Double autosomal aberration: trisomy 21 and familial reciprocal translocation t(10;12)(p14;q21)].

A child with the Down syndrome revealed besides a regular trisomy 21, an enlargment of the short arm of chromosome 10, and the deletion of the long arm of chromosome 12. The proband's mother, who was phenothypically normal woman, appeared to be a carrier of the reciprocal translocation, her karyotype being: 46, XX, rep (10;12) (10qter leads to leads to 10p14; 12q21 leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter). Hence, the proband had double chromosomal aberration 47, XX, +21, rcp (10; 12) (10qter leads to 10p14 : 12q21 leads to leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter) mat. There is no reason to relate hard manifistation of the Down syndrome with the detected translocation. The influence of the mathernal non-devision in the meiosis and the rise of the trisomy 21 is discussed. In the following pregnancies it is advisable to amniocentesis.


[Cytochemical study of the different stages in the life cycle of Toxoplasma gondii. IX. The polysaccharides and lipids in the parasites at developmental stages from the cat intestine].

Amylopectin was detected in all the stages examined. In the oval stages the minute granules of PAS-positive material were seen in the cytoplasm when examined on fresh-frozen sections. In merozoites, amylopectin was more conspicuous with maturation. The residual body of microgametocytes contain large amounts of amylopectin; no polysaccharide was visualized in microgamete bodies. Amylopectin was most abundant in macrogametocytes and zygotes. However, no peripheral position of PAS-positive "plastic granules" (wall-forming bodies), so characteristic of other coccidia and revealed by the electron microscopy for T. gondii macrogametocytes, was seen. Acid mucopolysaccharides in the macrogametocyte were detected in the central zone, leaving the periphery of the cell unstained. Very small, if any, amounts of lipids were detected in asexual stages of T. gondii. Unlike, large accumulation of lipid droplets were seen in growing macrogametocytes suggesting the involvement of lipids along with amylopectin in the metabolism of oocysts later discharged from the host body.


Antisera with Ia specificity selected by lymphocytes from patients with chronic lymphocytic leukemia.

Cells from patients with chronic lymphocytic leukaemia (CLL) have been used to screen the sera of pregnant women for antibodies specifc for B lymphocytes. The sera have been divided into groups showing Ig specificity: group I (UK 3) had a positive association with HLA-B8 and DW3, and group II (UK 2) with HLA-B7 and DW2. Groups III, IV and X were independent of each other and of HLA-A, B and C locus antigens. Certain sera with B-cell activity showed specific blocking activity in the mixed lymphocyte reaction (MLR), and this activity was dependent on the Ia sepcificities and DW specificities of cells used in the MLR. Some sera specifically blocked the responding cells, other the stimulating cells.


[Niacin allowance of students of a sports college].

In 227 students of the Institute for Physical Culture examined in the winter-spring and summer-fall seasons of the year, the passage of N1-methylnicotinamide (MNA) with urine per hour on an empty stomach amounted to 245 +/- 15.9 and 311 +/- 14.6 microgram/hour (the difference according to seasons in significant). These figues point to the dependence of the MNA excretion with uridine on the quantity of the niacin equivalents supplied together with the food. The content of such equivalentsin the rations of students-sprotrsmen (7-9.5 mg per 1000 calories per day) proved insufficient to maintain the MNA passage with urine at a level accepted as a standard allowance of niacin for the organism, i. e. 400-500 microgram/hour. Furthermore, the author shows changes in the niacin allowances of the student's organism, engaged in different kinds of sporting activities and also depending upon the sporting qualification of the examinees the work performed by them, the periods of training, and conditions of their every-day life.


[Primary idiopathic myocardiopathies].

Forty eight cases with primary idiopathic myocardiopathies were diagnosed in clinical conditions for a period of 2 years. Among the patients, being mainly young, at the age of 17-20--hypertrophic myocardiopathies predominated (44 cases), 27 of them were obstructive forms. Modern investigation methods were used in making the diagnosis of the cases, including cardiac probe with angio--and ventriculography, isotope gamma cardiographic, echocard ographic investigations as well as pharmacodynamic follow up of murmur findings with alfa beta blockers. Pseudoinfarction ECG images in young people, presence of systolic murmur of expulsion with p.m. at B. Erb and X-ray data for symmetric or asymmetric hypertrophy of the heart were the indicating sings for the diagnosis. The presence and recording of expulsion murmurs is stressed upon in making the diagnosis of those diseases which after alfa and beta blockers alter their intensity and character, the infarction-like ECG and especially the significance of echocardiography.


[Problems in splenic cysts--a case contribution].

It is reported on a cyst of the spleen in a twenty-nine-year-old female patient in whom as accidental findings a splenomegaly was established. The diagnosis would be ascertained by means of laparoscopy and laparotomy. The genesis of the cyst remained unclear. The author deals with the problems of the differential diagnosis.


[Experimental findings in liver perfusion measurements using an ultransonic Doppler flowmeter].

1. The ultrasonic doubling method of bloodflow measurement is an experimental easily practicable and very exactly recording measurement arrangement. By this method data of other methods were extended and ensured. 2. Early inquested finding is attested that after inhibition of portal vein bloodflow and after portocaval anastomosis an increased arterial perfusion of liver through a. hepatica is following. Increasing bloodflow of a. hepatica is independent of cardiac output. 3. After diminution of arterial perfusion by occlusion of a. hepatica no increased portal bloodflow is following. 4. It is to suppose an "intrahepatic regulation of liver bloodflow". It seems economical that the perfusion part of the a. hepatica with her higher oxygen content is increasing when the general perfusion is decreasing by diminished portal bloodflow or diminished blood pressure. So far it is impossible to interpret whether this accomodation is based on a difficult "auto-regulation" or is originated pressure passive from the flow together of two systems are staying under different pressure.


[On the value of the magnifying optic of Lent in laparoscopy) (author's transl)].

103 non selected patients underwent laparoscopy with the photolaparoscope equipped first with Luminaoptic and subsequently with the magnifying optic of Lent (Wolf GmbH, Knittlingen, W-Germany). The results are compared with the histologic findings and among each other. In 83.5% there was a satisfactory correlation between laparoscopy and histological findings, in 16.5% there was none. It was only in 2.9% of all cases that a different diagnosis resulted by means of the magnifying optic. From these results it is concluded that the magnifying optic does not provide a higher effectivity of laparoscopy. Thus the magnifying optic should be preserved for instruction.


The effect of 1-methoxypropylpropylnitrosamine in Syrian golden hamsters.

The carcinogenicity of the alpha-dipropylnitrosamine (DPN) methyl-ether, 1-methoxypropylpropylnitrosamine (1-MPPN), was investigated in Syrian hamsters for comparison with the effect of the alpha-DPN acetylester, 1-acetoxypropylpropylnitrosamine (1-APPN). It seemed possible that 1-MPPN, 1-APPN and DPN could form a common intermediate. However, contrary to the effect of 1-APPN, no tumors were found at the injection site after subcutaneous 1-MPPN treatment. The main target organ for 1-MPPN was the respiratory tract (as with DPN) and the lungs were greatly affected. In addition, pharyngeal and forestomach tumors occurred, and these were not observed after DPN administration. The results of 1-MPPN treatment, relative to DPN and 1-APPN, are discussed.


Carcinogenicity of 1-oxopropylpropylnitrosamine (N-nitroso-N-propyl-proprionamide) in Syrian hamsters.

The effect of 1-oxopropylpropylnitrosamine (1-OPPN) was examined in Syrian hamsters. The subcutaneous (s.c.) LD50 was 308 mg/kg b.w. Animals treated s.c. once with a high dose of 1-OPPN had subcutaneous sarcomas and vaginal papillomas. Weekly s.c. injections for life led to high incidences of sarcomas at the injection site. In addition, 1-OPPN had a systemic effect. Neoplasms developed in the nasal cavity, larynx, trachea, lungs forestomach, and vagina. The results are discussed in connection with those found with other DPN derivatives substituted in the alpha-position.


Urinary bladder neoplasms in Syrian hamsters after administration of N-nitroso-N-methyl-N-dodecylamine.

The biological effect of N-nitroso-N-methyl-N-dodecylamine (NMDA) was examined in Syrian hamsters as part of a comparative study. Data obtained show that after intragastric administration of NMDA, the urinary bladder was the main target organ for the carcinogenic effect. Transitional cell neoplasms developed and a positive dose response relationship was observed. Lung tumors occurred only in female hamsters, whereas males more frequently showed neoplasms of the nasal cavity and digestive tract.


Experimental induction of melanotic tumors in syrian golden hamsters by transplacental and topical application of ethylnitrosourea.

Pregnant Syrian golden hamsters were treated with a single intra-peritoneal injection of ethylnitrosourea (ENU) solution a few hours pre-parturition. Offspring either received no further treatment or from 6 weeks of age, bi-weekly application of ENU solution in acetone for 20 consecutive weeks. Progeny from non, transplacentally treated mothers were also treated topically. Among all treated groups, 8.6% of the animals developed pigmented skin tumors, most of these animals having received the combined treatment. This group also showed a significantly decreased latency period in females compared to males. One of the skin tumors, which was histologically and clinically benign, was transplanted several times and subsequently exhibited malignant features.


Adenocarcinomas of the stomach induced in beagle dogs by oral administration of N-ethyl-N'-nitro-N-nitrosoguanidine.

Two 8-month-old and two 4-month-old male beagle dogs received 250 ml of 150 microgram/ml solution of N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) and 2% Tween 60 mixed with a pellet diet twice a day for 8 months as the same methods used for mongrel dogs in our first report [Juntendo Medical Jouranl 19, 579-583 (1973)]. Gastric carcinomas with distant lymph nodes metastases occurred in three beagle dogs except for one died from anesthesia at the endoscopy. Metastases to the liver were observed in two beagles. In the most long-lived beagles, peritonitis carcinomatosa with ascites and metastases to the liver, lungs, bones, and skin were found. Main gastric tumors were located at the subcardia in two dogs (elevated tumor in dog No. 6, ulcerated tumor in dog No. 8), but in dog No 7 at the angulus (ulcerated tumor). Histologically, carcinomas were composed of poorly differentiated adenocarcinoma, signet-ring cell carcinoma, tubular adenocarcinoma, and undifferentiated adenocarcinoma. In all of three dogs which developed adenocarcinoma of the stomach, Stewart's criteria were completely satisifed. Using our methods the target organ is limited only to the stomach, without any sarcomatous lesion of the intestines.


The carcinogenic effect of beta-oxidized dipropylnitrosamine in mice. I. Dipropylnitrosamine and methyl-propylnitrosamine.

Di-n-propylnitrosamine (DPN) and methyl-n-propylnitrosamine (MPN) induced mainly respiratory tract neoplasms in female NMRI mice after subcutaneous administration. The majority of tumors occurred in the nasal cavities, although significant incidences were also found in the larynx, trachea and stem bronchi. Treatment with both substances additionally resulted in vascular neoplasms of the liver, while DPN only caused tumors in the pharynx, esophagus and forestomach.


Chromosomes of lymph node metastases derived from Ehrlich ascites carcinoma cells inoculated into rats.

The inoculation of Ehrlich ascites carcinoma cells in irradiated and cortisone-treated rats induced an ascitic tumor and lymph node metastases. Chromosome banding analysis showed that metastatic lymph nodes are composed of Ehrlich tumor cells and normal rat metaphases, derived from reactive host cells.


Melanogenesis in genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids: correlation between tyrosine activity and degree of malignancy.

In the genetically determined pigment cell tumors of platyfish and platyfish-swordtail hybrids, the degree of malignancy of pigment cells which have been neoplastically transformed by a tumor gene (Tu) depends on the type and number of certain regulating genes (R). In the present study, the tyrosinase activities in tumors of different degrees of malignancy (black spots, premelanomas, melanomas) have been determined. The results demonstrate a close correlation between the level of tyrosinase activity and the degree of malignancy. Spot patterns consisting of completely differentiated (benign) Tu-transformed cells show no tyrosinase activity. Premelanomas containing a few incompletely differentiated (malignant) Tu-transformed cells in addition to many differentiated ones show moderate tyrosinase activities. Melanomas which contain increasing numbers of incompletely differentiated cells with increasing growth rates show high to extremely high tyrosinase activities. Thus, the tyrosinase levels present in these tumors can be used as an indicator for the degree of differentiation and, thereby, for the degree of malignancy of the neoplastically transformed pigment cells.


[Combination chemotherapy in patients with disseminated bronchogenic carcinoma (author's transl)].

49 patients with disseminated bronchogenic carcinoma (small cell, 16;squamous cell, 17;large cell, 12;adeno, 4) were treated with a combination of adriamycin, cyclophosphamide, vincristine and DTIC. In a randomized series (21 patients) chemotherapy alone was compared to chemotherapy plus heparin. Partial remission was achieved in 8 patients with small cell carcinoma, in 5 patients with large carcinoma and in 2 patients with squamous cell carcinoma. The survival of patients who responded to therapy was greater than the survival of patients who did not respond to therapy. The duration of remission and the survival time was not longer in patients who had additional heparin therapy.


Cystostatic efficacy of DNA-complexes of adriamycin, daunomycin, and actinomycin D. II. Comparative in vivo studies in an Ehrlich-ascites tumor.

The cytostatic efficacy of the antibiotics adriamycin, daunomycin and actinomycin D and of DNA-complexes of these compounds was compared in an Ehrlich ascites tumor in vivo. Various doses of the individual drugs and their DNA-complexes were injected intraperitoneally into female NMRI mice following 8 days after inoculation of 10(6) Ehrlich ascites cells. Survival analyses of animals demonstrated that by addition of DNA therapeutic indices were improved for adriamycin, daunomycin and actinomycin D, DNA alone had no effect on this tumor. Since earlier biochemical data (Seeber et al., 1977) had shown decreased in vitro cytotoxicity of DNA-bound antibiotics, this increase in therapeutic efficacy is probably due to an altered pharmacological behaviour after complex formation with a prolongation of effective intraperitoneal drug levels and decreased systemic toxicity.


Tumor induction by a single subcutaneous injection of N-methyl-N'-nitro-N-nitrosoguanidine and its derivatives in newborn mice.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG), or its derivatives N-hexyl-N'-nitro-N-nitrosoguanidine (HNNG) and 1,6-bis(N'-nitro-N-nitrosoguanidinyl)-n-hexane (HxBNNG) were given to newborn ICR/JCL mice by a single subcutaneous injection in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of MNNG, HNNG or HxBNNG was 62 microgram/g, 555 microgram/g, or 500 microgram/g of body weight, respectively. In a chronic study, a single subcutaneous injection of MNNG to newborn mice at a dose of 62, 31, or 3 microgram/g of body weight induced tumors of the lung and hemangioendotheliomas in both sexes, and tumors of the liver in males. Other pathologic findings, such as deformities of the spine and alopecia of the skin, were frequently observed. The incidences of tumors in each group were clearly dose related. HNNG and HxBNNG were not tumorigenic within the observation period.


Occurrence of volatile N-nitrosamines in animal diets.

46 samples of commercially available diets for experimental animals have been analysed for their content of volatile N-nitrosamines by use of a nitrosamine-specific detection method (TEA-detector). 80% of all analysed samples were positive for N-nitrosodimethylamine with a maximum content of 79 ppb (microgram/kg) found in one sample. 59% of the samples were positive for N-nitrosopyrrolidine with 26 ppb as highest content. In 3 samples trace quantities (less than 1 ppb) of N-nitrosodiethylamine were found, one sample contained N-nitrosopiperidine (4 ppb).


Detection of induced resistance in short-term-tests. Adriamycin-resistant sarcoma 180.

By treatment of the sarcoma 180 (ascites) with adriamycin over 30 passages in NMRI mice, an adriamycin-resistant tumor cell line was developed. The resistance could be detected both in animal experiments and in the short-term test. In spite of treatment of the sarcoma 180 with triaziquone over 50 passages, no resistance could be detected against triaziquone either in the in vitro test or in animal experiments. The necessary criterion for a pretherapeutic test of sensitivity or resistance--a good correlation between in vivo and in vitro results--was fulfilled in all experiments carried out.


[A comparative clinical and pathological study on the classification and prognostic features of 57 thymomas. II. prognostic features (author's transl)].

The most important prognostic determinants of the thymomas are the gross findings at operation (equal to the presence or absence of gross invasion of adjacent tissue) and the presence or absence of the thymoma-associated systemic disease, particulary myasthenia gravis. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical thymomas. Thirty-four of 57 patients with thymomas were females and 23 males. The tumors in 40 cases were non-invasive thymomas, and in 17 cases the tumour were invasive of adjacent tissue. 35.1 percent of patients were asymptomatic, the tumours being discovered on roentgenograms done on a routine basis or for an unrelated porpose. 40.3 percent of patients have had a thymoma-associated systemic disease. The most common presenting symptoms were related to myasthenia gravis (26.3%). The 5-year survival rate was 90 percent for non-invasive thymomas without myastenia gravis and 50 percent for invasive thymomas. The 5-year survival rate for patients with myasthenia gravis and encapsulated (non-invasive) thymomas was approximately 60 percent, whereas that for invasive thymomas with myasthenia gravis was 40 percent. The primary form of therapy for all thymomas is the surgical excision. In cases with invasive and/or metastasizing thymomas, postoperative radiation and adjuvanted chemotherapy is indicated, but in most series, the longterm results of this form of therapy are discouraging.


Phagocytosis of monocytes in cancer patients.

The phagocytic activity of monocytes directed at yeast particles was investigated in patients with untreated malignant tumors and in normal controls. Phagocytic activity was found to be significantly increased in the patients. It could be shown that the increased activity is caused by factors contained in the patient's plasma. These factors are only partly destroyed by heat inactivation, suggesting that both heat labile and heat stabile factors are contributing to the observed enhancing effect on phagocytic activity. The heat labile portion could well be the complement component C5, while the heat stabile portion is so far undefined.


Experiments on the carcinogenic effect of ortho-toluol-sulfonamid (OTS).

Ortho-toluol-sulfonamid was applied to male and female Sprague-Dawley rats in daily doses of 200 mg/kg and 20 mg/kg bodyweight respectively. The maximum dose applied amounted to 17 g/kg. A shortening of the average life expectation was not observed in comparison to the control animals. The incidence of malignant tumors in the animals treated with OTS was identical with the one of the control animals. We did, however, find one animal in the test groups that had a carcinoma of the urinary bladder and seven animals with papillomas of the bladder.


[Control mechanisms of the ribonucleotide reduction in mammalian tissue (author's transl)].

The ribonucleoside diphosphate reductase (E.C.1.17.4.1) was partially purified from Ehrlich ascites carcinoma and regenerating rat liver. The specific activity of the two enzyme preparations did not vary with regard to the reduction of UDP, ADP, CDP and GDP. Similarly the regulation of the enzyme system by deoxyribonucleoside triphosphate (dNTP) is almost identical. Through the application of deoxyribonucleosides (10(-3) or 2 x 10(-3)M) and measurement of the dNTP content it was found in Ehrlich and Yoshida ascites tumours that these control mechanisms are transmissible to whole cells. dATP inhibits the reduction of all four nucleoside diphosphates. dTTP stimulates the reduction of GDP, dCTP that of UDP and dGTP that of ADP.


The natural history of nephrogenic adenoma of the urinary bladder.

The nephrogenic adenoma is a peculiar lesion of the urinary bladder characterized partly by villous and partly by gland-like structures. The two layered surface epithelium consists of an eosinophilic cell layer, which covers a clear cell layer, the latter resting upon a delicate basal layer. The clear cells disappear when approaching the tip of the villi. There exists a 200 micron wide zone of transition between the urinary bladder epithelium and that of the neprogenic adenoma. At the base of the villi there are scattered nodules of gland-like structures lined either by eosinophilic cells or by clear cells. These epithelial cells are derived from the corresponding surface epithelial cells from which they had separated by active downwards growth.


[Interaction of p-Dimethylaminoazobenzene with rat liver-chromatin and non-histones (author's transl)].

The carcinogenic p-Dimethylaminoazobenzene and the non-carcinogenic p-aminoazobenzene were radioactive labelled and applicated to Whistar rats intraperitoneally. A very significant difference in binding tendencies for the two compounds and their metabolites was observed in rat liver tissues, rat liver nuclei and rat liver chromatin. Above all a specific binding affinity of the carcinogen to nuclear non-histone protein was found.


[Carcinogenic activity of benzyl-nitrosourea (BzNH) in BD-rats (author's transl)].

Chronic weekly oral and subcutaneous administration of N-Benzyl-N-nitrosourea induced carcinomas of the forestomach and local s.c. sarcomas respectively in BD-rats. This confirms a local carcinogenic effect of the compound. In prenatal experiments in BD-rats no carcinogenic effect of BzNH could be found.


Oncogenic properties of transplacentally acting ethyl-nitrosourea in NMRI-mice after antecedent X-irradiation.

The successive application of X-irradiation and ethylnitrosourea during the fetal period in NMRI-mice results in tumorous as well as in degenerative diseases in offspring. Leukemia and ovarial tumor incidences are increased when compared with animals either treated alone, whilst lung and liver tumors appear at a lower rate. Liver necroses and kidney cysts are further outstanding pathological findings after combined treatment. These results can be parallelled with the known postirradiational proliferative capacities of the affected fetal tissues, and possibly are a sensitive indicator for such radiation induced alterations.


[A comparative clinical and pathological study on the classification and prognostic features of 57 thymomas. I. Microscopy and ultrastructural pathology (author's transl)].

Fifty-seven thymomas, defined as neoplasms of the epithelial-reticular framework cells of the thymus, were assessed in respect to histologic type, inclusive of there ultrastructural aspects. The median age of the 57 patients was 40.4 years, with a range of 2 1/2--72 years. All neoplasms were located in the anterior mediastinum. The tumours in 40 cases were encapsulated and without invasion of adjacent tissue or implants (equal to non-invasive thymomas). The tumors in 17 cases were invasive of adjacent tissue, particularly mediastinal pleura, pericard and trachea. Six of 57 patients (equal to 10.5%) with thymomas have had a thoracic and supraclavicular lymph node metastasis, and osteolytic metastases in the vertebrae and sternum. Thirty-seven (equal to 64.9%) were so-called lympho-epithelial, 7 (equal to 12.3%) pure epithelial, 4 (equal to 7.0%) atypical (or anaplastic) with granulomatous focuses, 3 (equal to 5.3%) carcinoid and one (equal to 1.8%) seminomatous tumors. One patient have had a thymic cyst as a tumor-like conditions of the thymus, and four patients (equal to 7.0%) have had a thymo-lipoma. The histologic type of thymoma had no proof value in predicting prognosis with the exception of the so-called atypical or anaplastic thymoma. The fine structural aspects of thymomas and the fine structural differential diagnosis of anterior mediastinal tumors are discussed.