An electron microscopic study of the location of teichoic acid and its contribution to staining reactions in walls of Streptococcus faecalis 8191. The location of the glucosylated teichoic acid in whole cells and isolated walls of Streptococcus faecalis 8191 has been investigated using ruthenium red, gold-labelled concanavalin A and concanavalin A-peroxidase-diaminobenzidine. Dense laminae were revealed in sections of osmium-fixed walls stained with ruthenium red which corresponded to similar regions stained by uranyl and lead. Such regions were not seen after teichoic acid had been extracted, suggesting that the uptake of stain was by teichoic acid. However, these regions were not labelled on exposure to gold concanavalin A or concanavalin A-peroxidase-diaminobenzidine; these stains indicated that teichoic acid was situated between the dense laminae, although the distribution of stain could have been due to the inability of the concanavalin A stains to penetrate deeply. Chemical binding studies showed that the teichoic acid was the major uranyl binding component in isolated walls, from which it might be inferred that teichoic acid was located in the densely staining regions. However, since osmification significantly increased the binding of uranyl (and lead stains) to non-teichoic acid material, such an inference was not necessarily valid. It is concluded that the presence of teichoic acid can be demonstrated in certain regions of the wall by concanavalin A, but its presence in densely staining regions has not been established. These experiments therefore suggest that teichoic acid may not be intimately associated with the mechanisms that generate contrast patterns in stained sections of cell walls of Streptococcus faecalis.


Immunological heterogeneity of pili of Neisseria gonorrhoeae. Sera of rabbits immunized with pili or formalized cultures of Neisseria gonorrhoeae contained pili antibodies. The reaction between pili and specific gamma globulin was followed by direct visual observation with an electron microscope. Using pili from 31 strains and antisera against three strains, only a few crossreactions between pili were observed. From this it is concluded that gonococcal pili are antigenically heterogeneous. However, serum raised with a T3 culture (with no detectable pili) contained antibodies against pili of the homologous T2 strain. It is proposed that the pilus antigen may exist in a form different from the typical pilus in gonococci.


The location of bacterial antigens on sections of Bacillus cereus by use of the soluble peroxidase--anti-peroxidase complex and unlabelled antibody. The location of antigens on sections of bacteria using the soluble peroxidase-anti-peroxidase complex in conjunction with unlabelled antibody is described. Using this technique, spore antigens have been detected in the cytoplasm of vegetative cells during forespore septum formation and subsequent stages of sporulation. Antigenic sites were first associated with poly-beta-hydroxybutyric acid granules and subsequently were found in increasing quantities in the cytoplasm of the sporangium. Vegetative cell antigens were located on the cell wall and in the cortical region during sporulation. During germination antigens were located in the cortical region, and during outgrowth on the cell wall. These findings are discussed in the light of existing biochemical data.


Bone marrow in the Batten-Vogt syndrome. Six children with clinical and pathological features of Batten-Vogt syndrome showed autofluorescent material in bone marrow cells and in 5 of them sea-blue histiocytes were seen. It is suggested that bone marrow examination for sea-blue histiocytes and autofluorescenceis a useful screening test for ceroid-lipofuscinosis.


The metabolism of cyclic-3'-5'-adenosine monophosphate (cAMP) in diseased muscle. Adenyl cyclase (AC) and cyclic nucleotide phosphodiesterase (PDE) have been studied in muscle from patients affected with muscular and neuromuscular diseases as well as in muscle of rats after experimental denervation. A diminution of AC was observed in Duchenne's dystrophy, in neurogenic atrophies, in inflammatory forms, in myasthenia and myotonia. PDE was diminished in Duchenne's dystrophy and increased in all other diseases considered. Both enzymes were increased in rat muscle after nerve transection. The possible mechanism underlying the biochemical alterations observed are discussed including unmasking of extra-activity due to changed metabolic environment, tissue destruction and activation of lysosomal activity.


Iophendylate cisternography in diagnosis of cerebellopontine angle tumors. Report of 60 cases. 60 cases of bilateral cerebellopontine angle pantopaque cisternography done between May, 1972, and April, 1974, are reported. Of these, 9 showed a unilateral acoustic neurinoma of different sizes, 1 showed a bilateral acoustic neurinoma all confirmed by operation. Technical details and advantages of the procedure are discussed. There were no complications related to the procedure.


Histological subtypes and prognostic problems in meningiomas. The incidence of the various histological subtypes of meningiomas was examined in 1238 patients with surgically treated meningiomas, about 80% arising within the cranial cavity. The histological classification used was that of Courville (1950) and Rubinstein (1972), but "angioblastic" meningiomas were segregated into 3 groups: highly vascularized meningiomas, hemangioblastomas, and hemangiopericytomas. Endotheliomatous and transitional forms constituted 85% of the total (71.5% of intracranial tumors), fibroblastic forms 6.6 and 7.5%, respectively, and highly vascularized (endotheliomatous or transitional) meningiomas 5.2% of the intracranial tumors, while true "angioblastic" meningiomas (hemangioblastomas and hemangiopericytomas) amounted to 2.8% of the total (3.1% of the intracranial tumors). 1.2% were "atypical" (so-called malignant) meningiomas; true meningeal sarcomas were excluded. The incidence of recurrence in patients surviving at least 5 years after apparently complete removal of the tumor was 13% for all sites, and 14.2% for intracranial tumors, but almost twice as high after partial removal. There were no significant differences in the recurrence rate and intervals between first and second operation according to the various histological subtypes of meningiomas, except for hemangiopericytomas which recurred with significantly higher frequency and, together with atypical meningiomas, at much shorter intervals than the others. The prognostic significance of some histological criteria in "non-angiomatous" meningiomas was examined in 211 patients surviving at least 5 years after apparently complete removal of the tumor. Among the recurrences, there was a significantly higher degree of cellularity and increased mitotic rate and, probably, of cortical invasion, while nuclear pleomorphism, increased vascularity, and focal necroses showed no definite differences. The presence of mitotic figures alone appeared to be of no prognostic value. While most recurrent meningiomas did not change their basic morphological type significantly, about 12.5% of the recurrences appeared to have a different rate of growth as suggested by increased cellularity and mitotic rates. In 2 cases an isomorphic (benign) meningioma became a true spindle cell sarcoma.


[Syringomyelia and normal pressure hydrocephalus (author's transl)]. A case of syringomyelia with coexisting hydrocephalus is reported and a pathogenic relationship between both conditions is discussed. Gardner proposed that anomalies at the exit of the fourth ventricle produce a communicating syringomyelia. Hakim and Adams maintain that normal pressure hydrocephalus can aggravate this condition by a hydraulic pressure effect which can be stopped by the insertion of a ventriculoatrial shunt with improvement in the clinical picture. This has been our experience in the case reported.


[Long-term treatment with L-DOPA in a case of torsion dystonia (authors transl)]. A 36-year old woman had been able to move from place to place only by crawling until 1971 after she had been treated with L-DOPA, the dose of which was increased to a maximum of 2.5 g daily. Within 4 weeks there was a diminution of her increased muscle tone and she experienced a dramatic improvement in her daily living activities, being able to walk without assistance for the first time in 20 years. This improvement has continued with a daily maintenance dose of 1.25 g. For patients with torsion dystonia, where the so-called myostatic component preponderates, cautious application of L-DOPA seems to be justified and further clinical studies are suggested.


[Scaling of disturbances of attention in neurological patients (author's transl)]. In a previous report two additive scales were developed for measuring susceptibility to stimulation (with 4 experimental stimuli) and reactivity (with 4 types of reactions). The degree of loss of attention in neurological patients as determined by the position of a patient correlates with the frequencies of his reactions. Thus the measurement of frequencies does not add any further information. There is no patterning of reactions due to the different etiology of the disorder of attention. These results support the suggested one-factor theory of attention.


[The pattern of phospholipids during the course of delirium tremens (author's transl)]. Plasma phospholipids were examined in patients with delirium tremens in the acute phase of the disease and after recovery. The levels of lysolecithin, phosphatidylinositol, phosphatidylethanolamine, sphingomyelin and the total of phospholipids were decreased in comparison to normals. Phosphatidylethanolamine, phosphatidylinositol and the total phospholipids were diminished in comparison to patients with liver cirrhoses. Only in the plasma of patients with liver cirrhoses with bad prognosis (hepatic coma) similar low levels of total phospholipids were found. It is concluded from these results, that the synthesis of phospholipids is reduced during delirium tremens.


On the effect of brain phospholipase A1 on specifically labelled glycerophospholipids in the course of subacute sclerosing panencephalitis. The effect of phospholipase A1 of human brain on 1,2-diacyl-sn-glycero-3-phosphorylcholine, -ethanolamine and -serine, specifically labelled with different fatty acids at either the 1 or 2 position, was determined in subacute sclerosing panencephalitis. An increase of approximately 40% in the specific activity of phospholipase A1 could be observed for all substrates investigated during the demyelinating disorder. On investigating the specific activity of the enzyme with various molecular species of phosphatidylcholine and -ethanolamine, labelled at the 1 position with different radioactive fatty acids, we found that the phospholipase A1 preferentially removed those fatty acids from the 1 position of phosphatidylcholines that have the fewest double bonds, while oleic and linoleic acid were released at almost similar rates from phosphatidylethanolamine.


[Cerebrospinal fluid cytological diagnosis of primary and metastatic tumours of the central nervous system (author's transl)]. In the routine cytological examination of the lumbar CSF of 4000 patients, the diagnosis of a tumour was made in 46 cases, most being metastases to the CNS, 20 having meningeal carcinomatosis. There were 9 malignant cerebral tumours of neuroepithelial origin, 2 spinal meningioma and 1 spinal neurinomas. Autochtonous cerebral tumours rarely exfoliate or become differentiated so are more difficult to identify and especially to distinguish from the nonspecific CSF irritation syndrome. On the other hand metastases are morphologically distuinguishable by cell type and the large number of mitoses. Cytological study of the CSF is of great diagnostic value and, in some cases is the only way to make the correct diagnosis.


[A case of Guillain-Barré syndrome following cholera vaccination (author's transl)]. A 45-year-old woman developed bilateral ascending flaccid paralysis after cholera vaccination, 15 days after the first and 1 day after the second injection. The clinical course resulted in nearly complete paralysis of the lower limbs, paresis of the upper limbs and partial involvement of the cranial nerves. There was only slight sensory loss. The CSF revealed no pleocytosis and a protein level of 206 mg/100 ml. Recovery began 2 weeks later and was almost complete after 2 months. Immunological investigations revealed no remarkable changes.


[Mitochondrial changes of the skeletal muscle in the peroneal muscular atrophy (Charcot-Marie-Tooth disease). Histological and electron microscopic studies (author's transl)]. This report deals with two sisters (38 and 44 years old) suffering from Charcot-Marie-Tooth disease. Muscle biopsies were taken from the deltoid and the rectus femoris. In one of the cases a sural nerve biopsy was also made. Light microscopy showed only slight myopathic changes. The histochemical reactions disclosed an increase in lipid deposition and in NADH-TR activity of type 1 fibres. Electron microscopy showed abnormal mitochondrial aggregates, which were surrounded inconstantly by glycogen deposits, especially in subsarcolemmal space. Many of the atypical mitochondria showed paracristalline inclusions within the cristae. The significance of these findings is discussed and compared with similar reports in the literature.


The fetal trimethadione syndrome.

The fetal trimethadione syndrome. Three families are described in which each of the mothers took trimethadione during pregnancy. From a comparison of siblings in each family and of others exposed to trimethadione in utero, a specific phenotype is delineated. Features included in the fetal trimethadione syndrome are developmental delay, speech difficulty, V-shaped eyebrows, epicanthus, low-set ears with anteriorly folded helix, palatal anomaly, and irregular teeth. Additional anomalies in some of the patients include intrauterine growth retardation, short stature, microcephaly, cardiac anomaly, ocular anomaly, hypospadias, inguinal hernia, and simian creases.


Studies of adoptees from psychiatrically disturbed biologic parents. II. Temperament, hyperactive, antisocial, and developmental variables. Temperament, hyperactivity, antisocial behavior, and developmental milestones were assessed in two groups of adoptees by interviewing the adoptive parents. One group, the "experimental," was born of psychiatrically disturbed biologic parents (N = 59). The second group, the "control," had psychiatrically "normal" parents (N = 54). Infants in each group were separated from their biologic parents at birth and had no further contact with them. Male "experimental" adoptees had excess number of temperament traits characteristic of the "difficult" child, as well as an excess of antisocial behaviors when contrasted with male control subjects. No differences between control and experimental females were found for these variables. Hyperactive behavior in the adoptees of each sex was associated more with antisocial parentage than in those of "normal" parentage.


Histochemistry and scanning electron microscopy of tooth integumental material in humans. Plaque material on human teeth was investigated using histochemical techniques and scanning electron microscopy. A positive reaction for protein, cargohydrate, and lipids was seen around the fissures and in a well-defined band around the sides of the tooth corresponding to the highest contour. These regions are the location of dense aggregates of bacteria as seen with scanning electron microscopy. This study emphasizes the fact that considerable attention should be given to the cleaning of not only the occlusal surfaces but also the highest contour of the tooth.


Kinetics and mechanisms of degradation of the antileukemic agent 5-azacytidine in aqueous solutions. The hydrolytic degradation of 5-azacytidine was studied spectrophotometrically as a function of pH, temperature, and buffer concentration. Loss of drug followed apparent first-order kinetics in the pH region below 3. At pH less than 1,5-azacytosine and 5-azauracil were detected; at higher pH values, drug was lost to products which were essentially nonchromophoric if examined in acidic solutions. The apparent first-order rate constants associated with formation of 5-azacytosine and 5-azauracil from 5-azacytidine are reported. Above pH 2.6, first-order plots for drug degradation are biphasic. Apparent first-order rate constants and coefficients for the biexponential equation are given as a function of pH and buffer concentration. A reaction mechanism consistent with the data is discussed together with problems associated with defining the stability of the drug in aqueous solutions. At 50 degrees, the drug exhibited maximum stability at pH 6.5 in dilute phosphate buffer. Similar solutions were stored at 30 degrees to estimate their useful shelflife. Within 80 min, 6 times 10(-4) M solutions of 5-azacytidine decreased to 90% of original potency based on assumptions related to the proposed mechanisms.


Determination of dicumarol metabolites in bile of rats. After intravenous administration of dicumarol-14C to rats, the bile excreted over the next 24 hr contained from 32 to 46% of the administered radioactivity. At least three primary metabolites and a small amount of unchanged dicumarol were present in the bile. Over 91% of the primary metabolites was converted to dicumarol and 7-hydroxydicumarol by hydrolysis with beta-glucuronidase. Some primary metabolites were hydrolyzed simply by acidification to pH 3 or by treatment under the acidic conditions utilized in the enzymatic hydrolysis. The three primary metabolites contain carboxylic acid groups, as indicated by their electrophoretic mobility-pH profiles, and some are simple glucuronides of dicumarol and 7-hydroxydicumarol. The possibility that others are derivatives of these compounds in which a coumarin lactone ring is opened cannot be ruled out. When the metabolites released by either acidification or enzymatic hydrolysis were chromatographed in n-butanol-3 M ammonia, artifacts were produced, presumably as a result of decomposition of 7-hydroxydicumarol. The question is raised whether a previously reported metabolite (B055) is an artifact.


Facile preparation of 6-chloro-9-amino-2-hydroxyacridine, a urinary metabolite of quinacrine and quinacrine mustard. 6-Chloro-9-amino-2-hydroxyacridine was found to be a metabolite of both quinacrine and the antimalarial alkylating agent quinacrine mustard. Its structure was confirmed by a one-step reaction of quinacrine with 48 percent hydrobromic acid. The presence of this compound as a metabolite of quinacrine mustard suggests a possible in vivo activation mechanism for its antitumor activity and a pharmacological basis for its toxicity to the liver. In vitro experiments showed that this new compound does react with chromosomes and, therefore, can be both a useful chromosome stain and an intercalating agent.


The effects of ganglionic blockade, reserpine and vinblastine on plasma catecholamines and dopamine-beta-hydroxylase in the rat. In rats, chronic ganglionic blockade induced by repeated doses of chlorisodamine rapidly and profoundly lowered plasma norepinephrine, but plasma dopamine-beta-hydroxylase (DBH) activity, even after 5 days treatment, was not significantly reduced. Long-term chlorisondamine treatment did not alter cardiac DBH or rapid axonal transport of DBH in sciatic nerve. Blockade of alpha adrenergic receptors by administration of repeated doses of phenoxybenzamine resulted in elevated levels of plasma catecholamines, but produced no change in plasma DBH. Chronic reserpine treatment (2.5 mg/kg on alternate days) increased plasma DBH after 2 and 5 days, whereas vinblastine (3 mg/kg) caused a progressive fall in enzyme activity in plasma over the same time period. It is concluded that plasma DBH activity does not closely parallel adrenergic function and neurotransmitter release in the rat. The level of DBH in plasma appears to reflect the rate of enzyme synthesis and axonal transport, It is likely that mechanisms other than stimulation-coupled exocytotic release determine levels of DBH activity in plasma.


Inhibition of granulation tissue growth by histamine. Granulomas were induced in rats by subcutaneous implantation of formalin-soaked filter-paper disks. Daily subcutaneous injection of histamine at doses of two times 0.05 mg/kg and above inhibited the growth of granulation tissue as measured by a marked decrease in the dry-defatted granuloma weight and of the hydroxyproline and hexosamine content. Histological observations of granulation tissue indicated that histamine inhibited the proliferation of fibroblasts and the formation of capillaries. Inhibitory effects were also observed with the histamine releaser, sinomenine, and the histaminase inhibitor, aminoguanidine. These histamine effects seem not to be mediated by glucocorticoid release, since an effective dose level of histamine produced no change in growth or thymus weight. Prednisolone was less potent than histamine in inhibiting Prednisolone was ineffective at the dose tested. Subcutaneous injection of the H2-receptor antagonist, burimamide, blocked these histamine effects and also of sinomeinine and aminoguanidine. The H1-receptor antagonist, mepyramine, did not block these histamine effects. Burimamide alone enhanced the growth of granuloma. These results indicate that granulation-tissue growth in inflammation is affected by the inhibitory effect of endogenous histamine acting through H2-receptors.


Effect of cromolyn sodium and deuterium oxide on anaphylactic histamine release from rat peritoneal mast cells in vitro. Previous studies had shown that cromolyn sodium would inhibit anaphylactic histamine release from rat peritoneal mast cells in vitro (J. Pharmacol. Exp. Ther. 184: 41, 1973), under conditions where the maximum release was usually less than 30% of the total. In this report, deuterium oxide (D2O) is shown to potentiate anaphylactic histamine release from rat peritoneal mast cells in vitro. The cells were sensitized in vitro with rat reaginic antiovalbumin and challenged in vitro. The histamine was measured fluorometrically. At 37 degrees C the effect of D2O was concentration dependent with a 1.3-fold potentiation at 5% (v/v) and a 3-fold potentiation at 25% D2O (v/v). There was no effect of these levels of D2O on spontaneous histamine release. To be able to measure the rate of release, the sensitized cells were challenged with antigen at 25 degrees C in the presence and absence of D2O. Under these conditions, D2O increased both the rate of release and the total amount of release proportionately so that the T1/2 of release was not affected by D2O. The concentration of cromolyn sodium necessary to obtain 50% inhibition of histamine release increased from 6 muM in 0% D2O, to 80 muM in 10% D2O and to greater than 500 muM in 25% D2O. However, the lines showing the relationship between cromolyn sodium concentration and percent histamine released were not shifted in a parallel manner by D2O. This suggests that the interaction between D2O, cromolyn sodium and the histamine-releasing processes of mast cells is not a simple one.


On the role of mitochondria in transmitter release from motor nerve terminals. 1. The changes in transmitter release produced by mitochondrial inhibitors has been studied at the frog neuromuscular junction using conventional electrophysiological techniques for stimulation and intracellular recording. 2. Inhibitors of the electron transport chain and inhibitors of oxidative phosphorylation produce an increase in the frequency of appearance of the miniature end-plate potentials. This increase in frequency is observed also in calcium-free media. Mitochondrial inhibitors also augment the amount of transmitter liberated by a nerve impulse. 3. Ruthenium red, which is an inhibitor of calcium uptake by mitochondria, increases the spontaneous transmitter release but decreases the quantal content. The latter effect of Ruthenium red is antagonized by calcium. 4. The mitochondrial content of the motor nerve terminals is, on the average, 6.59%. 5. The experimental results are explained on the hypothesis that spontaneous release of transmitter reflects the resting level of intracellular free calcium and the evoked release reflects the sum of the resting calcium and the calcium brought in by the action potential. The mitochondria play a role in transmitter release by participating in the regulation of the intracellular free Ca.


Nuclear division in the ameboflagellate Adelphamoeba galeacystis. Nuclear division is synchronized cultures of the ameoboflagellate Adelphamoeba galecystis has been described. Division in this organism is typically promitotic. It occurs within an intact nuclear membrane and is characterized by the persistence of the nucleolus and its transformation into 2 polar masses. The nucleolus is stained with pyronin-Y by the methyl green pyronin-Y technic, and with Heidenhain's hematoxylin, but is unstained by the Feulgen reaction. The reaction with these stsins is removed after digestion of the nucleolus by ribonuclease. During mitosis the nucleolus undergoes an orderly series of vacuolizations before forming the polar masses. The chromatin is Feulgen positive, stains with methyl green by the methyl green pyronin-Y technic and undergoes a series of characteristic changes during the division process. Synchronizationof amebae grown on coverglasses was accomplished by transfer of cells from 30 to 38.5 C for a period of 100 min. A temporal sequence of nucleolar and chromatin participation in  the nuclear division of this organism is suggested.


[Ultrastructure of Sarcocystis tenella. I. Endozoïte (after negative staining)]. The employment of negative staining technics for the endozoites (cyst stages) of Sarcocystis tenella allowed the elucidation of certain aspects of their fine structure. The conoid consists of similar to 20 oblique fibers and is surmounted by a ring with regular ornamentation. In the conoid's interior there are 2 excentric parallel microtubules which extend posteriorly for a considerable distance into the adjacent cytoplasm. The fibers of the conoid, intraconoid microtubules, appear to have the same diameter and structure as the 22 subpellicular microtubules. They are "cemented" anteriorly into a periconoidal ring which surrounds the conoid. The "reticulated" pellicle has certain differentiations: the micropore, surrounded by a "fibrillar" element, similar to 10 subcircular structures arranged into an anterior crown, and 11 rows of granules converging toward the posterior end. The sarconemes look like rice grains which, contrary to previous statements, are independent of one another. It is established that there are only 2 rhoptries.


Toxicity of 4-nitroquinoline 1-oxide for Crithidia fasciculata. Growth inhibition of Crithidia fasciculata by 4-nitroquinoline 1-oxide (NQO) was observed in defined and complex media at 28 C. Aromatic amino acids, cystein, and nicotinic acid, among several other substances, were ineffective in overcoming NQO toxicity. Dicoumarol and bovine albumin reversed NQO inhibition. While bovine albumin probably acted by the extra-cellular binding of NQO, dicoumarol inhibited the activity of DT-diaphorase, which reduces NQO to 4-hydroxyaminonitroquinoline 1-oxide (HAQO). The DT-diaphorase from C. fasciculata had the same characteristics as the enzyme from rat liver. The specific protection by dicoumarol against NQO inhibition suggests that HAQO is the active toxic substance for C. fasciculata.


[Comparative effectiveness of pulmonary scintigraphy and radiography in detecting toxic side-effects of Bleomycin treatment (author's transl)]. Pulmonary toxic effects subsequent to intravenous injections of bleomycin in cancer therapy have well been demonstrated. In order to prevent the acute pathological pulmonary manifestations of the treatment, it is necessary that the patient be submitted to repeated controls of the lungs. As yet, the efficiency of the current diagnostic procedures for detecting the lesions dues to bleomycin injections is not clearly demonstrated. The authors present the results of a comparative study on the effectiveness of radiological and scintigraphic examination of the lung in detecting toxic side-effects of bleomycin. Both procedures were used repeatedly on rabbits, before, during and after the bleomycin treatment. The findings are discussed on the basis of the macroscopic and histological examination of the lungs. The results demonstrate that pulmonary scintigraphy with radioactive macroaggregates is more sensitive than radiography in detecting the early lesions of the lungs after bleomycin treatment.


The effect of oestrogen administered during the progestational phase of the cycle on transport of spermatozoa in ewes. Two split-plot factorial experiments are described, the first with 72 entire cyclic ewes and the second with 80. The pattern of transport of spermatozoa through the reproductive tract was studied, following treatments with progestagen and oestrogen or with oestrogen alone during 2 weeks preceding insemination. A daily dose of 25 mug oestradiol-17 beta administered to ewes for 14 days preceeding oestrus had a deleterious effect on the passage of spermatozoa through the cervix into the uterus within the first 2 hr after insemination. The numbers of spermatozoa recoverable from the cranial region of the cervix 2 hr after insemination appeared to be related to the numbers in the oviducts at 24 hr. These numbers were related to fertility data from an earlier experiment using similar treatments. The data for log numbers of spermatozoa recoverable from the cervix formed a near-normal distribution and so were suitable for formal statistical analysis. There was an interaction between progestagen and oestrogen influence before mating on the pattern of sperm transport through the cervix.


Xenotropic C-type viruses and autoimmune disease. New Zealand Black (NZB) mice develop a disease complex which resembles autoimmunity in man. Cells from both NZB embryos and adults spontaneously produce an infectious C-type virus which is xenotropic (X-tropic)-capable of being passed only to cells foreign to the host species. It differs from other endogenous murine C-type viruses which are ecotropic, i.e. infectious for cells of their home species. Xenotropic viruses are detected in embryos and adult tissues of other strains of mice but at less frequency and titer than in NZB mice. Moreover, natural anti-X-tropic virus neutralizing activity which is present in all mouse sera, is found in significantly higher titers in NZB mouse sera. A working hypothesis is that the X-tropic virus is an important agent for normal development and differentiation, but in NZB mice its increased expression results in autoimmune disease. Furthermore, its interaction with endogenous ecotropic virus leads to phenotypic mixing with possible enhancement of the immunologic disorders.


The heterogeneity of anti-DNA antibodies in systemic lupus erythematosus and other diseases. The antigenic specificities of antinucleic acid antibodies occurring in systemic lupus erythematosus (SLE), chronic active liver disease, and progressive systemic sclerosis (PSS) have been studied by means of haptenic nucleosides and nucleotides coupled to human serum albumin. SLE sera were also tested with dinucleotides. SLE and chronic active liver disease sera showed marked heterogeneity, producing precipitin lines with nucleosides or nucleotides, or both. The reaction might occur with a nucleoside and not with the corresponding nucleotide, or vice versa. The SLE sera reacted to dinucleotides with marked specificity, being able to recognize base sequences or to react with a dinucleotide despite the absence of a reaction with the individual bases. All sera from patients with PSS showed precipitins with RNA, uridine and UMP. PSS sera which reacted with a nucleoside also reacted with the corresponding nucleotide. Antibodies to DNA were found in a smaller proportion of PSS sera than in sera from SLE or chronic active liver disease. Their presence was confirmed by reactivity with thymidine and TMP.


Serologic abnormalities in spontaneous and drug-induced systemic lupus erythematosus. Extensive serologic changes occur in systemic lupus erythematosus (SLE) which are probably secondary to unknow primary cause(s). The New Zealand hybrid mouse model most likely has a viral-induced disease and does not show many of the clinical features of the human disease. The best example of human SLE which provides a clue to etiology is the drug-induced type, particularly that due to procainamide. In these patients it is possible to study the development of serologic changes prior to the onset of clinical manifestations, and then observe regression of the clinical and serological changes on withdrawal of the medication. Although there is a rough correlation between the many serologic abnormalities and the clinical picture, enough exceptions exist, so that single tests such as serum complement, anti-DNA antibodies, per cent DNA binding, and others, cannot be used as a sine qua non for management. Care of the patient still remains a clinical problem guided by various laboratory procedures but not dependent on any one. Alkyating agents have a limited role in the treatment of lupus nephropathy and cutaneous vasculitis but azathioprine is probably of no value in SLE.


A golgi study of the optic tectum of the tegu lizard, Tupinambis nigropunctatus. The dendritic patterns of cells in the optic tectum of the tegu lizard, Tupinambis nigropunctatus, were analyzed with the Ramon-Moliner modification of the Golgi-Cox technique. Cell types were compared with those described by other authors in the tectum of other reptiles; particular comparisons of our results were made with the description of cell types in the chameleon (Ramń, 1896), as the latter is the most complete analysis in the literature. The periventricular gray layers 3 and 5 consist primarily of two cell types--piriform or pyramidal shaped cells and horizontal cells. Cells in the medial portion of the tectum, in an area coextensive with the bilateral spinal projection zone, possess dendrites that extend across the midline. The latter  cells have either fusiform or pyramidal shaped somas. The central white zone, layer 6, contains fibers, large fusiform or pyramidal shaped cells, fusiform cells, and small horizontal cells. The central gray zone, layer 7, is composed predominately of fusiform cells which have dendrites extending to the superficial optic layers, large polygonal cells, and horizontal cells. The superficial gray and white layers, layers 8-13, contain polygonal, fusiform, stellate, and horizontal elements. Layer 14 is composed solely of afferent optic tract fibers. Several differences in the occurrence and distribution of cell types between the tegu and the other reptiles studied are noted. Additionally, the laminar distribution of retinal, tectotectal, telencephalic, and spinal projections in the tegutectum can be related to the distribution of cell types, and those cells which may be postsynaptic to specific inputs can be identified. The highly differentiated laminar structure of the reptilian optic tectum, both in regard to cell type and to afferent and efferent connections, may serve as a model for studying some functional properties of lamination common to cortical structures.


[Unusual complications of prostatectomy (author's transl)]. The authors report a case of cystitis with incrustation of the trigone which required re-implantation of the ureters. The operation suggested that when the hemostatic balloon is inflated excessively, this may harmful.


Mitosis is required for production of murine leukemia virus and structural proteins during de novo infection. Cloned 3T3FL cells were synchronized in G1 phase of the cell cycle by deprivation of multiplication stimulatory activity of serum and were then infected with Moloney leukemia virus. Eclipse period of virus could be made to vary from less than 10 to 34 h. All virus release was completely dependent and occurred immediately after the first mitosis following serum reconstitution. Virus yield was not affected by the time of virus inoculation as related to the cell DNA synthetic phase. Colchicine arrested the cells in mitosis and prevented the formation of infectious virus. Viral proteins p10, p30, and gp71 were assayed in cell lysates during the growth curve of virus in synchronized cells. The group-specific determinants of each protein were measured in a competition radioimmunoassay. None of the virus proteins appeared during the eclipse period of the virus. All three proteins appeared simultaneously,  coincident with mitosis, and continued to rise during the G1 phase. The absolute quantities of each protein were proportional to the amount of Moloney leukemia virus produced. The relative amounts of some of the viral proteins in the cell did not correspond to their content in purified virions suggesting several possible mechanisms of control.


The assessment of results following endocrine therapy for prostatic cancer. Generally, recent reports on the side effects of estrogen therapy for prostatic cancer have concerned mortality statistics, relatively little attention having been paid to the quality of life of individual patients. We herein propose an assessment of treatment regimens based on the concept of the time during which a patient remains free of tumor progression or serious side effects. A particular regimen has been examined in relation to the hormonal effects of endocrine ablation, and to the dosage and type of estrogen therapy used in 59 men with prostatic cancer. Although no significant difference among treatment methods has emerged in this small group (except for the more frequent occurrence of fluid retention with the stilbestrol dosage, 30 versus 15 mg. per day) and no correlation between the degree of testosterone suppression and length of remission has emerged so far, this method of assessment proved useful and should be applicable widely. It was confirmed that gonadotropin levels remained in the normal range in patients whose testosterone levels were suppressed with chlorotrianisene.


Antigenic analyses of Lactobacillus fermenti. Antigenic analyses of Lactobacillus fermenti were carried out by double immunodiffusion in agar using extracts prepared with cold trichloroacetic acid (TCA) or hot dilute hydrochloric acid (HCL). A common antigen of L. fermenti, designated as antigen f by the author, was extracted from whole cells with dilute HCL, but not with TCA. The antigen f was also observed in Lactobacillus casei. In addition, all strains isolated from human saliva contained antigen 6 in their cell walls, while the antigen was not observed in most of the isolates from human feces. Therefore, L. fermenti could be divided into two subgroups based upon the existence of antigen 6. Antigen 7 which was demonstrated in some strains of L. fementi was shared by other species of lactobacilli belonging to the serological groups D and E. The common antigen 3 found in lactobacilli was extracted from all strains of L. fermenti Sugar components of cell walls were mainly galactose, glucose and glucosamine (including N-acetylglucosamine), but a small amount of rhamnose was present in the cell wall of only one strain. Inhibition tests with various sugars showed that the serologically active sugars were galactose for antigen f and glucose for antigen 6.


The skin-reactive antigens of Mycoplasma pneumoniae. Guinea pigs experimentally infected with Mycoplasma pneumoniae or immunized with the orgnaism in combination with Freund's complete adjuvant developed a delayed hypersensitive skin reaction following on intradermal injection of the M. pneumoniae antigen. The amount of protein necessary to produce the delayed skin reaction was as low as 0.01 mug. When the sonicated whole cells were extracted with aqueous acetone, the delayed skin reactivity was found mostly in the acetone insoluble (lipid-depleted) fraction. On the other hand, the lipid fraction which was isolated by a chloroform-methanol extraction of the acetone-soluble fraction and had a high titer of complement-fixing activity, exhibited little delayed skin reactivity. The lipid-depleted antigens as the whole cell antigens produced delayed skin reactivities in human patients.


Long-time observations on the Blalock-Taussig operation VIII. 20 to 28 year follow-up on patients with a tetralogy of Fallot. This study extends our previous observation on patients with a tetralogy of Fallot, operated on by the late Dr; Alfred Blalock and his associates between 1945 and 1951, from a 15 year follow-up to 20 years and assesses the final status of these patients 20 to 28 years after their first operation. This study is mainly concerned with the 432 patients known to be alive at the beginning of the 15th postoperative year. At the beginning of the 20th year, 376 patients were alive, 24 had died, 32 had been lost to follow-up. Review of the final status of those 432 patients showed that 169 had no further cardiac surgery after their initial operation, 36 had further palliative surgery, and 227 had total correction. Thirty-seven percent of the first group, and 79.3% of those with total correction were doing well. These two groups, however, are not comparable. Approximately 250 patients have married; 161 have one or more children. Thirty-five percent have graduated from college and 68.7% are earning substantial incomes. The high scholastic achievement of many of these patients is strong evidence that low oxygen saturation of arterial blood is not a prime cause of mental retardation. The occupations of the patients indicate that the quality of their lives is extremely good and that a cardiac handicap in childhood does not preclude success in adult life. Approximately 69% of these patients have repaid in taxes the cost to society of their rehabilitation.


Reduced monocyte phagocytosis in patients with advanced Hodgkin's disease and lymphosarcoma. The monocytes of 7 patients with advanced Hdgkin's disease (stages III and IV) and of two patients with generalized lymphosarcoma exhibited a highly significant impairment of the phagocytosis of IgG-coated red cells, regardless of receiving therapy or not.  In contrast three patients with M. Hodgkin, stage II B, and one with lymphosarcoma in complete remission showed a rather elevated monocyte phagocytic acitivity.  The nitroblue tetrazolium reduction by monocytes in the mean was significantly enhanced in all patients investigated, compared with normal persons, although only in one patient a bacterial infection was apparent at the time of the test.  The possible implication of the findings in the well known immunodeficiency present in M. Hodgkin and lymphosarcoma is discussed.


Studies on modification on the cellular response to injury. Extracellular acidosis (pH 6.6) has been found to delay the lethal effect of p-chloromercuribenzene sulfonic acid on Ehrlich ascites tumor cells. At pH 6.6, 50 per cent of the cells died within approximately 80 minutes, compared with approximately 10 minutes at pH 7.5 or approximately 5 minutes at pH 8.0. It was also observed that low pH produced a dissociation between potassium loss, ATP levels, cell volume, and cell death. The possible mechanism of this effect is discussed; it is our hypothesis that it involves proton interactions with plasma membrane components which either affect available membrane sulfhydryl groups or otherwise stabilize the cell membrane against loss of semipermeable characteristics and cellular lysis.


Effects of the cholesterol biosynthesis inhibitor ay9944 on organotypic cultures ofmouse spinal cord. Retarded myelinogenesis and induction of cytoplasmic inclusions. Young cultures of fetal mouse spinal cord were exposed to nutrient medium containingAY9944 [trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride], apotent cholesterol biosynthesis inhibitor, and their reactions were studied by light and electron microscopy.  AY9944 treatment for 4 to 7 days retarded cultures revealed anaccumulation of numerous intracytoplasmic inclusions in perikarya of neurons, astrocytes,and oligodendrocytes.  These inclusions were also found in dendritic processes, myelinated axons, and presynaptic terminals.  These inclusions were composed of concentric lamellar structures or of reticular internal structures.  Although considerable improvement of myelination and diminution of cytoplasmic inclusions were noted following the removal of the inhibitor and the restitution in normal nutrient medium, a complete recovery oflesions was not observed during the 3-week restitution period in vitro.


Hepatocellar hyalin (Mallory bodies) in long term griseofulvin-treated mice: a new experimental model for the study of hyalin formation. Experimental studies on the significance and origin of hepatocellular "alcoholic" hyalin (Mallory bodies) are hampered by the lack of a suitable animal model. In the present paper, the experimental production of hepatocellular hyalin identical with human alcoholic hyalin both light and electron microscopically in long term griseofulvin-treated mice is described. Moreover, the results conclusively disprove the specificity of Mallory alcoholic hyalin for alcohol-induced liver cell damage.


Adenocarcinoma of the lung: clinicopathological study. A review of our 247 patients with adenocarcinoma of the lung revealed the overall five year survival rate to be only 0.81%. Lung resection offers the chance of cure if the lesion is peripherally located and without lymph node involvement. Direct chest wall invasion by tumor is not contraindication to surgery. Radiation therapy was not especially effective in our series. Several chemotherapeutic agents gave an overall response of 31.1%.


Complete atrioventricular canal associated with tetralogy of Fallot: clinical experience and operative methods. Data on 8 children with the combined anomalies of complete atrioventricular canal and tetralogy of Fallot are presented. Six of the children had only a palliative procedure, and only 1 of these patients is doing relatively well at the present time from a clinical standpoint. Two of the remaining 5 children undergoing palliative procedures have not been helped significantly, and 3 of the children in this group subsequently died. Two children have had an attempted total correction of this complicated intracardiac problem. One of these children, in whom the diagnosis of atrioventricular canal was not made preoperatively, died in the early postoperative period. In the other child, the correct diagnosis was made preoperatively, and a satisfactory, totally corrective procedure was achieved. The patient is asymptomatic at this time.


Influence of oestrogen on experimental pyelonephritis caused by Escherichia coli. Strains of Escherichia coli isolated from patients with suspected pyelonephritis had a strong predilection for growth in kidney tissue. Viable bacterial counts in experimentally infected mice showed that after 96 hours approximately 98% of the total-body count was found in the kidney. Strains of E. coli isolated from cases of gastroenteritis in man and animals had little or no tendency to grow in the kidney. Treatment of male and female mice with oestrogen significantly enhanced the growth of "pyelonephritic" strains in the kidney, but had no effect of any kind on the growth of "gastroenteritis" strains. These preliminary results suggest that oestrogen may predispose to the development of kidney infection in the female and that there is an important link with the virulence of the E. coli concerned. Only those strains that have a natural predilection for growth in the kidney are likely to be influenced  by oestrogen.


A controlled clinical trial of machine perfusion of cadaveric donor renal allografts. Outcome in eighty-eight recipients of cadaveric donor renal allografts preserved before implantation by machine perfusion with a solution of human albumin was compared to that for eighty-three recipients of similar kidneys implanted after simple cold storage. Average total ischaemic intervals for machine-perfused and cold-stored kidneys were 18 and 4 1/4 hours, respectively. Machine-perfused kidneys were implanted regardless of perfusion characteristics. Initial function and 1-month and 1-year graft survivals for the machine-perfused group (58%, 85%, 68%, respectively) were either similar or improved compared to those of cold-stored kidneys (58%, 81%, 52%, respectively). Improved 1-year survival for machine-perfused grafts was dependent upon reduced rejection. Careful donor selection and management ensured good machine perfusion of kidneys on 90% of occasions. In the other 10%, despite poor perfusion characteristics, outcome for kidneys was similar to those with good perfusion characteristics. Antilymphocyte globulin treatment reduced rejection whether allografts were machine perfused or not. In the absence of antilymphocyte globulin treatment, machine-perfused kidneys did much better than cold-stored kidneys. Machine perfusion had important advantages and improved the results in kidney-graft recipients.


Passovoy factor: A hitherto unrecognised factor necessary for haemostasis. A moderate bleeding diathesis transmitted as an autosomal dominant was found in five members of four generations of the same family. The affected patients had prolonged partial thromboplastin-times and normal levels of all the known clotting-factors. The haemorrhagic diathesis was attributed to a deficiency of a hitherto unrecognised coagulation factor--i.e., the Passovoy facto.


Age-related refractoriness of PHA-induced lymphocyte transformation. II. 125-I-PHA binding to spleen cells from young and old mice. Using 125-I-labelled red kidney bean phytohemagglutinin (125-I-PHA), we have found that spleen cells from old BC3F1 mice bind this plant mitogen equally well, if not better, than spleen cells from young BC3F1 mice, although PHA-induced blastogenesis of spleen cells from old mice is sharply reduced. Analyes demonstrated that there is neither significant alteration of binding affinity nor decreased total number of membrane receptor sites for PHA in senescing mouse spleen cells. The amount of PHA which was initially bound to spleen cells in serum-free medium appeared to be insufficient for a subsequent full stimulation of blastogenesis ([3-H]thymidine incorporation) in either young or old mouse spleen cells; when washed free of unbound extracellular PHA and upon clutivation in serum-containing culture medium, spleen cells rapidly released more than 90% of the bound PHA. Also, temperatures which change cell membrane morphology played a significant role in the binding and retention of PHA. However, no difference was observed between young and old mouse spleen cells in all these phenomena of PHA-cell membrane interaction.


Rauwolfia derivatives and breast cancer. A case/control study in Olmsted County, Minnesota. In response to three reports of an association between rauwolfia derivatives and breast cancer, a case/control study was undertaken in Olmsted County, Minnesota. Comparison of a cohort of women with breast cancer to an age-match cohort of women with cholelithiasis failed to show any meaningful differences in the two groups except with respect to a history of hypertension. The rates of use of rauwolfia derivatives by hypertensive cases and controls were identical--which, along with other considerations, leads to the conclusion that an association between the use of rauwolfia derivatives and breast cancer is unlikely.


Matched-pairs study of reserpine use and breast cancer. This paper reports on an analysis of psychiatric population. 55 female patients with breast cancer were matched with non-cancer patients on age, year of admission, psychiatric diagnosis, race, and religion. Reserpine use was examined for yearly use by each year preceding the diagnosis of breast cancer, by cumulative yearly use, and by other defined time periods. Regardless of the definition of reserpine user, there were no significant increased relative risks of breast cancer for those women on reserpine. There was a fairly low proportion of patients from each group who were on the drug in any given year, and a fairly wide range of total dosage received. Over half of the women used reserpine at some time during their hospital stay.


25-Hydroxycholecaliferol and fractures of the proximal. Plasma 25-hydroxycholecalciferol (25-H.C.C.) has been measured in 67 consective cases of fracture of the proximal femur. The values found in these patients were not different from values found in these patients were not different from those in control groups at the same time of the year. Plasma 25-H.C.C. was not correlated to plasma calcium or phosphorus, the Ca times P product, or the alkaline phosphatase. X-rays showed Looser zones in only 1 patient, in whom the lowest plasma 25-H.C.C. was found. Osteomalacia is not uncommon among elderly people in Denmark, but it is more likely to depend on a decline in the renal efficiency to convert 25-H.C.C. to 1,25-dihydroxycholecalciferol than a low dietary intake of vitamin D.


Retroperitoneal fibrosis during treatment with methydopa. Retroperitoneeal fibrosis (R.P.F.) and a positive direct Coombs test developed in a patient who had received 1.4 kg. of alpha-methyldopa over a period of 5 years. Immunofluorescence microscopy demonstrated deposits of IgG, IgM, and IgA on the collagen fibres of the R.P.F. Biopsy speciments of the temporal artery, the right kidney, and the R.P.F. did not show signs of general arterial disease on light, immunofluorescence, and electron microscopy. Drugs which provoke autoimmunisation and interfere with nervous transmission are known to induce deposition of collagen or R.P.F. This suggests that R.P.F. in this patient was probably caused by alpha-methydopa.


Role of HBs Ab in development of hepatitis. 24% of a healthy control population had antibody to hepatitis-B surface antigen (HBsAb) detectable by passive haemagglutination. The frequency was higher in other population groups in proportion to the intensity of contract with individuals or material positive for HBsAg. Data obtained during an outbreak of type-B hepatitis indicate that immunity to the disease is directly dependent on the titre of circulating HBsAb. A close relationship was found between the presence of HBsAb and liver dysfunction in carriers of HBsAg. This supports the hypothesis that immune response to the antigen may be necessary for the development of liver damage in type-B hepatitis. Nevertheless, since a good antibody response to HBsAg was found in uraemic patients, in whom hepatitis had a clinical course quite different from the population at large, it is thought that immune mechanisms other than the humoral response may account for the pathogenesis of the disease.


Increased sensitivity of platelets to adrenaline in human myotonic dystrophy. Platelets from patients with myotonic dystrophy showed a normal pattern of aggregation in response to adenosine diphosphate (A.D.P.) and collagen but were unusually sensitive to adrenaline, aggregation being detectable with adrenaline concentrations as low as 0.041 mumol per litre. In other diseases in which such sensitivity has been reported this has been accompanied by a similarly altered response to A.D.P. The increased platelet aggregation could be due to increased uptake of Ca++ by platelets or to a decrease in phosphorylation of the platelet membrane.


Ill-health and child abuse.

Ill-health and child abuse. Intensive therapeutic work with families, in which child abuse had occurred, suggested that bonding failure related in part to the pregnancy, perinatal experience, and early ill-health of the abused proband and parents. 25 consecutive unequivocally abused children who had 1 or more siblings were selected from our referrals. Six factors emerged as highly significantly over-represented in the proband biography as compared with the control sibling group: abnormal pregnancy, abnormal labour or delivery, neonatal separation, other separation in the first six months, illnesses in the first year of life, and illness in the mother in first year of life. These data suggest that treatment of parents during pregnancy the perinatal period, and early infancy may well be fruitful in the prevention of child abuse.


Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men. The feminization frequently observed in men with alcoholic liver disease has not been satisfactorily explained by existing reports. We have measured plasma estrone, prolactin, estrogen-stimulated neuorphysin, and sex steroid-binding globulin concentrations in 50 men with chronic alcoholism and varying degrees of alcoholic liver disease in an effort to further elucidate possible hormonal mechanisms responsible for the observed feminization. Plasma concentrations of each of these parameters were at least two-fold elevated (p smaller than or equal to 0.01) when compared to values obtained for the same steroid or protein in plasma obtained from normal men. The plasma concentrations of estrone and prolactin in men studied with synecomastia were significantly greater (p smaller than or equal to 0.01 and p smaller than or equal to 0.05, respectively) than were the concentrations of these two hormones in those without this physical sign. Similarly, those men with spider angiomata had significantly greater (p smaller than or equal to 0.01) plasma estrone levels than did the men without this cutaneous vascular abnormality. These significant hormone elevations may contribute to the pathogenesis of feminization so frequently observed in chronic alcoholic men.


[Fine needle aspiration biopsy of abdominal and retroperitoneal tumours under ultasonic guidance (author's transl)]. In 94 patients with tumours of the abdomen or the retroperitoneal space detected by ultrasonography fine needle aspiration puncture was performed under ultrasonic control. The aspirated material was stained with Pappenheim's solution for cytological examination. In 86 patients the diagnosis was definitely established. Of 49 patients with malignant growths (liver 35, kidney 9, colon 2, subcutaneous tissue 2, pancreas 1) tumour cells were gained in 40. In 4 other pathients the cytological findings were suspicious of malignancy. In 37 patients with benign processes (liver 35, subcutaneous tissue 2) no false-positive diagnosis was made. Complications induced by the puncture, especially hemorrhage were not encountered. The combined ultrasonic-cytological examination is simple, fast, almost riskless and well-tolerated. It allows to avoid other more expensive methods to obtain tumour material which usually carry some risk. It is especially valuable as a screening method for malignant growth in the abdominal cavity and the retroperitoneum.


[The so-called inoperable rectal carcinoma. Simultaneously, a contribution to the prognosis of rectal carcinoma]. Rectal cancer is quite easy to identify. Simple methods of investigations and early symptoms should allow a good prognosis. This is patholphysiologically supported by slow increasement and relatively late filialisation along long metastatic roads. Therefore it is to be regretted, that of 632 patients, suffering from rectal cancer in the years 1955-1970, 179 (28,3%) could not be treated on cure. Even palliative procedures had a postoperative mortality of 24,6%. This delay in early diagnose reduced the time of survival from 72% 2-jears-survival, when operated on cure (see article) to 59,1% (see article), respectively from 52,1% 5-years-survival (see article) to 38,5% (see article). These results can be only improved by regular prophylactic examinations.


The induction of chromatid deletions in accord with the breakage-and-reunion hypothesis. In the present experiments it has been possible to study large numbers of X-ray induced chromatid deletions, or breads, in Chinese hamster chromosomes and to discern whether or not a sister chromatid exchange also occurs at the point of breadage. Chromatid deletions are only infrequently associated with a sister chromatid exchange. This is contrary to the expectations derived from the exchange hypothesis of Revell. Pn the basis of this hypothesis, in which chromatid deletions are considered to be incomplete exchanges that occur in the necks of little loops in the chromosomes, 40% of the chromatid breaks are expected to be associated with sister chromatid exchanges. The present data are in accord with the conclusions drawn from the earlier autoradiographic experiments of HEDDLE AND BODYCOTE, and show that chromatide breaks can be accounted for on the basis of the breakage-and reunion hypothesis, with the majority being simple breaks and some being incomplete exchanges between two such breaks.


[Identification of metabolites and metabolism of hexachlorobenzene in a mold culture]. Hexachlorobenzene is but slowly metabolized by a lindane-decomposing mould culture, only pentachlorobenzene being detected as a metabolite. The degradation of pentachlorobenzene yields the following metabolites: pentachlorophenol, 2,3,4,5-tetrachlorophenol, 2,3,4,6-tetrachlorophenol, 1,2,3,4-tetrachlorobenzene, 1,2,4,5- and/or 1,2,3,5-tetrachlorobenzene, 2,3,4-trichlorophenol, 2,4,6-trichlorophenol, 3,4,5-trichlorophenol, 1,3,5-trichlorobenzene. The establishment of a degradation pattern is under way.


Possible association of oncornavirus type D with some forms of human cancer. The method of molecular hybridization of nucleic acids of oncornavirus type D produced by HEp2 cells with cellular nucleic acids was applied. No sequences homologous to the viral nucleic acids were found in normal human embryo cells as well as in bovine, porcine, murine, and chicken cells. No such sequences were found in tissues of malignant lymphomas. Sequences homologous to the viral nucleic acids were found in some cancer cells, predominantly in hormone-associated tumors of females.


Molecular hybridization study of cells producing oncornaviruses type D. Five human cell lines producing oncornaviruses type D were studied by the method of molecular hybridization of viral and cellular nucleic acids. Repeated sequences of viral genome equivalents were found in nuclear DNA and numerous copies of viral genome were found in the cytoplasm. The viruses produced by the cell lines were found to be identical or closely related as regards nucleotide sequences of their genomes.


Visceral radioisotopic lymphography of the testicle. Scintigraphic studies made in 75 patients, respectively on 130 testicles with the aid of the organ radio-isotopic lymphography enabled to determine more exactly the location and the variety of the testicular lymph centers. It should be pointed out that in 58.5% of the patients the lymph centers are situated on the left of the middle line and only in 6.1% on the right. In some cases iliac lymph nodes were demonstrable. Attempts were made to use this method in investigation of the patients with malignant tumours of the testicles.


[Serum neuraminic acid level in patients with cerebrovascular disorders]. The authors determined the level of neuraminic acid in the serum of 50 patients with encephalomalacia and 25 patients with cerebral haemorrhages on the 1st, 3d and 7th days of the disease. Twenty healthy subjects served as controls. A statistically significant rise in the concentration of this substance was observed in both groups of patients throughout the whole period of observations.


The peripheral odontogenic fibroma.

The peripheral odontogenic fibroma. An extensive review of the English-language literature has produced only five undoubted cases of peripheral odontogenic fibroma. This article reports ten new cases. The age and sex of the patients and the distribution by site and histology of the lesions are compared with those of other cases of bifrous tumors and neoplasms of odontogenic origin. It is postulated that this lesion may be more closely related to the fibrous euplis than was previously realized. Both lesions show hyperplasia of the basal layer of the covering ipithelium into double strands resembling odontogenic epithelium. It is suggested that this hyperplasia may be related to induction of the covering epithelium by primitive ectomesenchymal remnants within the gingivae. Proliveration of odontogenic rests within the peripheral odontogenic frbroma may be related to the same stimulus.


Antigenic relationships between Candida albicans and various yeasts as reflected by immunoglobulin-class specificity. A group of guinea pigs was inoculated into the foot pads with a single dose of Candida albicans in complete Freund's adjuvant, while another group was similarly inoculated once in the foot pads but also several times intramuscularly, with Candida alone. All guinea pigs were bled at different intervals after immunization and sera were separated chromatographically into IgG and IgM fractions. In order to study the antigenic relationships as reflected by immunoglobulin-class specificity, IgG and IgM fractions and whole sera obtained from guinea pigs differently immunized, were tested for the presence of agglutinins against C. albicans, six other species of Candida, and species of the ascosporogenous genera Saccharomyces, Kluyveromyces and Schizosaccharomyces. The results show that (1) only IgG fractions of the different sera prepared contained the specific anti-C. albicans antibodies; (2) IgG and IgM fractions of the sera obtained from a single inoculation did not reveal a specific pattern expressing antigenic relationships of the yeast studied, and (3) the IgM fractions of the sera obtained from several inoculations had a more homogenous pattern of reactivity, since mainly these contained the agglutinins against the ascosporogenous yeast species.


[Ligation of the hepatic artery for metastases from a carcinoid tumor]. Following ligature of the hepatic artery in the treatment of hepatic metastases of a carcinoid tumour of the small bowel, the authors noted  a spectacular regression in functional symptoms. Several similar cases are recorded  in the literature and similar findings given. The comfort, even though short-lived, which ligation brings justifies its use.


Hybridization of pigeon globin messenger RNA with complementary DNA synthesized in vitro by reverse transcription: influence of the homopolymeric regions. The kinetics of hybridization of pigeon globin messenger RNA with complementary cDNA synthesized by means of AMV reverse transcriptase is complex. Addition of poly A or poly U in excess to the reaction mixture normalized the kinetics. It is concluded that association of the complementary homopolymeric regions of mRNA and cDNA accelerates the complex formation between heteropolymeric sequences in a fraction of the molecules.


Fractionation of protein mixtures through differential adsorption on a gradient of substituted agaroses of increasing hydrophobicity. Data are presented which indicate the feasibility of protein fractionation at high salt concentrations (greater than or equal to 3 M NaLl) through differential hydrophobic (non-ionic) adsorption on a series of columns of agaroses substituted with ligands of increasing hydrophobicity. By means of such a hydrophobicity gradient of connected columns, separation of mixtures of gamma-globulin and serum albumin, as well as group separation of proteins in dialyzed human blood serum, has been achieved.


The neuraminidase yield-reduction bioassay of human other interferons. The production of neuraminidase by the recombinant influenza virus X7(F1) in human monkey, rabbit, hamster, mouse, and chicken cell cultures is inhibited by interferon. Described is a new enzyme assay for neuraminidase that can be applied to the bioassay of interferons. The advantages of this interferon bioassay are its sensitivity, reproducibility, rapidity, and convenience.


Biochemical effects of bleomycin A2 on Novikoff hepatoma ascites cells. Purified nucleolar DNA was markedly degraded at a concentration of 13 mug/ml by bleomycin A2; bleomycin concentrations 20-30 times greater were required to degrade nucleoplasmic DNA. Whole nuclear DNA was degraded to only a small extent at 13 mug/ml but was markedly degraded at higher bleomycin concentrations. Treatment of the various types of DNA with high concentrations of bleomycin A2 produced low molecular weight (approximately 6S) fragments that were no longer sensitive to degradation by bleomycin A2. Hybridization studies demonstrated a loss of ribosomal DNA sequences from nucleolar DNA treated with bleomycin A2 in vitro. Studies on RNA synthesis in Novikoff hepatoma ascites cells in vitro showed there was a decreased uptake of 32Pi into high molecular weight nuclear RNA in the presence of bleomycin A2. These results indicate that nucleolar function is inhibited by a direct effect of bleomycin A2 on nucleolar DNA.


Posttranslational protein modifications, with special attention to collagen and elastin. It is apparent that significant progress has been made in our understanding of the biosynthesis, modifications, and maturation of collagen and elastin. We now recognize and partially understand special reactions involved in hydroxylations within the cell and complex cross-linking processes occurring outside the cell. Recent experiments (191) have shown that in human diploid fibroblast cultures of limited doubling potential (191) the hydroxylation of collagen prolyl residues appears to be "age" or passage-level dependent. With increasing passage level of these cultures, both the ascorbate requirements and the extent of collagen hydroxylation decrease. "Young" cell cultures have a strong requirement for complete hydroxylation and without ascorbate there is only about 50% of the normal level. "Middle-aged" cultures show higher hydroxylation without and full hydroxylation with ascorbate, whereas "old" (or cultures close to "senescence") are incapable of full hydroxylation with or without ascorbic acid. Although the overall system may show some deterioration with increasing passage levels, it appears that with increasing passage levels other components in the cell replace the ascorbate dependence of the hydroxylase system to a greater exten. In some ways, aging WI-38 cultures begin to resemble some transformed cells in their biochemical reactions, although they continue to remain diploid and eventually lose the ability to replicate. It is not yet known whether old animals can produce collagen, which may now be underhydroxylated, perhaps contributing to certain senescent changes. Careful examination of the hydroxylation index of collagen produced in organoid cultures of tissue biopsies as a function of donor age might be informative, particularly if one looks at the quality of collagen by employing collagenase and other proteolytic digests with collagen (191). One could comare the levels of frequent and characteristic peptide triplet sequences such as Gly-Pro-Hyp to Gly-Pro-Pro, Gly-Ala-Hyp to Gly-Ala-Pro, or Gly-Pro-Hyl to Gly-Pro-Lys and others for evaluation of hydroxylation throughout the entire molecule or at selected sequences.


Secretory and structural changes in the parotid salivary gland of sheep and lambs after parasympathetic denervation. The effect of the parasympathetic nerve supply on the development of the parotid gland in the immature lamb and its maintenance in the adult sheep has been investigated by unilateral postganglionic denervation. Seventy-seven to ninety-three days after denervation secretory activity of the gland was examined and material taken for histological examination. The adult denervated glands secreted at lower rates than the innervated and their atropine-resistant secretory flow was reduced to as low as one fifth of that of the innervated glands. In two lambs an atropine-resistant flow did not develop in the denervated glands: in another two, flows of saliva from the denervated glands were present but were much less than in the contralateral innervated glands. After denervation glands were, with one exception, smaller than the contralateral innervated glands. The acinar cells of the denervated adult and lamb glands were smaller than the cells of the innervated glands but similar in size to those of 7-14 day old unoperated control lambs. Acinar cells in denervated glands had periodic acid Schiff staining material but the staining reaction to pyronin-methyl green was similar in the innervated and denervated. The results indicate that the integrity of the parasympathetic innervation is essential for the development of the parotid gland of the sheep and for its maintenance in the adult animal.


Hepatic complications of antituberculous therapy. Drug hepatitis occurred in 0-32 per cent of 7492 patients receiving antituberculous therapy, while the overall incidence of drug reactions was estimated at 9 per cent. PAS was the most common cause of drug hepatitis among the 38 patients analysed. The clinical, biochemical and haematological picture of antituberculous drug hepatitis was found to be fairly uniform. However, the patients with definite PAS hepatitis had lower SGOT values than those in whom there was uncertainty whether PAS or INH was implicated. Premonitory symptoms were present in all but four patients before the onset of jaundice. One or more of the features associated with dry hypersensitivity reactions, such as fever, rashes, lymphadenopathy, arthralgia, leucocytosis, eosinophilia and atypical monocytes were present in 89 per cent of cases so that confusion with viral hepatitis seldom arose. Sensitization time was less than three months in all except three patients, who were considered to be suffering from viral hepatitis. While no patients with PAS hepatitis died, the overall mortality was 17 per cent. A review of the literature stresses the frequency of asymptomatic elevations of SGOT, the value of clinical surveillance during the early months of therapy and the importance of stopping all therapy immediately warning symptoms appear.


[Tubular proteinuria (electrophoretic studies and properties of the microglobulins)]. The electrophoretic study of tubular proteinuria, carried out on the acrylamide-agarose electrophoresis, shows various patterns of tubular proteinuria characterized by low molecular weight proteins: alpha2-microglobulin, beta2-microglobulin and post gamma. The immunoprotidologic study of the microglobulins is difficult since they have a similar molecular weight. The zonal acrylamide-agarose electrophoresis allows the isolation of beta2m and post gamma. Recent studies suggest a number of hypothesis on the function of the microglobulins.


[Methods of qualitative detection of proteinuria in mass surveys]. In a survey of the qualitative methods of research into proteinuria, the Authors recall, apart from later modifications, the old techniques based on the occurrence of turbidity from precipitation of proteins obtained with heat and/or by the use of various anionic reagents. Particular attention is given to the rapid tests with paper strip based on the phenomenon of error made by indicators in the presence of protein solutions. Their sensitivity, their specificity and above all the fact that their use is unbeatably practical are discussed, both on the basis of data derived from other studies and on the basis of various personal observations. From the latter, the Authors deduce and demonstrate the substantial constancy in the behaviour of various types of paper strip test, even those produced in different periods and by different manufacturers; how the data obtained with these various papers can be compared with the best modern methods of measuring turbidity; and the different sensitivities of the papers with various types of proteins such as albumins, globulins and in particular immunoglobulinic micromolecular fragments. Finally, they show that falsely positive reactions in alkaline urines because of ammoniacal fermentation cannot be ascribed to the increase of pH, but rather directly to an excess of ammonium ions. After having remarked that tests with paper strip have to a large extent taken the place of classical methods, more for obvious reasons of expediency than for any real qualitative superiority, the Authors maintain that it is advisable, though only in border-line cases, to make a routine check with one of the traditional methods in order to screen genuine cases of proteinuria.


[Determination of urinary total proteins and some protein fractions]. In unconcentrated specimens measurements have been made of total proteins, by DOETSCH gel-filtration method, and of albumin, transferrin and of alpha-2-macroglobulin, by LAURELL electroimmunodiffusion technique. The results confirm that the gel-filtration method provides specific, reliable measurement of proteins in amount as little as 50 mg/1. The proteinuria of 21 samples of urine has been determined by the DOETSCH method and by the biuret method after protein precipitation by perchloric, trichloracetic and phosphotungstic acid. Only the use of phosphotungstic acid as precipitant provides a good correlation of results between the biuret method and the direct gel-filtration-biuret method. LAURELL electroimmunodiffusion technique was improved to allow the determination of 5 mg/1 of albumin, and transferrin, and of 1 mg/1 of alpha-2-macroglobulin. The AA. emphasize the advantages of using sensitive methods which do not require the preliminary concentration of the sample, for the analysis of urinary proteins.


Evaluation of rapid radiation treatment schedules utilizing two treatment sessions per day. The authors studied normal human skin reactions to two different rapid radiotherapy schedules of 2 sessions per day and evaluated their effectiveness in relief of pain and local tumor control. Patients were randomized to three treatment groups: SCHEDULE A (control): conventional one treatment per day regimen totalling 3,760 rads in 22-23 days; SCHEDULE B: 2 sessions per day totalling 3,440 rads in 10-11 days; and SCHEDULE C: 2 sessions per day totalling 3,568 rads in 10-11 days. The pattern and magnitude of skin reactions in the three schedules are nearly identical but tumor regression and pain relief were achieved faster in the rapid fractionation schedules.


Inability of Ni++ and Co++ to release histamine from rat peritoneal mast cells. Ni++ and Co++ concentrations from 10 minus 3M to 10 minus 6M were added to rat peritoneal mast cells. These metal ions, at the concentrations indicated, did not cause histamine release from the mast cells, and did not inhibit the histamine release mediated by compound 48/80. On the basis of these studies, anaphylactoid edema of the rat following injection of i++ or Co++ is on a basis other than a direct effect of the m-tal ion on mast cells.


Differential inhibition of rat liver sialyltransferase(s) by various aflatoxins and their metabolites. Sialyltransferase(s) activity [CMP-N-acetylneuraminic acid:glycoprotein sialyltransferase(s) E.C. 2.4.99.1] was assayed using asialofetuin as a substrate in a total microsomal fraction obtained from rat liver. Rats pretreated with phenobarbital or methylcholanthrene demonstrated a decrease in membrane bound sialyltransferase(s) activity of 27% and 18%,respectively. Microsomes prepared from phenobarbital treated rats were incubated in vitro with aflatoxins B1, B2, B2a, G1, or G2 in the presence or absence of an NADPH generating system. Following this treatment the microsomes were reisolated, washed and assayed for sialyltransferase(s) activity. Aflatoxin B1 and B2a inhibited sialyltransferase(s) by 46% and 55%, respectively, while aflatoxin G1 inhibited sialyltransferase(s) by 54%. Aflatoxins B2 and G2 were only slightly inhibitory. It is proposed that the enzyme inhibition caused by these various aflatoxins is due to binding of these agents to the membranes resulting in a local disruption of the membrane and a change in enzyme conformation.


Reaginic antibody in cattle hypersensitised by foot-and-mouth disease vaccine. The passive cutaneous anaphylaxis test (PCAT) in calves and goats was used to demonstrate reaginic antibody in the sera of cattle which had shown anaphylaxis following injection with foot-and-mouth disease vaccine. A period of two or three days between the intracutaneous injection of test sera and the intracutaneous or intravenous challenge with components of vaccine was found to be satisfactory. Positive reactions were obtained in calves for up to 49 days but many goats failed to react after eight days. The PCAT had a high degree of reproducibility within any one test animal, but a marked variation was found between individual test animals.


Induction of hypersensitivity to carboxymethylcellulose in cattle. Cattle were more readily sensitised than guinea pigs to carboxymethylcellulose. Freund's complete adjuvant enhanced, but was not essential for, sensitisation. Schultz-Dale responses were obtained from pulmonary tissues of sensitised cattle but their sera failed to induce passive cutaneous anaphylaxis. Cattle could possibly be sensitised by carboxymethylcellulose contained in drug formulations.


[Cause and treatment of hydrocephalus in newborns and infants]. The history and classification of the various types of hydrocephalus are outlined and the mechanisms as well as causes of infantile hydorcephalus are discussed. Acoording to aetiology the possible operative treatments are described and special mention is made of ventriculocardiac shunting with its indications, advantages and complications. Finally, the results that may be expected from operative treatment of infantile hydrocephalus are studied and the neuropsychological aspect is emphasized.


Reiter's disease and the histocompatibility antigen, HL-A 27. HL-A27 were found in 31 of 48 patients with Reiter's disease (65%) as compared with 8% of 2 103 health controls. It is suggested that HL-A27 is closely related to the inheritance of a special immune response leading to an increased susceptibility to a special type of reactive arthritis which Reiter's disease has in common with ankylosing spondylitis and a certain type of psoriatic arthritis.


Symphysial changes in rheumatoid arthritis. A microradiographical and histological study. Autopsied pubic symphyses of 10 male and 10 female non-rheumatoid subjects and of 11 subjects with RA were studied. Osteo-arthritic changes were common in all elderly symphyses. This caused changes in the structure of the end plates and trabeculae. Some non-rheumatoid samples showed changes suggestive of erosion, but no evidence of inflammation. At microradiography the erosions seen in rheumatoid symphyses differed from the controls due to a lack of reactive sclerosis in the surrounding bone, although true inflammation was seen histologically in only two cases.


[Treatment of rhythm disorders following acute heart infarction using a beta receptor blockader (Visken)]. In a group of 40 patients with acute myocardial infarction and ectopic ventricular or atrial beats or tachycardia, the effect of Visken has been tested by means of 3 i.v. injections of 0.4 mg each at intervals of 15 min. The results showed that Visken has a good effect on these rhythm disturbances and can be administered without danger, provided due regard is had to the contraindications. Beta-blockade is especially indicated when the sinus rate is raised and the conventional antiarrhythmic drugs have proved ineffective.


Central projection of optic tract from translocated eyes in the leopard frog (Rana pipiens). In Rana pipiens embryos, eye anlagen were moved to the evacuated ear position, where they continued to differentiate and sent their optic nerve fibers into the hindbrain. Upon entering the medulla, the optic fibers turned caudally, penetrated the spinal cord, and traversed the dorsolateral white matter to the caudal end. We found this pattern of growth in every animal; the optic fibers did not enter the tecta. These results suggest the existence within the neural tube of a three-dimensional gradient system to which embryonic optic fibers are responsive and which may guide the normal development of the visual pathway.


Clinical aspects of invasive carcinoid tumors. In a retrospective study at the University of Louisville Affiliated Hospitals, 42 patients with carcinoid tumors not arising  in the anorectal area were identified in ten years (1962-1972). The ileum was the organ most frequently involved with primary tumor (28%). The nonappendiceal gastrointestinal tumors were multiple in 28%, metastatic in 66%, and associated with a second malignancy in 25%. Of the symptomatic small-bowel tumors, 83% were metastatic at the time of diagnosis. Carcinoid syndrome was observed in only two patients, both of whom had liver metastases and elevated urinary 5-HIAA levels. Resections for cure were done on 25 patients, palliative resections on six, and biopsy on six. Six tumors were from autopsy meterial. Among the 24 patients treated and followed up for five years, the survival rate was only 16%. In those patients having resection for cure, the five-year survival rate was 39%, exculding appendiceal tumors. The advanced stage of disease at time of discovery and the dismal prognosis for invasive carcinoids are contrary to many clinicians' impressions of the nature of carcinoid tumors but entirely consistent with several other recent reports (James Ewing Society meeting, April 1973).


Peritoneal mesothelioma presenting as an adnexal mass. A case of primary peritoneal mesothelioma which presented clinically as an adnexal mass is reviewed. Difficulties in diagnosis and factors affecting prognosis are discussed. Operation to remove as much of the tumor as possible, followed by irradiation therapy, is suggested as a worthwhile approach to improving chances for cure or palliation.


Acute biochemical and histological effects of portacaval shunt in the normal rat. In previous studies of rats with portacaval shunts, elevated gamma-globulin levels 2 weeks after shunt were attributed to antibodies to bacterial lipopolysaccharide, which were normally filtered by the liver. This study was designed to determine the tempo of this rise and the magnitude of hepatocellular damage within the first 4 days of the operation. Acute reversible hepatocellular damage was shown by elevated levels of aspartate aminotransferase which returned to normal within 48 hours. This was confirmed on histology. There was no rise in gamma-globulin during this study but levels of albumin were better maintained in shunted rats than in sham-operated rats. Levels of alpha2 and beta-globulin in the former fell in comparison with the latter animals.


Solitary myeloma. A study of 10 black patients during an 8-year period. Solitary myeloma of bone occurred in 10 Black patients during the 8-year period from 1967 to 1974. In 4 patients, the solitary myeloma involved the bones of the paranasal sinuses, in 3 patients the pelvis, and in 3 others the manubrium sterni. An IgG monoclonal gammopathy was present in the serum of 4 patients and Bence-Joanes proteinuria was found in 1 patient. Radiation therapy was the treatment of choice and the recommended tumour dosage is 4000-5000 rads. Serial measurements of serum and urine protein electrophoresis and immuno-electrophoresis were most helpful in determining when patients had achieved a complete remission. In 3 patients, 1 of whom died, the myeloma disseminated in periods varying from 26 months to 7 years. Nine patients are alive, of whom 7 are in complete remission, and 5 have lived for more than 5 years since the initial diagnosis of solitary myeloma.


Effects of antineoplastic agents on wound healing in mice. The influence of antineoplastic agents on wound healing was evaluated in an experimental model employing surgical incisions in the skin of mice. A single injection in the therapeutic dose range of various clinically active antitumor agents was administered immediately following operation and the breaking strength of skin wounds was measured 3, 7, and 21 days later. Vincristine and methotrexate decreased wound strength at 3 days but not on days 7 or 21. Actinomycin D interfered with early phases of wound healing and had less effect on later phases. Treatment with bleomycin had no effect on wound strength at days 3 or 21 but prevented an increase in wound strength from day 3 to day 7; 1,3-bis(2-choroethyl)-1-nitrosurea (BCNU) decreased wound strength at all time points after operation, whereas 5-Fluorouracil had no significant effect at any time. The presence of a large tumor mass had no direct effect on wound strength nor did it modify the effect on wound strength of an antineoplastic agent, cyclophosphamide. These findings are discussed, taking into account the experimental and clinical literature on the effects of antitumor drugs on wound healing.


A study on HL-A system in Japanese.

A study on HL-A system in Japanese. Two hundred unrelated Japanese individuals were HL-A typed with UCLA Research Tray T3 (Terasaki's Tray), which contains specificities added after the Fifth International Workshop. Phenotype, gene and haplotype frequencies were calculated with standard errors and delta values. HL-A9, HL-A5 and W10 had a higher frequency and HL-A1, 3 and 8 had a lower frequency in Japanese than in Caucasians. The frequent haplotypes were HL-A9-HL-A5, HL-A9-HL-A7 and HL-A2W10. HL-A9-HL-A5 showed very positive high linkage disequilibrium parameter (delta value) and HL-A9-W10 showed negative high value. The sera designated as anti-HL-A, W5 and W15 in the T3 Tray which react identically in Caucasians showed different patterns of reaction when tested in the Japanese population. Five hundred Japanese parous women's sera were tested for cytotoxic antibodies. Some Japanese antisera showed high correlation coefficient values on HL-A2, HL-A9, HL-A10, HL-A11 and HL-A12. The women providing the anti-HL-5 complex sera and their immunizing persons were HL-A typed. These complex sera reactions were compared with the antisera in the T3 Tray. A new group of sera (SN-1), "operationally monospecific" and cross-reacting with W22, was found in the present study. Population and family studies suggested that the sera SN-1 are third in frequency within the second series (phenotypic frequency 17-22%) and show high delta values with HL-A11 in the Japanese population.


HL-A antigen frequencies in myeloma.

HL-A antigen frequencies in myeloma. The frequency of HL-A antigens was determined in 63 myeloma patients and in 83 normal subjects. HL-A5 was more frequent among patients (15.9%) than among controls (3.6%). This association was significant at the 0.05 level, but the significance did not survive multiplication by the number of antigens under study. The relationship of these findings to previous work on myeloma is discussed, together with the problems of defining components of the 4c antigenic group.


Third HL-A segregant series: genetic analysis and molecular independence on lymphocyte surface. Five sera which detect two alleles of the third HL-A locus (T2 and T4) are described. Statistical analysis of a panel of 220 donors gave gene frequencies in a French Parisian population which are comparable to the results of  Scandinavian authors. Segregation observed in 50 families emphasized the linkage disequilibrium with SD2 alleles. T1 was found to be associated with one part of W22 (Da30) and T3 with the other part non-Da30). No recombination was observed between SD2 and SD3, and the distance between these two loci can be estimated at less than 0.0042 U. Differential capping experiments showed that redistribution of SD3 antigens did not affect the SD2 or SD1 products, indicating that they are borne on the cell surface by independent structures. Moreover, capping of SD1, SD2 and SD3 antigens did not provoke complete redistribution of beta2microglobulin which suggests that not all beta2M molecules are linked to HL-A antigens.


Direct cell mediated lympholysis. A test of allograft-rejection in human kidney recipients. In kidney transplanted patients a clear coincidence was observed between clinical signs of allograft rejection and the presence in the peripheral blood of killer cells able to lyse either PHA lymphoblasts from the actual donor or selected unrelated individuals. In recipients with non-immunological complications such as leakage on the graft ureter or primary anuria caused by renal ischaemia, no cellular cytotoxicity against specific or selected target cells was observed. The specificity of this Cell Mediated Lympholysis in two of the cases reported could not be explained by the serologically detectable HL-A antigens, indicating the existence of other determinants of importance for the killing capability of in vivo produced effector cells.


Low HL-A2 frequency and periodontitis.

Low HL-A2 frequency and periodontitis. The frequency of HL-A2 was significantly low (21%) in patients with periodontitis when compared to controls who were free of periodontal disease (61%). The effect was most pronounced in females in whom HL-A2 was present in 12.5% (2 out of 16). This finding suggests that genes controlling susceptibility to microbial agents may be linked to the HL-A LOCUS.


An analysis of the 4c complex of HL-A based on Indian populations. Sera detecting part or all of the 4c group of HL-A antigenic specificities were compared in two American Indian populations, the Ixils and the Pimas, and in one Spanish-Indian hybrid population, the Mestizos of Peru. Several new variants appeared. These were not identical to HL-A5, W5 or W18. Two of the variants appeared to represent specificities Z57 and Z51 as described during the 1972 Histocompatibility Testing Workshop. In addition, three new specificities could be detected. These were Z42, Ao88 and Ao93. Z42, Ao88 appeared to belong to the 4c complex and Ao93, a new specificity of the second locus, may belong to this same cross-reactive group.


An inclusion analysis for studying HL-A specificities. INCLAN (Inclusion analysis) is a computer program which provides a systematic search for the subtypic variants of a given serological specificity. This routine was found especially useful for the HL-A serology whose complexity often needs automatic displays. A detailed description of its structure is presented in this note.


Typing for MLC determinants using lymphocytes from cousin-marriage offspring as typing cells. A first cousin marriage family with three children was studied. One sibling (AW) was homozygous for W32.W10. When used as stimulator in one way MLC, AW elicited a very low response in family members possessing this haplotype. Serologically identical sibling and father combination showed bidirectional non-stimulation in one way MLC. Therefore, AW is assumed to be homozygous not only for SD antigens, but also for LD determinants which we call LD W10a. Among the 43 unrelated individuals tested with AW, an association between LD W10a and W10 antigen of the second HL-A locus was observed. Of 12 W10 positive individuals tested, five carry this allele as compared to one out of 31 W10 negative individuals. The data suggest a strong linkage disequilibrium between the FOUR locus determinant W10 and LD  determinant LD W10a.


HL-A antigens in a Chinese population.

HL-A antigens in a Chinese population. The HL-A antigens of a Chinese population now living on the island of Taiwan have been investigated with reagents obtained from and characterized in Caucasian populations and with antisera obtained from Chinese multiparous women. Both HL-A2, the most frequent specificity found, and HL-A9 appear highly heterogeneous in this Chinese population since groups of antisera used to define HL-A2 or 9 in Caucasians gave discordant reactions. Moreover, new associations were found using chi-square and cluster analyses, further demonstrating the complexity of HL-A in this Taiwanese population. Fourteen % of 1183 Chinese multipara sera and 237 sera from multiple tranfused individuals were lymphocytotoxic and could be placed by cluster analysis into three major groups.


LD typing in man using cells frozen and stored in microtiter plates. A method of freezing LD typing cells in microtiter plates was developed. Two times 10(5) lymphocytes in a small volume (15 mul) with a low DMSO concentration (5%) were directly frozen in a --70 degrees C freezer. These cells were used in the mixed lymphocyte culture after thawing by diluting step-by-step with serum and culture medium without washing. The kinetics obtained with cells frozen in microtiter plates were comparable to those with fresh cells. Typing for LD determinants was performed in a group of unrelated persons in a family study using the LD homozygous reference cell Pi frozen in microtiter plates.


Plasma diethylstilboestrol binding proteins of rat, mouse and man in the course of development: relations with the binding of estradiol. High diethylstilboestrol (DES) binding has been demonstrated in fetal and adult sera from man, rat and mouse by equilibrium dialysis and electrophoretic techniques. In the adults of the three species and in the human fetus only albumin shows an elevated binding capacity for DES. By contrast, in the case of rat and mouse embryos there are two proteins, namely albumin and alpha-fetoprotein, which afford major and quantatively similar contributions to the binding. Human alpha-fetoprotein does not bind DES. These phenomena are analysed in relation to the estrogen binding characteristics of the alpha-fetoproteins of the three species.


Association of beta-2-microglobulin and HL-A in the cell membrane. A general property in human cells? To study whether the recently reported close association of beta-2-microglobulin and HL-A determinants is restricted to lymphocyte membranes or might be a more general property, experiments were performed where normal and malignant human cells were tested for coaggregation-capping of the two determinants. The normal cells were fibroblasts and the epithelial cells were from skin. The turmor cell lines were HeLa clone S3 carcinoma cells and National Collection of Type Cultures strain 3075, which is a line of malignant human skin cells. The cells were double-stained with fluorescein-labelled conjugates to demonstrate the reaction of anti-HL-A and anti-beta-2-microglobulin with the respective cell membrane components. Aggregation and capping of the HL-A and beta-2-microglobulin determinants in the cell membrane were always observed after incubation at 37 C for 30 min. The red and green fluorescence were always superimposed when anti-beta-2-microglobulin was used in the first (aggregating) incubation step. This demonstrates that the HL-A and beta-2-microglobulin determinants are also associated in the cell membrane of cells other than lymphocytes.