Neurotransmitters and the fifth cranial nerve: is there a relation to the headache phase of migraine? The headache phase of migraine may develop as the result of an abnormal interaction (and perhaps an abnormal release) of vasoactive neurotransmitters from terminals of the trigeminal nerve with large intracranial and extracranial blood-vessels. These blood-vessels, which dilate during the headache phase of migraine, are thought to receive axonal projections from all three divisions of the trigeminal nerve. Substance P, a potent vasodilating peptide, seems to be released from trigeminal nerve endings in response to nervous stimulation and is involved in the transmission of painful stimuli within the periphery. The vasoactive molecule serotonin, implicated in the pathogenesis of migraine, coexists with substance P in some terminals of the central nervous system and is present within the trigeminal ganglia. Within this nerve serotonin may modulate the function of primary sensory neurons. The abnormal release of substance P or as yet unidentified peptides or other transmitters from the fifth cranial nerve may explain both the hemicranial pain and the vasodilation which are characteristic of the headache of migraine.


Fish-eye disease. A new familial condition with massive corneal opacities and dyslipoproteinaemia. A man and his three daughters had massive corneal opacities called in their home village "fish-eye disease" because of the resemblance of the eyes to those of boiled fish. The two living daughters had the same dyslipoproteinaemia, characterised by normal serum cholesterol but raised serum triglycerides, raised very-low-density lipoproteins, strikingly high levels of low-density lipoprotein (LDL) triglycerides. LDL contained normal sized as well as abnormally large particles and a 90% reduction in the level of high-density lipoprotein (HDL) cholesterol. Lecithin:cholesterol acyltransferase (LCAT) activity and the percentage of plasma cholesterol esters were normal, with excluded LCAT-deficiency. Normal electrophoretic mobility of HDL as well as other lipoprotein findings excluded Tangier disease. The clinical and laboratory abnormalities in fish-eye disease are atherosclerosis at old age, visual impairment, and dense corneal opacification. Fish-eye disease thus differs both clinically and in its lipoprotein abnormalities from LCAT-deficiency and Tangier disease.


Combined use of guar and acarbose in reduction of postprandial glycaemia. Symptoms associated with carbohydrate malabsorption limit the usefulness to diabetics of a powerful glycoside-hydrolase inhibitor (acarbose) which reduces postprandial glycaemia. Addition of a low dose (50 mg) of a acarbose together with 14.5 g guar gum to a breakfast test meal taken by 8 healthy volunteers reduced the mean peak rise in blood-glucose at 30 min by 70%. Areas under the insulin and gastrointestinal-polypeptide response curves were also greatly reduced. No evidence of carbohydrate malabsorption, as assessed by measurement of breath hydrogen, was found during any of the test periods. When acarbose was taken alone, 3 of the 8 subjects had troublesome symptoms and the 30 min rise in blood-glucose was reduced by only 28%. Thus, combination of these two agents effectively reduces the rate of carbohydrate absorption without increasing side-effects and may make combined acarbose and guar acceptable in the management of some diabetics.


Atypical Legionella-like organisms: fastidious water-associated bacteria pathogenic for man. A group of related bacteria designated atypical Legionella-like organisms (ALLO) has been identified. ALLO, like L. pneumophila, are fastidious gram-negative rods that grow well on charcoal yeast extract (CYE) agar and produce ground glass colonies and browning of modified yeast extract agar. Unlike L. pneumophila, ALLO do not grow well on Feeley-Gorman (FG) agar, and on CYE agar they fluoresce under longwave ultraviolet light. ALLO and L. pneumophila have a similar predominance of branched-chain forms among total cellular fatty acids but have distinctive fatty-acid profiles. 2 patients with culture-verified ALLO pneumonia and 10 with pneumonia of uncertain aetiology who seroconverted to ALLO offer evidence that ALLO may be a cause of community-acquired pneumonia. Like L. pneumophila, ALLO appear to be water-associated; both persons with culture-verified ALLO infection were exposed to fresh water or its contents before becoming ill, and two strains of ALLO were isolated from water or wet environments.


Modulation of plasma 1,25-dihydroxyvitamin D in man by stimulation and suppression tests. In normal volunteers infusion of parathyroid extract raised plasma 1,25-dihydroxyvitamin D (1,25-[OH]2D) levels by 80% (peak 8--40 h after infusion) without producing any significant change in plasma calcium, phosphate, or magnesium. An oral calcium load suppressed plasma 1,25-(OH)2D to 63% of control values within 48--72 h. These responses will be useful in the diagnosis and management of disturbances of calcium and mineral metabolism in which vitamin D metabolism is abnormal.


Effect of oral contraceptives on platelet noradrenaline and5-hydroxytryptamine receptors and aggregation. Characteristics of receptor sites on platelets for noradrenaline (NA) and serotonin (5-HT) changed significantly between day 21 and day 28 of treatment in healthy women taking oral contraceptives. NA-induced and 5-HT-induced platelet aggregation and 5-HT uptake vaired accordingly. In untreated women with normal cycles no changes in either receptor site or in platelet function occurred between the luteal and postmenstrual phases. It is concluded that the observed changes are due to a pharmacological effect of the oral contraceptive rather than a normal physiological variation.


Cure of Burkitt's lymphoma. Ten-year follow-up of 157 Ugandan patients. 192 Ugandan patients with Burkitt's lymphoma were treated with various regimens containing high-dose cyclophosphamide. 21 patients died during induction therapy, and 14 died after partial responses. Of 157 patients who responded completely to treatment, 16 were lost to follow-up (10 in 69 died and 72 (51%) are alive and disease-free. 31 of the long-term survivors have relapsed at least once and have been successfully retreated. Overall, 34 surviving patients had central-nervous-system involvement, also successfully treated. It is concluded that Burkitt's lymphoma is curable in at least 50% of patients, and that relapse and central-nervous-system involvement are not incompatible with long survival.


Is the fetus "scalped" in labour?

Is the fetus "scalped" in labour? Capillary blood-flow and tissue oxygenation of the scalp and/or forearm skin were measured in the three adult volunteers. Skin pressure required to occlude circulation was much lower for the scalp than for the forearm skin, and tissue oxygenation fell rapidly when capillary blood-flow fell below about 3 ml/100 g tissue/min. Since scalp circulation is not representative of the general circulation when pressure is applied, the tissue oxygenation level of the fetal scalp in labour (obtained by direct sampling or by transcutaneous electrodes) is not a good indicator of the well-being of a fetus.


[Surgery in patients with obstructive jaundice caused by carcinoma (author's transl)]. Malignant disease obstructing the bile ducts is diagnosed in most cases at a time, when radical surgery is not possibly any more. Diagnostic procedures applied up to now are not suited for early diagnosis. 5 years survival rates of patients with carcinoma of the bile ducts are maximally 6%, in patients with carcinoma of the papilla 36%. In the Department of Surgery of the Münster University, 126 such patients have been treated in the recent time; in 104 cases jaundice was apparent clinically. Radical pancreatoduodenectomy could be done only in 24 patients.


[The color rendition of microscopical stains by the dyes produced in reversal color films (author's transl)]. When comparing spectral and colorimetric data of colors of our natural environment with the data of microscopical stains, we observe considerable differences in spectral transmittance respectively reflectance. Furthermore, the spectral locus of these colors are situated at very different positions in the color space or in a chromaticity diagram. By this reason, we must anticipate that usual color reversal materials being optimized in the very first line for the reproduction of colors like foliage green, sky blue or earth, cannot render the hues of histological stains in a satisfying manner. To prove this assertion, the reproducible ranges of hues in the color space were calculated by means of the spectral densities of the dyes developed in the three layers of various color reversal films, and these results were then compared with the spectral data of some stains often applied for histology (H-E, Goldner, Azan etc.). By this method, we find that no color film examined can reproduce in a sufficient manner all these stains at the same time. The results can allow for color micrography the selection of a definite film for best possible color matching of a least one interesting range of color.


[Present state of resistance to antibiotics by tuberculous bacilli in Africa (author's transl)]. Tuberculous bacilli isolated from recently infected patients from various african countries, are resistant to the main specific antibiotics. The present study analyses these resistances which are frequent and mainly directed against INH and streptomycin. Resistance against INH is frequently associated, and is due to inadequate monitoring of the treatment. The resistance against streptomycin is probably due in part to the frequent use of streptomycin against common non-tuberculous infections. The high frequency of thiacetazone resistance is associated with the geographical distribution of M. africanum. Given the situation, it is necessary to consider discarding this drug and replacing it. Unfortunately however, the most recent antibiotics, which have not yet generated resistant strains, are often too expensive.


[Mycobacterium africanum (author's transl)]. A restatement about M. africanum. Diagnosis is based on the aspects of cultures and some biochemical features. Its resistance potentiality is that of M. tuberculosis except for Tb 1 with which resistance is very frequent. It has a rather low experimental virulence and seems to be confined to Africa.


Feulgen type staining with Hoffmann's violet-SO2 under exposure to UV rays. The paper contains an account of the use of Hoffmann's violet-SO2 under exposure to UV rays during staining acid-hydrolysed DNA of mammalian tissue nuclei. Preparations stained with Hoffmann's violet-SO2 without exposure to UV rays reveal extremely pale violet nuclei but when stained under the influence of UV rays show a considerably faster reaction resulting in a very much deeper staining of the nuclei. Sections after staining with this dye-reagent require n-butanol as differentiating reagent. Possible interpretation for the increase in staining ability of this dye-reagent under exposure to UV rays has been elucidated and the reason for considering the reaction as Feulgen type has been discussed.


Hydrochloric acid-sodium thiosulphate-Schiff reagent and its cytochemical properties. Cytochemical properties of modified Schiff reagent, prepared with 5 ml of N HCl and 1.0 g of sodium thiosulphate, the latter replacing potassium metabisulphite, have been presented in this communication. It has been seen that such a modified Schiff reagent has a slightly elevated pH as compared with that of the conventional Schiff reagent. It has also been found that this modified Schiff reagent has a much longer shelf-life and that the staining intensity produced by this dye-reagent is more than those of the usual Schiff reagent prepared with N HCl and potassium metabisulphite (potassium pyrosulphite, K2S2O5). Possible mechanism as to why the staining intensity of the nuclei is more with this modified Schiff reagent as well as the reason as to why its shelf-life is increased compared with those of the conventional Schiff reagent have been discussed.


Soluble immune complex disease associated with antigen heterogeneity an HLA related disorder. It is suggested that soluble immune complex diseases arising after infections may result from the liberation of partially synthesized bacterial polypeptide or viral nucleic acid antigens. These disrupted antigens will have heterogeneous molecular weights due to antigenic material which is incomplete as a result of premature termination of synthesis. Antigens of this type have been shown to result in significant soluble complex formation in vitro when reacted with antisera from many individuals. Interestingly, this was demonstrated using an antigen which has been instrumental in defining, in the mouse, immune response genes. These genes are known to be linked to genes which code for lymphocyte antigens. If particular immune response genes are linked to HLA types in humans, as is thought to be the case, there may be a large number of soluble immune complex diseases caused by infectious agents which may be HLA type associated.


The hepatitis B virus and its DNA polymerase: the prototype three-D virus. The hepatitis B virus (HBV), the causal agent of serum hepatitis, has a diameter of 42 nm and is comprised of an outer surface coat and a 27 nm core. A unique DNA-dependent DNA polymerase is associated with the core of the virus. The core also houses a circular DNA that contains both double-stranded and single-stranded regions. In the endogenous reaction, the DNA polymerase repairs the single-stranded gaps of the viral DNA. The surface protein of the virus, called hepatitis B surface antigen, contains both lipid and carbohydrate, and is often present in particulate form in the blood of infected patients. In Asia and Africa HBV infection is associated with subsequent development of primary hepatocellular carcinoma. Although most patients recover completely from acute illness, the hepatitis B virus may cause chronic infection. Recently, a virus similar to human HBV was discovered in woodchucks. HBV has not yet been propagated in a cell culture system and the mode of replication of this unusual virus in hepatocytes is still moot. Although reliable therapy has not yet been provided, the problem of this world-wide infection has led to many interesting approaches to both vaccine production and anti-viral chemotherapy.


[Psychosocial consequences of head injuries in children (author's transl)]. Psychosocial consequences of head injuries in children can be understood in terms of an interaction between pretraumatic conditions, conditions and sequelae of the trauma (injury) and posttraumatic factors. The results of these interactions in the area of psychosocial functioning can be defined as effects on development in general as well as effects on school behaviour, occupational and family situation. Taking into account these factors, and the reaction of the famility, two major reactions can be identified: (1) Insisting on the until now practised attitude to the child, (2) Abrupt changing of the attitude to the child after head injury. Both reactions lead to an inadequate handling of the child and in consequence to overtax or overprotection. Finally, also the reaction of the child has to be taken into account. It should be integrated into the rehabilitation program. There seem to be differences between children with slight and severe head injuries.


[Disturbances of mental development in infants and preschool children. Their recognition and treatment (author's transl)]. After a short introduction setting out the importance of development dimensions for the understanding of disturbances of development and some statistics on the frequency of peculiarities of behavior in the preschool age, some disorders of mental development of practical importance in the first years of life are dealt with. Psychomotor disturbances, disorders of speech and speaking and emotional and contact disturbances are emphasized.


[Radicular and pseudoradicular symptoms of the middle and lower cervical vertebral column (author's transl)]. The differential diagnostic classification of the "shoulder-hand-syndrome" according to etiology and pathophysiological principles is of major importance. The radicular syndrome, subsumed as the shoulder-hand syndrome following a local lesion, must be exactly defined. The pseudoradicular syndrome, which frequently appears clinically in the cervical region under the guise of middle and lower cervical syndrome, has its cause in disturbed function of the vertebral joints. But it can also arise as a mixed syndrome, radicular and pseudoradicular, through a substantial root lesion. The diagnosis of a referred pain in a "shoulder-hand syndrome" can lead to the discovery of internal organic lesions or lesions of the locomotor apparatus of the extremities.


[Diagnosis and clinical aspects of the cervicobrachial syndrome as seen by the rheumatologist (author's transl)]. Among the various diseases classified as cervicobrachial syndrome, from the rheumatological point of view rheumatic conditions of the soft parts such as periarthritis humeroscapularis, tendomyoses and insertion tendinoses are particularly important. Their exact clarification and differentiation from polymyalgia rheumatica and the rare polymyositis is also of great therapeutic significance. Moreover the rheumatologist is also frequently confronted with inflammatory and non-inflammatory conditions of the cervical vertebral column and the shoulder joint which may set up various disease symptoms. A whole series of affections come into consideration in the differential diagnosis and they are summarized in a table.


[The psychosomatics of pain, particularly in the cervicobrachial region (author's transl)]. A description is first given of the relevance of emotional factors to present-day pathological processes. Pain may be indicative of various causes: consecutive symptom of an organic process, expression of a functional disorder, emotionally conditioned symptom. The vicious circle of pain and emotion (anxiety, aggression, depression) is demonstrated as exemplified by nonarticular rheumatism. Tension revolt and suppressed aggression play a fundamental role in the cervicobrachial syndrome.


Effects of caffeine on chromosome aberrations and sister-chromatid exchanges induced by mitomycin C in BrdU-labeled human chromosomes. The BrdU-Hoechst staining technique has been used in analyzing the effect of caffeine (CAF) on chromosome aberrations and sister-chromatid exchanges (SCEs) induced by mitomycin C (MC). CAF increased the frequency of SCE in MC-treated chromosomes in all specimens. The combination of MC and CAF caused a remarkable increase in all types of chromosome aberrations, but the most startling effect was the appearance of many cells with multiple aberrations (shattered chromosomes). The BrdU-Hoechst technique showed that the shattered chromosomes did not appear in cells that had replicated only once, but did occur in cells which replicated twice in the presence of MC and CAF. The large majority of chromatid breaks observed did not involve areas common to SCE; and the SCE frequency significantly increased in spite of the existence of multiple breaks. This indicates that very few of the breaks are incomplete exchanges and that the mechanism for formation of SCE might be different from that of chromosome breaks. In another experiment, monofunctional-MC (M-MC) had a small effect on SCE rates, though it induced shattered chromosomes with CAF post-treatment. Possible differences in the mechanisms leading to SCE and chromosome breaks are discussed.


Blastomycosis: report of three cases from Alberta with a review of Canadian cases. Approximately 120 cases of blastomycosis have been reported from Canada to-date. The great majority of these occurred in the Eastern provinces. Since 1970, three cases of blastomycosis have been seen in Alberta. The first case, with meningeal and pulmonary involvements, was diagnosed at post-mortem. The second case was that of a 75-year-old male with a history of pancytopenia, aortic arteriosclerosis, exposure to mercury, and fever. KOH and periodic-acid schiff (PAS) stained smears of the lung tissue, received after autopsy, showed numerous budding yeast cells of Blastomyces dermatitidis along with some hyphal filaments. Similarly, budding cells of B. dermatitidis and hyphal segments were observed in large numbers in the PAS and Gomori's methenamine-silver (GMS) stained sections made from adrenals, lung, kidney, and spleen tissues. Attempts to culture the fungus on a variety of selective and non-selective media were unsuccessful, due to heavy bacterial contamination. The indirect fluoroscent antibody results were 2+ with the B. dermatitidis conjugate. The third case was that of a 31-year-old male, who was admitted to the hospital with the chief complaint of chest pain. Biopsy tissue sections, stained with the GMS procedure revealed a few foci with B. dermatitidis yeast cells. The immunodiffusion and complement fixation (CF) tests gave positive results against B. dermatitidis antigen (titre, 1:16). The CF titre declined following treatment with amphotericin B and the immunodiffusion test became negative after the institution of antifungal therapy. Except for the last patient, the other two patients had no history of travel in any known endemic areas. In addition to these cases, a survey of blastomycosis occurring in this country has been presented along with on the disease in dogs and a cat.


Axonal transport of vasoactive intestinal peptide in sciatic nerve. Dense plexuses of neurones containing immunoreactive vasoactive intestinal peptide (VIP) have been found in discrete areas of the central nervous system and in peripheral organs, including the gastrointestinal tract, pancreas and urogenital system. In many of these locations VIP is concentrated in nerve endings, where it can be released by high K+ concentrations in a Ca2+-dependent manner. VIP release may also be provoked by electrical stimulation of nerves, for example the vagus. VIP thus shows some of the features of neurotransmitter or neuromodulator substances. The presence of immunoreactive VIP in the fine terminal varicosities as well as in the cell bodies of neurones suggests that it might be transported from the perikaryon, where it is presumably formed, to the nerve endings, through the axonal transport system. Such transport would be in keeping with a role for the peptide as a neurohumor or neurohormone. We report here that VIP accumulates in constricted rat sciatic nerves in a manner suggesting fast, anterograde axonal flow.


Lysozyme-induced T-suppressor cells and antibodies have a predominant idiotype. The existence of shared idiotypic determinants on the surfaces of T and B cells is now firmly established, suggesting that on both these cell types immunoglobulin variable regions are expressed which presumably function as antigen receptors. In most systems this has been inferred through the use of anti-idiotypic antibody instead of antigen to induce either helper or suppressor T cells. Recent evidence demonstrates that antigen-specific suppressor or helper factors can also bear idiotypic determinants. It is possible that these factors represent released receptors or portions of receptors. We show here the direct elimination of an antigen-induced T-suppressor  population by an anti-idiotypic serum and complement. These suppressor T cells as well as the idiotypic population used to generate the antiserum are each specific for the same limited portion of the multi-determinant antigen, lysozyme. Apparently, these suppressor cells are restricted in specificity as well as share idiotypy with antibodies of the same specificity.


Prenatal diagnosis using amniocentesis: the Christchurch experience. A service for biochemical analysis of amniotic fluid has been available since 1975. A total of 186 early pregnancy samples were received, the majority were from patients at risk for chromosome abnormalities or neural tube defects. The indications for analysis and the problems related to the results are presented and the need for an established genetic counselling system with a supra-regional assay service is discussed.


[Effect of the nude mutation on alpha-fetoprotein synthesis and hemopoiesis in the mouse liver in the postnatal period of development]. The dynamics of population of alpha-fetoprotein (AFP)-containing cells in the liver and the level of AFP in the blood of C3H/HeJ+/+ and thymus-less mutant C3H/HeJnu/nu mice during postnatal development was studied by means of indirect immunofluorescence and radial immunodiffusion. The content of AFP-positive hepatocytes and AFP concentration in the blood serum of C3H/HeJnu/nu mice were shown to exceed markedly those in C3H/HeJ+/+ mice beginning from the age of 2 weeks. The histological analyses has revealed the foci of hemopoiesis in the liver of adult C3H/HeJnu/nu mice, unlike in the liver of normal mice. The neonatal thymectomy of C3H/HeJ+/+ mice did not influence the parameters under study. A possible relationship between the increased AFP level and the preservation of hemopoiesis in the liver of the mice homozygous by the mutation nude is discussed.


Fluorescence iris angiography in the assessment of calcium dobesilate therapy in the treatment of diabetic microangiopathy. The authors employed fluorescence iridography and to evaluate the changes induced by a 1-year treatment with calcium dobesilate.


Oxytalan fibers in peripheral odontogenic fibromas. A histochemical study of eighteen cases. Oxytalan fibers, identified by histochemical methods alone, were found embedded. Since oxytalan fibers have been found embedded in bone in the periodontal ligament, the finding of these fibers in the calcified material of peripheral odontogenic fibromas adds considerable weight to the assumption that these lesions are of periodontal ligament origin.


Primary care approaches to developmental disabilities. Ninety-seven board certified pediatricians who spend at least 75% of their professional working hours involved in the delivery of primary care in New England were interviewed to explore their attitudes and current clinical approaches to developmental disabilities. The majority of the pediatricians relied exclusively on clinical judgment and general observations for assessing developmental problems in their offices. Responsibility for preschool screening for potential learning problems and the assessment of school failure were considered appropriate pediatric concerns. Reported customary approaches to a variety of developmental problems were not affected by the size of the practice nor by the socio-economic status of the patient population. Patterns of referral for consultation appeared to be more dependent on the nature of the suspected disorder than on the characteristics of the physicians or their practices. The need for more rigorous training in the developmental aspects of child health has been emphasized. In order to meet this challenge, more precise techniques for pediatric developmental assessment and more conclusive evaluations of specific interventions will have to be produced.


Applied teaching concepts of animated motion slides in otolaryngology. Motion is an essential part of otolaryngologic function, and an understanding of concepts of motion is critical in teaching otolaryngology. Standard movie projection devices have intrinsic defects, such as considerable expense to make, complexity of operation, and a lack of flexibility. Slide projection transparencies (2X2) offer instructional flexibility but could not be used to project motion until recently. Using applications of gelatin films of images with polarizing light, we have been able to produce an illusion of motion similar to that used in creating the motion in cartoons. We have produced a series of slides for instructional purposes to show concepts in otolaryngology.


Hybridization properties of sequences adjacent to triphosphorylated 5'-ends of nuclear pre-mRNA from mouse Ehrlich carcinoma. Triphosphorylated 5'-end fragments about 100 nucleotides long were prepared from purified nuclear pre-mRNA using a modified hydroxyapatite method /1/. These fragments as well as fragments of total pre-mRNA of the same size were polyadenylated in vitro by ATP:RNA adenyltransferase and used as templates for the synthesis of [32P] cDNA by reverse transcriptase in the presence of an oligo(dT) primer. The use of cDNA transcribed from the triphosphorylated 5'-end fragments of pre-mRNA (5'-cDNA) and from the total pre-mRNA fragments allows one to calculate the complexity of the 5'-end fraction pre-mRNA and to detect these sequences in polysomal mRNA. Sequences adjacent to 5'-phosphorylated ends of pre-mRNA represent a specific class of sequences with a complexity of about 200 kb. It was also found that about 25% of total pre-mRNA and about a half of sequences adjacent to triphosphorylated 5'-ends are present in polysomal mRNA. A high homology between triphosphorylated 5'-end fragments of pre-mRNA and mRNA sequences may be explained in terms of splicing. Less than 30% of 5'-cDNA hybridized to moderately repetitive DNA while most of them are represented by unique DNA sequences. About 15% of 5'-cDNA contained oligo(dA) sequences originated from oligo(U) in pre-mRNA from which it was transcribed.


Reverse transcriptase mediated binding of primer tRNA to the viral genome. A complex between tRNATrp (beef) and 35 S RNA from avian myeloblastosis virus is obtained when the mixture is preincubated in the presence of reverse transcriptase at 35 degrees C. The tRNA-RNA complex is active in initiating DNA synthesis catalyzed by reverse transcriptase. The interaction of tRNA with reverse transcriptase involves the partial unwinding of the acceptor stem of tRNA, as evidenced by nuclease digestion with RNAase T1 and micrococcal nuclease. When tRNA2Glu (coli), having a high degree of similarity with primer tRNA at the level of the acceptor stem, was used as primer for DNA synthesis, a low but significant level of incorporation was obtained, if the reaction was performed at 35 degrees C, while a high incorporation, similar to the one obtained with tRNATrp was obtained when the annealing between tRNA2Glu and 35 S RNA was performed at 80 degrees C. Our evidences point out to an important role of the viral DNA polymerase in positioning the primer on the RNA genome.


alpha 1-Fetoprotein mRNA of rat yolk sac and hepatoma. Rat alpha 1-fetoprotein mRNA was isolated and purified to apparent homogeneity by means of immunoadsorption and oligo (dT) cellulose affinity chromatography. Purified AFP mRNA migrated as a 21S peak in 2.5% SDS-polyacrylamide gels. The translation product of this mRNA in micrococcal nuclease treated reticulocyte lysate was identified as AFP by specific immunoprecipitation, SDS-gel electrophoresis and tryptic digestion analysis. DNA complimentary to AFP mRNA was synthesized with avian meyloblastosis virus RNA-dependent DNA polymerase. This AFP cDNA was used as a probe to quantitate AFP mRNA in the developing rat liver and to compare the complexity and diversity of AFP mRNA derived from the normal rat liver and Morris hepatoma 7777. We found that the amount of functional AFP mRNA is decreasing during liver development. There is very little, if any, AFP mRNA in the adult rat liver. A high degree of homology between the AFP mRNA sequences of yolk sac and hepatoma was also found.


Sequence homology adjacent to the 3' terminal poly(A) of cowpea mosaic virus RNAs. We have determined the sequence of 80 nucleotides adjacent to 3' poly(A) of both (middle and bottom component) cowpea mosaic virus RNAs, using dideoxynucleotide termination of reverse transcription. Sequence conservation is indicated, there being about 80% homology between the first 65 bases of each RNA. Although both RNAs are polyadenylated, there is no AAUAAA sequence as associated with most known polyadenylated mRNAs of eukaryotes and viruses. However both RNAs are U and A-rich in this region.


[Efficacy of plasma substitutes of different molecular weight in acute haemorrhagic shock in dogs (author's transl)]. Dogs were bled into haemorrhagic shock. They were then given isovolaemic infusions of dextran 60 and 40 and of hydroxyethyl starch with an average molecular weight of 200,000 and 40,000 respectively with a view of assessing the haemodynamic efficacy of these plasma substitutes. Solutions of high molecular weight hydroxyethyl starch (HES 400) were retained in the circulation for about the same length of time as was dextran 60. HES 40 (molecular weight 40,000) was retained for about 3-4 hours as measured by cardiac output. For normalizing a relative hypovolaemia, e.g. during anaesthesia or in some emergencies, colloidal plasma substitutes which will be retained for only a short time are entirely satisfactory.


[Cryoapplication in the field of ORL (author's transl)]. After drawing attention to the literature concerning the use of cryotherapy in the field of ORL, the results of this therapy based on 40 cases, involving a total of 73 applications, are set out. Of mucous membrane affections otherwise resistant to therapy and inclined to recidivation, it was possible to cure two thirds of the cases and achieved an improvement in five further cases, giving altogether more than three quarters of the cases showing favourable results. An appliance was used which achieved a temperature of -40 degrees C at the tip of the probe, using the Joule-Thomson principle with expansion of nitrous oxide. This temperature is sufficiently low to effect surface changes, but is not so low as to cause destruction of larger amounts of tissue. Cryotherapy should occupy a permanent place in medical practice.


Transfer of proteins from gels to diazobenzyloxymethyl-paper and detection with antisera: a method for studying antibody specificity and antigen structure. We describe a rapid and very sensitive method for detecting proteins as antigens after their separation in polyacrylamide/agarose composite gels, with or without sodium dodecyl sulfate. The polyacrylamide matrix is crosslinked with a reagent that can be cleaved with periodate or alkali to facilitate transfer of the protein bands to diazobenzyloxymethyl-paper, where they are coupled covalently. Specific proteins are detected by autoradiography after sequential incubation with unfractionated, unlabeled specific antiserum and 125I-labeled protein A from Staphylococcus aureus. Antibody and protein A can be removed with urea and 2-mercaptoethanol, and the same paper can be probed again with a different antiserum. An antiserum specific for the simian virus 40 virion proteins VP3 and VP2 has been prepared; it does not crossreact with VP1, as demonstrated by this method. An antiserum raised in rabbits against simian virus 40-transformed rabbit kidney cells is shown to be directed primarily against a periodate-sensitive moiety present in tumor (T) antigen from infected or transformed cells, whereas an antiserum raised in rabbits against large T antigen purified from lytically infected monkey kidney cells by electrophoresis in the presence of sodium dodecyl sulfate [Lane, D.P. & Robbins, A.K. (1978) Virology 87, 182-193] is directed primarily against determinants that are not sensitive to periodate.


Antigenic marker on a functional subpopulation of B cells, controlled by the I-A subregion of the H-2 complex. CBA/N mice have an X-linked recessive effect that results in the absence of a subpopulation of B cells carrying the Lyb3 surface marker. It has been shown previously that this marker is present on a mature subset of B cells in all mouse strains. In this paper the Lyb3+ B cell population in C57BL/6 mice was analyzed further. This subset of B cells selectively expresses a surface marker controlled by the I-A subregion of the H-2 complex. A cytotoxic antiserum recognizing this marker was raised by immunizing defective (CBA/N X C57BL/6)F1 male mice with C57BL/6 spleen cells. This antiserum also contained noncytotoxic, non-strain-restricted anti-Lyb3 antibodies. The possible functional relevance of this surface marker is discussed.


Definition of a unique cell surface antigen of mouse leukemia RL male 1 by cell-mediated cytotoxicity. BALB/c x-ray-induced leukemia RL male 1 is strongly immunogenic for (BALB/c x C57BL/6)F1 mice. Transplants of RL male 1 regressed after initial growth, and after tumor regression mice could resist repeated inocula of 10(7) RL male 1 cells. Spleen cells from immunized mice after in vitro stimulation with RL male 1 were cytotoxic for RL male 1 cells in 3-hr 51Cr assays. Pretreatment of immune spleen cells with Thy-1, Lyt-2, or Lyt-3 antisera and complement eliminated cytotoxic activity, indicating that effector cells for RL male 1 lysis are T cells. Tests with other target cells showed little or no cytotoxicity. Analysis of the specificity of T-cell killing of RL male 1 by competitive inhibition assays with unlabeled cells indicated that only RL male 1 could inhibit killing; other BALB/c tumors (13 x-ray or murine leukemia virus-induced leukemias and three myelomas) failed to inhibit lysis of RL male 1. A range of alloantisera and heteroantisera were tested for their capacity to block lytic activity in the absence of added complement. H-2d antisera and Lyt-2 and -3 antisera blocked lysis, the latter at the level of the effector cell. Antisera to other cell surface alloantigens, murine leukemia virus-related antigens, and immunoglobulins did not block RL male 1 lysis. Thus, T cells from mice immunized against RL male 1 recognize an individually distinct or unique antigen that does not appear to be related to any of the serologically defined cell surface determinants of RL male 1. In its restriction to a single leukemia, the RL male 1 antigen resembles the individually distinct antigens of chemically induced tumors and other tumor types of rodents.


Human glomerular visceral epithelial cells synthesize a basal lamina collagen in vitro. Isolated human glomeruli were digested with purified bacterial collagenase yielding epithelial cells. These cells grew to saturation density and did not become multi-layered. They were identified as visceral glomerular epithelial cells by their morphologic appearance by phase and electron microscopy and by the presence of surface receptors for C3b. Neither Factor VIII antigen nor Fc receptors were observed. The glomerular epithelial cells synthesized a collagenous protein that was antigenically similar to human glomerular basal lamina. Proteins precipitated from visceral epithelial cell medium with affinity purified antibody against noncollagenous glomerular basal lamina antigens yielded a single collagenase labile protein that by sodium dodecyl sulfate/polyacrylamide gel electrophoresis migrated with an apparent Mr of 168,000 in the presence of reducing agents. Analysis of hydroxyproline isomers yielded a ratio of 3-hydroxyproline to total hydroxyproline of 0.17. Pepsin digestion yielded a disulfide-bonded multimer which, with reduction, migrated with an apparent Mr of 148,000. These data demonstrate that human glomerular visceral epithelial cells can be isolated and propagated in vitro and that they synthesize a collagen similar to that found in vivo.


Cell-free synthesis and segregation of beta 2-microglobulin. beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized as a precursor with an NH2-terminal extension of 19 amino acids: Ser-X-Ser-Val-X-Leu-Val-Phe-Leu-Val-Leu-Val-Ser-Leu-X-Gly-Leu-Tyr-X. The processing and segregation of this peripheral membrane protein are directly comparable to those of secretory proteins and integral membrane proteins: addition of dog pancreas microsomal membranes during translation caused conversion to the processed chain, but addition of membranes after synthesis did not; only the processed chain sedimented with the membrane vesicles and was protected from proteolysis by the vesicles; and processing of nascent beta 2-microglobulin was blocked by competitive inhibitors that prevent processing and segregation of secretory and integral membrane proteins. These results suggest that the signal sequences of secretory proteins, integral membrane proteins, and peripheral membrane proteins have a common function and a common receptor on the cytoplasmic face of dog pancreas microsomal membranes. This system also provides a means for studying in vitro the expression and function of the major histocompatibility antigens that are associated with beta 2-microglobulin on cell surfaces.


Reverse transcriptase pauses at N2-methylguanine during in vitro transcription of Escherichia coli 16S ribosomal RNA. A restriction fragment strand complementary to a sequence near the 3' end of Escherichia coli 16S rRNA has been used to prime reverse transcriptase (avian myeloblastosis virus RNA-directed DNA nucleotidyltransferase; deoxynucleosidetriphosphate:DNA deoxynucleotidyltransferase, EC 2.7.7.7). In addition to transcripts that were extended to the 5' end of the RNA, two major transcription intermediates were observed. These discrete-sized cDNA intermediates are the result of a kinetic barrier imposed by monomethylation of the amino group on guanine that participates in base-pairing. Both major transcription intermediates correspond to attenuation at the known positions of N2-methylguanine (m2G) in the rRNA sequence. The relaxation time for elongation of the cDNA through m2G is approximately 3 min. No other major kinetic pauses were observed in the 1340 bases transcribed.


Heavy chain of HLA-A and HLA-B antigens is conformationally labile: a possible role for beta 2-microglobulin. The three-dimensional organization of HLA antigens has been investigated by spectroscopic and immunochemical techniques. Measurement of the circular dichroism shows that in papain-solubilized HLA the heavy chain as well as the previously studied light chain (beta 2-microglobulin) consists predominantly of beta-pleated sheet structures. When heavy chain is separated from the light chain under denaturing conditions and is allowed to renature, about 50% of the beta structure is lost, concomitantly with most of the alloantigenic activity. Analysis of the two acid-cleaved fragments of HLA-B7 heavy chain shows that beta structure is preferentially lost from the COOH-terminal region of the heavy chain. Exposure to denaturants per se does not inevitably result in irreversible loss of antigenic activity. However, recovery of antigenic properties does seem to depend on reassociation of the two chains. The results reported here provide further evidence for (i) the similarity of HLA antigens and immunoglobulins at the three-dimensional level and (ii) two distinct and physiologically important conformations of the HLA heavy chain, depending upon whether it is associated with the light chain.


Induction, establishment in vitro, and characterization of functional, antigen-specific, carrier-primed murine T-cell lymphomas. T cells were isolated from spleens of C57BL/Ka/Thy 1.1/Lb mice immunized with 2,4-dinitrophenylated keyhole limpet hemocyanin (DNP-KLH). The mice were infected in vitro with radiation leukemia virus and injected intrathymically into congenic C57BL/Ka (Thy 1.2) recipients. Within 3-4 months, seven thymic lymphomas developed, five of which were of donor type. The donor lymphomas were explanted and permanent cell lines were established in vitro. These lymphoma cells are capable of providing antigen-specific carrier (KLH)-primed help to DNP-primed B lymphocytes in secondary antibody production to DNP-KLH. They also enhance the secondary antibody response of whole period spleen cell populations to DNP-KLH. The availability of these immortal clonable populations of immunofunctional neoplastic T lymphocytes should facilitate biological and biochemical investigations of lymphocyte interactions during synthesis of antibody to thymus-dependent antigens.


Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin. The murine antibody and T lymphocyte proliferative responses to sperm whale myoglobin (Mb) were found to be under control of two distinct H-2-linked immune response (Ir) genes (Ir-Mb-1, mapping in the I-A subregion, and Ir-Mb-2, mapping in I-C). H-2(d) mice (B10.D2 and DBA/2), with both genes, were high responders to Mb and its fragments for both antibody secretion and T cell proliferation, while H-2(b) (B10) and H-2(k) (B10.BR) mice were low responders. Strains with only Ir-Mb-2 [B10.A and B10.A(5R)], which were intermediate responders to Mb, made antibodies to and proliferated in response to the NH(2)-terminal fragment (1-55) but not the COOH-terminal fragment (132-153) when immunized with Mb. In contrast, mice carrying only the Ir-Mb-1 gene (D2.GD and B10.GD) made antibodies to and proliferated in response to both fragments. However, their proliferation to fragment (1-55) was often lower than that of their congenic high responders (DBA/2 and B10.D2, respectively), possibly because they respond to only some of the determinants on this NH(2)-terminal fragment. Thus, these data demonstrate that distinct Ir genes, mapping in separate I-subregions of H-2, control responses to different antigenic determinants on the same protein molecule. Moreover, the gene that controls the T lymphocyte responses to a given determinant also controls production of antibodies specific for that same determinant (or a closely associated one).


Non-H-2 antigens on fibroblasts and an embryocarcinoma cell line react with xenoantisera against H-2 antigens. The murine embryocarcinoma cell line F9 lacks the classical transplantation antigens. However, rabbit anti-H-2 antigen sera, recognizing "backbone structures" of H-2 K and D antigens, react with three types of molecules manufactured by F9 cells. A 49,000- and a 25,000-dalton chain are glycoproteins located on the cell surface. The third component with an apparent molecular weight of 15,000, and the 25,000-dalton chain seem to be unrelated to the 49,000-dalton glycoprotein. The 25,000- and 15,000-dalton components are not manufactured by splenocytes, thymocytes, hepatocytes, or various lymphoma, mastocytoma, and plasmacytoma cell lines. However, fibroblasts derived from both embryos and adult animals synthesize 25,000- and 15,000-dalton molecules reactive with the rabbit anti-H-2 antigen sera. The 49,000-, 25,000-, and 15,000-dalton molecules are not recognized by a syngeneic anti-F9 cell serum.


Thymus-derived lymphocytes control the expression of immunogenic properties of peritoneal macrophages. Macrophages, given keyhole limpet hemocyanin in vitro, from normal mice initiate in culture antigen-specific T cell-mediated immune reactions. On the other hand, macrophages from nude, from adult-thymectomized, or from neonatal-thymectomized mice are impaired with respect to their capacity to signal such an antigen-specific T cell reaction. Thymocytes from hydrocortisone-treated donors, added in culture to such impaired macrophages, rendered them immunologically potent. The capacity of macrophages from adult thymectomized mice to promote the activation of antigen-specific "helper" T cells which, cooperating with B lymphocytes, would lead to antibody production, was also impaired. Thus, it appears that short-lived T lymphocytes control the maturation of macrophages up to a stage at which they can present antigen-specific T cells with antigen in an immunogenic form. We found that such T lymphocytes also control the phagocytic properties of macrophages, yet the impairment of their immunogenic properties does not seem to be derived from decreased phagocytosis.


Immune response genes have a variable influence on the selection of antigenic foreign and self determinants of insulin. We studied the proliferative response of mouse T lymphocytes to determinants on ungulate insulins. The immunopotency of defined determinants on the molecule was found to be regulated by three factors: the immune response genes of the immunized mouse, the mode of presentation of insulin on cells or in adjuvant, and the intramolecular cooperativity between different determinants on the insulin molecule. Autosensitization against self determinants was observed under specific conditions. These findings emphasize the variable expression of immune response genes.


Moderately raised blood lead levels in children. There is no doubt that high blood lead levels are associated with mental subnormality and hyperactivity. Several recent studies in Britain and America have investigated the relation between moderate levels, i.e. between 20 and 40 microgram/100 ml and behavioural and cognitive phenomena. Epidemiological studies have generally failed to point to a clearcut relation between such levels and overactivity or decrements in performance on standard intelligence and educational tests. Published studies with the use of chelation techniques have suffered from methodological weaknesses. It is known that socio-economic factors are powerfully related to measured intelligence and behaviour and, on the evidence available, it is to them that attention should primarily be given if preventative measures are being considered. There remains the possibility that more refined test measures would detect impaired functioning in children with moderately raised lead levels, and that there is an interaction effect between lead and host resistance.


[The diagnostic value of double-contrast-technique cystography in the evaluation of benign and malignant lesions of the urinary bladder (author's transl)]. Cystography by double-contrast-technique as a simple and quick method of evaluating benign and malignant lesions of the urinary bladder is being described. 301 examinations were reviewed and are being discussed in regard to diagnostic value, indication, complication and radiation exposure of this method. A few typical cases are being demonstrated to illustrate the value of this method in the spectrum of other diagnostic methods in the work-up of urinary bladder lesions.


[Difficulties and errors in the treatment of cancer of the prostate]. On the basis of personal experience and of data in the specialized literature, the author supports the complex treatment of prostatic cancer, by radiation, surgery and hormones. Castration should be performed from the beginning. Neither should the advanced stages of the disease be abandoned because total prostato-vesiculo-cystectomy, followed by radiation therapy of pelvic lymph-nodes and hormone administration may still have encouraging results.


[Study of simultaneous dosage of carcino-embryonic antigen (C.E.A.) and beta 2-microglobulin in serum and pleural liquid (author's transl)]. Simultaneous dosage of carcino-embryonic antigen and beta 2-microglobulin was studied in serum and pleural liquid. Among the 20 patients with non-neoplasic infections, the carcino-embryonic antigen was not increased in the serum and only once at a border-line level in the pleura. The level of beta 2-microglobulin seems to be related to the number of lymphocytes in the pleural liquid (increase in 45% of the cases compared to 20% in the serum). Among the 31 cancer patients, carcino-embryonic antigen is increased in the serum of 36% of the cases and in the pleura of 48%. In 5 observations, the pleural levels were considerably increased compared with serum levels, suggesting the existence of a pleural metastasis. The beta 2-microglobulin is elevated in only 26% of the cases in the pleural liquid and in 13% in the serum. At the present state of knowledge, it therefore seems unnecessary to continue investigations concerning the beta 2-microglobulin. On the contrary, the pleural dosage of carcinoembryonic antigen could contribute to the diagnosis.


[Pleural mesothelioma: morphology, histochemistry, difficulties in diagnosis and nosologic problems (author's transl)]. Using the material of the French Register, these authors define the epithelial aspects and the histological forms of diffuse pleural mesothelioma. Histochemistry studies, on pleural cytology and on tissues, are of the utmost importance in distinguishing mestothelioma from carcinoma. Hyaluronic acid is almost always showed in the epithelial mesothelioma, being otherwise only noticed in some very flourishing forms of mesothelial cell hyperplasia nad in rare mucus-secreting carcinoma. Cytoenzymology studies are very useful on pleural fluid material, making it possible to show the difference between macrophages and mesothelial cells. Difficulties encountered by pathologists are analysed with reference to the materials examined: cytology, needle biopsy, guided biopsies, surgical material and documents from autopsies. After a critical study of the structures seen in other pleural tumors mesothelioma is defined as a localized or diffuse tumor of the pleura, positively originating from mesothelial cells which manifest either epithelial structures of a double epithelial and mesenchymal composition.


Measurement of antihaemophilic factor A antigen (VII:CAg) with a solid phase immunoradiometric method based on homologous non-haemophilic antibodies. Antihaemophilic-factor-A-antibodies, which had spontaneously arisen in 2 patients, were used to develop an immunoradiometric method for measurement of antihaemophilic factor A antigen (VIII:CAg). 13 patients with severe haemophilia A had VII:CAg below the limit of detection (0.01 U/ml). Patients with moderate and mild haemophilia A either had VII:CAg roughly equal to factor VIII clotting activity (VIII:C) or a not detectable VII:CAg, suggesting 2 different molecular mechanisms in moderate and mild haemophilia A. VIII:CAg could be detected in serum but in lower amounts than in plasma. In 2 patients with von Willebrand's disease VIII:CAg equalled VII:C. The post-transfusional retarded increase of VII:C in 1 patient with von Willebrand's disease was accompanied by a slight increase in VIII:CAg. Fetal plasma contained measurable amounts of VII:CAg.


Histochemical study of orcein-positive hepatocellular material in paraffin sections of liver biopsy samples in the course of various liver diseases. A histochemical study was carried out on orcein-positive hepatocellular material in 111 cases, 27 of which were stained positively by orcein. Orcein-positive material was very frequently found in protracted viral hepatitis and in chronic active hepatitis, as well as in other liver diseases with or without cholestasis; it was absent in liver cirrhosis. In all the cases considered the orcein-positive material was mainly formed of proteins, rich in amino acids with sulfhydryl and disulphide radicals, tryptophan and, to a lesser extent, of NH2 alpha amino acids. The orcein-positive substance was apparently carbohydrate-free. The presence of copper was also confirmed.


Disopyramide--an effective treatment for lignocaine resistant ventricular dysrhythmias. Intravenous disopyramide was used in 13 patients who developed recurrent ventricular dysrhythmias despite initial treatment with intravenous lignocaine after admission to the Coronary Care Unit of a busy district hospital. This was effective in 8 of the 13 patients treated and there was no major side effects observed. Disopyramide has the advantage of being available both as an oral and an intravenous preparation and is a useful drug to be added to the list of more conventional anti-dysrhythmic agents.


Circular forms of DNA synthesized by Rous sarcoma virus in vitro. Electron microscopic analysis of the DNA product synthesized by detergent-disrupted preparations of Rous sarcoma virus in vitro revealed the presence of several interesting molecular forms including covalently closed circular DNA. The identification of such circular DNA indicates that virions of retroviruses contain all the components necessary to facilitate the complete synthesis of mature forms of viral DNA and therefore provide a useful system to delineate the molecular mechanisms involved in their synthesis.


Polymorphism of the BoLA system.

Polymorphism of the BoLA system. The bovine lymphocyte antigen system (BoLA) was studied by serological methods. Evidence for the existence of one locus was established and six codominant alleles were found to segregate at this first locus. The frequency varied considerably among these genes, and the presence of a null allele suggests that new BoLA specificities are likely to be found in the cattle population.


The structure and evolution of the HLA--Bw4 and Bw6 antigens. The HLA--Bw4 and Bw6 antigenic determinants have been shown to co-migrate with HLA--B determinants on gel-filtration, sucrose density gradient centrifugation and affinity chromatography, using Lens culinaris lectin and antibody against human beta 2 microbulin. These and other published data imply that the HLA--Bw4 and Bw6 determinants reside on the same polypeptide chain as other HLA--B locus determinants. The implications of this in terms of the evolution of cross reacting groups of antigens at the HLA--B locus are discussed.


The association of HLA--B8 with atrophic thyroiditis. One-hundred-and-forty-seven patients with autoimmune thyroiditis were studied with respect to HLA antigens as they related to various clinical features. HLA--B8 was found to be significantly increased among 59 patients with atrophic thyroiditis (57% vs. 26% for controls) but was identical to controls in 88 patients with goitrous thyroiditis (26%). No relation was found in either group between B8 and thyroid autoantibody titer or, in the case of goitrous thyroiditis, the rate of progression of the disease. Thus a link seems to be established between Graves' disease and atrophic thyroiditis in that both are significantly associated with HLA-B8. This study stresses the need to take clinical features into consideration when examining for HLA/disease associations.


Increased frequency of HLA--DRw2 and DRw3 in multiple sclerosis. Previous studies of multiple sclerosis patients showed the existence of a positive association between multiple sclerosis and HLA--A3 and --B7, as well as a negative association with B12. These observations have been confirmed. In addition, a more marked association has been observed with two recently identified B-cell antigens, DRw2 and DRw3, closely related to the HLA--D locus. The presence of cold lymphocytotoxic antibodies was found to bear no relationship with those two specificities. These results suggest that two genes of the HLA--DR region may play a role in the pathogenesis of multiple sclerosis.


Detection of B-cell-specific alloantibodies in pregnancy sera in the lymphocytotoxicity and the indirect immunofluorescence techniques. Two hundred and eight pregnancy sera were tested for the presence of antibodies specific for lymphocyte sub-populations by using the isolated B and T lymphocytes from the women's mating partners. This was done by the microlymphocytotoxicity and the indirect immunofluorescence techniques. Five sera (2.5%) reacted exclusively with B lymphocytes and sixty-three sera (30.2%) reacted with both B and T lymphocytes; none of the sera was specific for T cells. Several sera, reacting with both B and T lymphocytes, were absorbed with platelets and this procedure revealed nine additional antiseraa specific for B lymphocyte antigens. Specificity studies on a panel of forty-eight HLA-ABCD typed individuals indicated that most antisera possibly defined new B-cell antigens. Family studies established that the antigens defined by these antiser were coded for by genes in the Major Histocompatibility Complex.


HLA determinants in idiopathic hemochromatosis. HLA-A and B antigens were defined in 154 unrelated idiopathic hemochromatosis patients. The study confirmed the highly significant positive association with HLA antigens A3 (corrected P less than 10(-10)) and B14 (corrected P less than 10(-9)). HLA-DR typing showed increased frequency of the specificity DRw6, which was frequently associated with the phenotype A3, B14 and antigen B14, suggesting linkage disequilibrium. This was borne out by PLT data.


The specificity of secondary MLC assayed by titration of primed lymphocyte populations. The specificity of responses in secondary MLC was studied by titration (100 x 10(3) to 5 x 10(3)) of responder primed lymphocytes. In all instances, significant proliferative responses of responder primed lymphocytes to the specific stimulator occurred using lower responding cell numbers. When tested against allogeneic stimulating donors, three patterns of responses were observed: no significant responses, responses only at higher (100 x 10(3)) responding cell densities, and responses at lower responding cell densities, similar to those with the priming donor. In instances where primed lymphocytes responded significantly to allogeneic stimulating cells at lower cell densities, the responses were considered positive and the stimulating cells positive for the PL determinant. In several instances, primed lymphocytes responded significantly to allogeneic stimulators negative for the specific HLA-D and/or HLA-DR specificities. On the other hand, in experiments where allogeneic stimulating donors shared either HLA-D or DR specificity with the priming donor, a significant response was always observed. Thus, the PL determinant was present on stimulating allogeneic cells negative for specific HLA-D and DR specificities. The present data suggest that an analysis of the specificity of primed populations could be profoundly affected by the responder cell density at which the assay is performed. Also, the data suggest that other MHC determinants, including non-HLA loci may be important in secondary MLC.


On the heterogeneity of B40.

On the heterogeneity of B40. Evidence is presented for the heterogeneity of HLA-B40. At least two sub-groups can be recognized: Bw40.1 which is Cw3 associated and Bw40.2 which is Cw2 associated in Caucasians, but not in other populations. The recognition of Bw41 (Sabell), Bw47 (407*), and Bw48 (KSO) with both local Bw40 antisera and sera from the 7th Histocompatibility Workshop is discussed.


A new HLA-B antigen (HOK-1) found in the Japanese. The HLA-B8 antigen is one of the characteristic antigens associated with organ specific autoimmune diseases among Caucasians. Among the Japanese, HLA-B8 positives have been assumed to be extremely rare. By using some HLA-B8 typing sera, a new HLA-B antigen, HLA-Bw4 positive, was found in the Japanese. This new HLA-B antigen, tentatively called HOK-1, showed a phenotype frequency of 3.7% and a gene frequency of 1.9 +/- 0.6%. This antigen has a strong linkage disequilibrium with HLA-Cw1 among the Japanese.


A simulation of HLA-DR matching in kidney transplantation. A simulation of the matching for HLA-DR, B, A loci was achieved by taking into account the practical situation of kidney transplants for 89 donors and 322 potential recipients. A complete HLA-DR identical graft was theoretically possible in 52% of the cases. Conversely, if the identity for B or particularly the identities for both B and A were sought, the necessary pool of recipients would have to be much larger, requiring intense international cooperation.


The frequency of HLA-Dw1 determinant in subacute (de Quervain's) thyroiditis. Investigation of a group of 23 patients suffering from subacute (de Quervain's) thyroiditis for the frequency of the HLA-Dw1 determinant showed this determinatant to be more frequent--30.4%--compared to its frequency in a healthy population--19.1%. The finding is not statistically significant.


Identification of an antigen shared by mouse liver and lung. In response to multiple injections of liver extract from Balb/c mice, DBA/1 mice produce antibodies against a component of the liver preparation which is not F-antigen, but which is able to precipitate in gel diffusion tests. This antigen is also found in extracts of Balb/c lung, but not in a variety of other organs tested. Liver extracts from all of the inbred strains studied contain the antigen, except extracts from DBA/1 mice. Furthermore, this antigen was not found in the liver or lungs of other vertebrates tested. The antigen has been designated antigen-L1.


HLA-DR antigens in Black North-Americans and their association with HLA-D. A random population of 108 Black North-Americans, 79 of whom had also been typed for HLA-D in Mixed Leukocyte Culture (MLC), were serologically tested for DRw with Seventh International Histocompatibility Workshop trays. Clusters of B cell alloantisera were identified which defined several DRw antigens. Although the clusters for DRw1, DRw2, DRw3 and DRw7 showed similarities with the clusters derived during the Seventh International Histocompatibility Workshop, distinct differences were observed which should be taken into account for the assignment of the DRw antigens in Blacks. DRw6 was defined by a cluster of sera which also reacted with DRw1 and DRw2 cells. The tails of these sera were used to assign DRw6, but this was only possible with DRw1 and DRw2 negative cells. It was not possible to identify serum clusters specific for DRw4 or WIA8. The associations between DRw and the corresponding Dw specificities were reasonably good for DRw1, DRw2 and DRw7, but weaker for DRw3 and DRw5. The cumulative gene frequencies for DRw1, DRw2, DRw3, DRw5, DRw6 and DRw7 was 0.86. The frequencies of these six DRw antigens fitted into a Hardy-Weinberg distribution, suggesting that DRw in Blacks is controlled by a single gene with multiple alleles.


HLA antigens in a Scottish psoriatic population. Sixty-one patients in the Dundee area suffering from psoriasis were typed for HLA-A and HLA-B antigens. On the basis of the typing results, the patients were divided into three groups, and studied with respect to sex, age of onset and familial incidence of the disease. The frequency of HLA-A1 appeared to be increased and HLA-B7 decreased but HLA-B13 and HLA-B17 were highly significantly increased (P less than 10(-6) and P less than 10(-10) respectively) in the psoriatic group compared to 204 controls. Of particular interest was a highly significant association of HLA-A1 with HLA-B17 in psoriatic patients. Family studies showed HLA-B17 to be a useful genetic marker for psoriasis in the families of B17 positive patients. Considerations of age of onset, familial incidence and typing data suggest that there is heterogeneity of genetic susceptibility to psoriasis and that one probable mechanism is the dominant inheritance of a "disease allele" in linkage disequilibrium with the allele coding for HLA-B17.


HLA-A and B antigen frequencies in Welsh coalworkers with pneumoconiosis and Caplan's syndrome. HLA typing was performed on 267 Welsh coalworkers with pneumoconiosis (96 cases of simple pneumoconiosis, 115 cases of progressive massive fibrosis and 56 cases of Caplan's Syndrome) and 134 coalworkers with no abnormality. The presence or absence of rheumatoid factor was also determined. The results fail to confirm a previously reported increase in HLA-A1 and B18 in coalworkers with no pneumoconiosis. When correction was made for the number of antigens typed (i) HLA-Bw21 was significantly increased from 1.1% in the total group with pneumoconiosis to 8.2% in coalworkers with no abnormality (P corrected less than 0.032); (ii) HLA-Bw45 was increased in Caplan's Syndrome (10.7%) and Caplan's Syndrome patients with rheumatoid factor (16.1%) when compared to a non-occupationally exposed control group (0.8%) (P corrected = 0.019 and 0.0064 respectively). These results were not significant when comparisons were made with the coalworker group with no abnormality. The apparent higher frequency of Bw45 in Welsh coalworkers is discussed.


Evidence for an HLA-linked resistance gene in Buerger's disease. The incidence of Thromboangiitis Obliterans in brothers and the high prevalence in some ethnic groups have led us to investigate the histocompatibility HLA-A, B and DR antigens of 46 Buerger's disease patients. The main result indicates a marked decreased freqeuncy of the B12 antigen: 2.2% vs 28% in controls. Our study suggests that Buerger's disease is, on the basis of HLA antigens, a distinct immunogenetic entity and not a particular form of arteriosclerosis. Moreover, this disorder may represent a clue to the existence of resistance genes linked to HLA.


Qualitative and quantitative evaluation of indirect immunofluorescent H-2 stain on tissue sections. We have utilized H-2 specific antisera from congenic resistant donor recipient combinations to localize H-2 antigens in tissue sections using the indirect immunofluorescent technique. H-2 specific immunofluorescence is observed in spleen, kidney, and liver sections: however, especially with liver sections, there are cases in which the expected specific stain is weak or absent. In addition to microscopic evaluation by eye, we have employed a microscope attached photometer; recordings from this instrument differentiate positive from control stained spleen sections.


Strong linkage disequilibrium between HLA-Dw2 and and BfS in multiple sclerosis and in the normal population. An increased frequency of the S allele of Properdin factor B (BfS) was found amongst 162 patients with multiple sclerosis (MS) compared with 470 normal controls. This increase was shown to be due to a strong linkage disequilibrium (LD) between BfS and HLA-Dw2 in 77 patients typed for both systems (delta = 3.84%, P = .0002). The same LD was demonstrated amongst 100 normal controls (delta = 2.24%, P = .0049) and 31 patients with idiopathic demyelination of the peripheral nervous system (IDPN). A total of 70 haplotypes with HLA-Dw2 were encountered (40 MS, seven IDPN and 23 normal controls) and all contained BfS. In the MS patient group, a much weaker association was noted between BfS and HLA-B7 suggesting either that the Bf locus is musch closer to the HLA-D than the HLA-B locus or (and) that HLA-D and Bf products selectively interact (perhaps on the surface of B lymphocytes) with evolutionary advantage or disadvantage resulting from certain allelic combinations. Strong associations between BfS1 and HLA-Bw21 (P = .0000) and BfF1 and HLA-B18 (P = .0001), both previously reported, were confirmed in the current study. No increase in the frequency of a glyoxalase (GLO) allele was found amongst the MS patients and no LD was encountered between HLA-Dw2 and a GLO allele. The possibility that the HLA-Dw2, BfS disequilibrium has resulted from a selective advantage conferred on the general community but at the expense of increasing susceptibility to MS should be considered.


The quantitative histochemistry of ribonucleic acid using gallocyanin. A method for the cytophotometric estimation of ribonucleic acid in tissue sections using gallocyanin-chrome alum is described. The dye obeys Beer's law in gelatin sections. The effect of deoxyribonuclease on the staining of ribonucleic acid is also investigated. The results indicate that this method is of value in the quantitation of ribonucleic acid.


Combined stain for fish pituitary.

Combined stain for fish pituitary. A new combined stain is described for the study of cell types in the fish pituitary. Tissues are prepared by fixing in formol-sublimate and then embedded in paraffin wax. Tissue is sectioned at 5 micron and than stained sequentially with performic acid-alcian blue, periodic acid-Schiff, orange G, and acid fuchsin. As a result of this procedure acidophils stain as follows: lactotropes, red; corticotropes, light pink; melanotropes, bright pink; and somatotropes, orange. Cyanophils stain either magenta red (gonadotropes) or blue (thyrotropes). Neurosecretory material and the fibers of the pars nervosa which penetrate the pars intermedia stain light blue.


A rapid silver impregnation method for nervous tissue: a modified protargol-peroxide technic. A rapid, reliable silver impregnation method is described for nervous tissue fixed in formol-saline, Bouin or Susa. Sections are impregnated for 10-15 minutes at room temperature or 37 C in a solution containing 0.5 g Protargol-S, 0.005-0.01 g allantoin, 1 ml of 1% Cu[NO3]2, 1 ml of 1% AgNO3, and 1-2 drops of 30% H2O2 in 100 ml distilled water. Thereafter the sections are reduced in a hydroquinone-formalin solution. This is followed by gold toning and subsequent reduction and mounting. Alternatively, following the first reduction, the silver image can be intensified by placing sections in a silver-allantoin bath which is followed by reduction and mounting. This method is very reliable and selective, making it suitable for general routine and research use.


Displacement.

Displacement. Displacement is a noncommital term for the reactions that occur when slides previously stained in phloxine or rose Bengal are immersed for varying lengths of time in a solution of another dye in ethyl Cellosolve. In most histotechnic texts Lendrum's (1947) phloxine-tartrazine is given as the stain for acidophilic inclusion bodies. However the lack between the phloxine and tartrazine has been a serious limitation. A number of dyes were tried as possible substitutes for the tartrazine. A rose Bengal-Bismark brown Y procedure was developed which stains similarly to Lendrum's phloxine-tartrazine and which does have the needed contrast. After staining for 10 min in 1% aqueous rose Bengal and rinsing in isopropyl alcohol slides are placed for 20, 30, 40 and 50 min in 0.05% Bismark brown Y in ethyl Cellosolve. In various tissues and structures the rose Bengal is sequentially displaced by the Bismark brown Y. Thus collagen loses the red stain after 30 min while acedophilic structures like sperm heads and Paneth cell granules retain the red stain after 50 min in the displacement solution. The results are strikingly similar to staining with alkaline Biebrich scarlet.


A new method of urinary stone analysis by batik histochemical staining of thin sections. Thin sections of urinary calculi are prepared by petrographic methods using Araldite as the mounting medium. By covering the remaining part of the section with wax, an exposed segment of the section is stained by a histochemical technique. By the process of dewaxing and rewaxing, successive adjacent segments are stained by GBHA, Von Kossa, Schultz, and titan yellow methods for calcium oxalate, apatite, uric acid and urates, and magnesium in magnesium ammonium phosphate, respectively. If desired, matrix in additional segments is stained with PAS and aqueous toluidine blue. Microscopic examination of each layer through all the stained segments of a stone section reveals its chemical nature. Thus the chemical composition, morphology, and spatial distribution of the crystalline and matrix constituents of thin sections of urinary calculi are simultaneously revealed in situ.


Feulgen, iron-propionocarmine and cupra-ammonium in preparing algal chromosomes for light microscopy. A method for obtaining algal chromosomal preparations is described employing the Feulgen method for DNA staining, Fe-propionocarmine as an enhancing stain, and cupra-ammonium to remove cell wall material. Fe-propionocarmine applied as a gradient to the side provides cells stained with the Feulgen stain alone or with the Feulgen Fe-propionocarmine stain, thereby facilitating useful comparison. Where dilute the Fe-propionocarmine enhances nuclear staining without staining orthe organelles; where more concentration it also stains the nucleolus, spindle, spindle polar bodies, pyrenoid and protoplast. Treatment with cupra-ammonium, to remove polysaccharide wall material, followed by neutralization with propionocarmine, enables thinner squashes and better chromosome spreads without loss of differential staining. Preparations mounted in euparal are long-lasting.


Selective vital staining of companion cells of potato tuber and parsnip root with neutral red. When staining the internal phloem region of a potato tuber with the vital stain neutral red, it was observed that files of elongated cells of narrow diameter were heavily stained and were easily distinguishable from the more isodiametric parenchyma cells, many of which did not stain with neutral red. The elongated cells were identified as companion cells by locating the adjacent sieve-tube members through counterstaining with aniline blue and reviewing under violet light. Of a number of other plants surveyed, only parsnip roots possessed companion cells exhibiting a similar slective staining. In other plants both the companion cells and the surrounding parenchyma cells usually stained. Sieve-tube members never accumulated neutral red. It was concluded that the vacuoles of the companion cells of the potato tuber were stained by the ion trap mechanism because of the color of the accumulated stain, the lack of staining when neutral red was applied in an acidic solution, and the complete destaining after soaking in dilute ammonium hydroxide.


Stabilized Romanowsky blood stain.

Stabilized Romanowsky blood stain. It has been shown that the degradation of thiazine dyes which normally occurs in methanolic solution, as in the case of Romanowsky blood stains, can be prevented by making the solution acidic. In a certain range of acidity, the stain precipitates in the form of monothiazine eosinate, but by making the solution sufficiently acidic, eosin is protonated and the precipitate cannot form. These observations have been used to develop a blood stain which is stable, even at elevated temperatures, for several months. For use the stain is neutralized by a specially formulated fixative solution.


Simple method for visualization of the islets in fixed but otherwise intact pancreas. A simple, inexpensive, reproducible method is described for prominently displaying the islets of Langerhans. The method consists of sequential arterial perfusion of the organ of the sacrificed animal with saline, formalin, hematoxylin, and water, followed by clearing in methyl salicylate. The procedure should be useful whenever islet tissue needs to be quantitatively distinquished from non islet tissue and fixation is allowable.


[Control of the success of radiotherapy in case of mastocarcinomas by means of mammography (author's transl)]. The authors present the experience about modifications of the mammographic data caused by X-ray irradiations which are described in three publications of other authors. Then they mention a first case observed by themselves in 1953 and give a detailed description and documentation of a new observation. In these cases and contrary to the reports of the other authors, a total regression of the tumor shadow in the radiogram was found. The first patient had demonstratable pulmonary metastases already when she was irradiated and the new patient died of cachexia. Before she died, metastases of the vertebral column were demonstrated by radiography which, according to the general and clinical findings, had certainly already existed at the beginning of radiotherapy. It had not been possible to find out what was the nature of pasty swellings lying near the tumor which had not been visible on the radiogram.


[Therapy with gestagens for gynecological tumors sensitive to hormones (author's transl)]. Our method of irradiation of the endometrial carcinoma is described. The patient collective concerned represents a negative selection, as only inoperable cases with an endometrial carcinoma undergo primary irradiation. The 5-year survival rate amounted to 50.4% of 802 patients in the period from 1950 through 1970. Additional therapy with gestagens is discussed and recommended. The histological alterations in the material obtained by so-called "second-look curettages" are reported. Application of gestagens to other hormonesensitive tumors such as carcinoma of the ovary or adenocarcinoma of the cervix uteri is considered.


[Clinical and roentgenological findings after radiation therapy of malignant esophageal tumors (author's transl)]. The palliative effect of treatment stands in the first place in radiation therapy of the esophageal carcinoma. Clinical and roentgenolocical features before and after radiation therapy are reported for 172 patients having been treated under high-voltage conditions between 1962 and 1977. The response of the tumor to irradiation is largely dependent on the tumor shape as visible in the radiograph. In case of tumors growing in polypous shape, often a regression of the tumor is observed even after low doses. An effect beginning later but frequently lasting for a longer time is found with tumors of circular stenosing and diffusely infiltrating growth. All in all a temporary dilatation of the tumor stenosis was achieved in 52% of the patients. Serious side effects of the radiation treatment rarely were observed.


Detection of non-HLA antigens: effect of lymphocyte priming and amplification signals. We studied three potential mechanisms that might account for the difficulty in detecting non-HLA antigenic disparities between HLA-identical siblings: (1) a low frequency of antigen-reactive cells; (2) the failure of antigen recognition to trigger proliferation or cytotoxicity; and (3) the development of suppressor cells or factors. In vitro sensitization was used to increase the frequency of antigen-reactive cells. Allogeneic lymphocytes or supernatants from mixed lymphocyte cultures were used to provide nonspecific proliferative signals. Neither approach was successful in facilitating the detection of proliferation or cytotoxicity between HLA-identical siblings. Furthermore, we found no evidence for the development of antigen-specific suppressor cells or factors. These data indicate that other mechanisms must underlie the difficulty in detecting non-HLA antigens in vitro.


Further characterization of immunological unresponsiveness induced in mice by ultraviolet radiation. Growth and induction of nonultraviolet-induced tumors in ultraviolet-irradiated mice. Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.


Enhanced effectiveness of adriamycin and bleomycin combined with local hyperthermia in neck node metastases from head and neck cancers. The results of this study concern the comparison of the clinical effects of adriamycin (ADM) or bleomycin (BLM) alone and combined with local hyperthermia on 15 patients with multiple (29) neck node metastases from head and neck cancers. With repeated low fractional daily doses of drug a significant though transient tumor regression was obtained in 2/8 and in 3/6 of the lesions treated with ADM or BLM alone, respectively. When the drugs were combined with 42-43 degrees C hyperthermia, an overall response, either complete or partial, was seen in all the lesions. Complete regression was observed in 38% (3/8) and 43% (3/7) of the lesions treated with ADM or BLM, respectively, combined with heat. At a 4-month follow-up, 33% (2/6) and 40% (2/5) of the same groups of lesions remained still undetectable. These results suggest that the combined treatment of drugs and local hyperthermia can be advantageously employed in clinical practice for treating local tumors, especially recurrences in previously irradiated areas.


Serum proteins in prostatic cancer. IV. Alterations and clinical response following cryoprostatectomy. Evaluation of alterations in the level of the five major electrophoretic fractions of serum proteins (albumin, alpha 1-, alpha 2-, beta- and gamma-globulin) in 18 patients with prostatic cancer prior to and following cryoprostatectomy disclosed: (i) a progressive increase in the level of alpha 2- and beta-globulin and the incidence of patients possessing statistically significant (p less than 0.05) elevations in these proteins with a progression of the stage of their malignancy; (ii) a significant decrease in albumin, alpha 2- and beta-globulin and increase in alpha 1- and gamma-globulin from their preoperative levels following cryoprostatectomy in patients with metastatic disease (stage III) in association with a favorable clinical response; (iii) an overall significant decrease in albumin and alpha 2-globulin and increase in alpha 1-globulin from their preoperative levels and (iv) a general association of decreases in albumin (83% of the patients) and alpha 2-globulin (92%) and gamma-globulin (75%) with a favorable clinical response following cryoprostatectomy. Limited to study of a small patient population, the present results confirm earlier studies suggestive of a prognostic potential for alpha 2-globulin, as applied to stage identification in prostatic cancer once the initial diagnosis has been made. Pending confirmation and evaluation of a larger patient population, the observed alterations in serum protein, while not pathognomonic for prostatic cancer, and alterations of inhibitory ('immunoregulatory') factors, may provide adjunctive criteria for monitoring the clinical response following cryoprostatectomy.


Incidence of prostatic calcification in blacks in Washington, D.C., and selected African cities. Correlation of specimen roentgenographs and pathologic findings. Cooperative Prostatic Research Group. The incidence of calcification in the prostate gland of black men from Washington, D.C., and from Ibadan, Nigeria, and Accra, Ghana, West Africa, was assessed in a total of 874 consecutive, unselected prostate specimens removed at autopsy during a five-year period (1973--1978). In the combined series there was a significant positive association between prostatic calcification and age (p less than 0.001). The frequency of calcification was significantly higher in the Washington, D.C. series than in the West African series at all age levels (p less than 0.001). This difference most likely reflects the different dietary patterns of the two population groups.


[Synchronization of estrus in heifers using Chlorsuperlutin (CSL) vaginal tampons]. A pilot experiment with heifer heat synchronization with chlorsuperlutin-soked intravaginal tampons was conducted with 254 heifers in six herds in the North Moravian region. The rubber-foam tampons, cylindrical in shape (diameter 70 mm, height 70-90 mm), were introduced into the cranial part of the vagina, using an applicator and a vaginal speculum. Sixteen days after introduction, the tampons were removed by pulling the silon thread with which the tampons were cross-stitched. The heifers were inseminated on the second to fifth day after the removal of the tampons. The average performance in the application of the tampons was 38.5 tampons per hour, and in their removal 20.7 tampons per hour. The retention rate of the tampons was 97.6%; out of this, 79.8% of the tampons were pulled out by the silon thread. The signs of heat were good, 87.9% of the heifers could be inseminated intrauterinally. All the heifers with retained tampons were inseminated. The conception rate after the first insemination was 32.7%, after the second insemination 56.4%, and after two inseminations 68.1%. Out of the synchronized heifers, 8.1% were culled for slaughter. The drawbacks of this treatment include the low conception rate of the synchronized heifers, a high requirement for repeated insemination in the synchronized oestrus, and, consequently, a high sperm consumption.


[Electrophoretic examination of changes in the protein spectrum of dogs after exposure to beta, beta'-dichlorodiethylsulfide]. In serum proteins, the alpha 3 + 4-globulin subfraction increases with a corresponding decrease of albumins. A statistically significant rise was observed from the 24th-48th hour from application with a progressive tendency reaching its maximum in the terminal stage of intoxication. This elevation reaches the values of 100% of the initial control values in the terminal stage. The drop in albumins is less significant and almost reciprocal with the rise of alpha-globulin content. In the values of beta-globulins, a change was observed in the quotient of beta 1/beta 2 globulins. No changes were ascertained in the values of gamma-globulins. Our results correspond to the data published by Gjessing and Chanutin, who observed a drop in albumins and rise in alpha-globulins after percutaneous implantation of the substance. The results suggest that the latent time between implantation and a statistically significant rise of the alpha-globulin fraction in the serum is 24-48 hours.


Animals as monitors of environmental quality. The various species of domesticated and wild animals can be excellent monitors of environmental quality. Although analyses of industrial air and water effluents and tests for toxicants in soils, plants, foods and feeds may provide some degree of predictability of environmental quality, the ultimate monitors are those organisms having metabolic activities that are comparable to man. If we closely observe animals that share our environment, like the coal miner's canary, they will alert us to unseen and perhaps devastating environmental hazards.


Transfusion of hydroxyethylated amylopectin-protected frozen blood in man. I. Plasma clearance and renal excretion of the cryoprotectant. In man following the autologous transfusion of blood previously frozen with 14% low molecular weight-hydroxyethylated amylopectin (cryo-HES), the clearance of this material from the intravascular space was compound, and appeared to consist of exponential components. The overall half-life -- however, was 10.6 +/- 3.0 (SD) h. Approximately 17% of the total infused cryo-HES was excreted in the urine 1 h postinjection, and 40% by 72 h. The erythrocyte sedimentation rate (ESR) was not affected by the presence of this substance in the bloodstream of the recipient. The results indicate that cryo-HES is removed rapidly following the transfusion of blood previously frozen with this material.


IgG levels in mother-father-cord trios. Evidence for a large reduction of maternal IgG at birth. Cord plasmas have a higher concentration of IgG than do the mothers, although autologous, fetal immunoglobulin G is only a small fraction of the neonate's complement. Maternal IgG levels are significantly lower than the nonpregnant adult female, a loss of about one third, which cannot be explained completely by maternal immunization of the fetus.


Detection of the H and I blood group antigens in normal plasma. A comparison with A and i antigens. The levels of A, H, I and i antigens were measured in the plasma of 185 normal subjects by the agglutination-inhibition method. The presence of H in the plasma was only detectable with immune anti-H. The level of H in the plasma was directly correlated with the amount on the red cells, and was affected by the donor secretor status. The plasma of group O secretors contained more H than the plasma of donors of other phenotypes. On the other hand, I and i plasma antigens were not related to the other systems studied. Unlike the Ii antigens on the red cell membrane, there was no relationship between the levels of I and i in plasma.


[Kinin system components, free kinins and proteinase inhibitors in the edematous fluids of nephrotic syndrome patients]. Main components of the kinin system, free kinins, total arginine esterase activity content of alpha 1-antitrypsin and alpha 2-macroglobulin fractions were estimated in various edematous fluids (transduates of different localization, pleural exudates of the inflammatory type) of patients with nephrotic syndrome of various etiology. Noninflammatory edematous fluids (interstitial, abdominal and pleural transudates) were found to contain activated kallikrein and prekallikrein from blood plasma; 3-10 ng/ml of free kinins were present in interstitial edematous fluids and 30-60 ng/ml - in abdominal transudate. Kinins of abdominal transudate were identified with bradikinin by chromatographic properties; a single low-molecular form of kininogene was found, its content did not exceed 10% of the substance occurring in blood plasma of the patients. These edematous fluids practically did not exhibit the kininase activity and contained unsignificant amounts of proteinase inhibitors. Pleural exdates of the inflammatory type were distinctly different from transudates in content of the kinin system components. Depending on the higher content of protein (2.5% as compared with 0.3-0.7% in transudates) the exudates contained high-molecular kininogene and kininase I. Relative content of kallikrein in pleural exudates was lower and that of prekallikrein - higher as compared with transudates; acid kininogenases were not observed. Free kinins (30 ng/ml) were found in three samples of pleural exudates out of five samples studied. The inflammatory type of pleural exudates correlated with the high level of alpha 1-antitrypsin. As shown by comparative analysis of protein fractions from edematous fluids and corresponding samples of blood plasma of patients with nephrotic syndrome, diffusion is the main reason, which determines the course of protein transition from inter-into exovasal space, under conditions of increased vascular permeability. Kallikrein activation and extravasal formation of bradikinin were apparently the long-term affecting factors, supporting the state of increased vascular permeability in nephrotic syndrome; they had an aggravating role in pathogenesis of refractory nephrotic edema, nephrotic crises and cutaneous erythema.


A new case of gamma heavy chain disease: clinical, immunochemical and structural characterization. A new case of gamma heavy chain disease (gamma HCD) is described in a 77-year-old woman. The serum and urine contain an M-component and electrophoretic, antigenic and ultracentrifugal properties resembling those of the Fc fragment of IgG globulin. Analysis on SDS-polyacrylamide gel electrophoresis and ultracentrifugal studies show that gamma HCD portein is present in the serum as a dimer with a molecular weight of 58,000 daltons. Analysis of isotypic and allotypic markers along with the structural studies show that this HCD protein belongs to the IgG subclass and that deletion includes the total VH and CH1 regions with sequence starting at residue 225 in the middle of the hinge region.


A new antigenic determinant on HBsAg. Geographic and subtype distribution and association with HBeAg and anti-HBe. A new antigenic specificity for HBsAg is described, and its usefulness as an epidemiological marker is discussed. This specificity, l, was found in specimens from all geographic areas studied (United States, Latin America, South Africa, the Solomon Islands, and New Guinea). In these areas, l was strongly associated with HBsAg/ay; y-positive, l-negative samples were observed only among specimens from United States volunteer blood donors. This determinant allowed a distinction of HBsAg/ad classes. Thus, the l determinant was detected in 51.4% of HBsAg/adw4, 44.1% of HBsAg/adw(non-w4), and 50% of HBsAg/adr. The association of l and other HBsAg determinants with HBeAg or anti-HBe was also investigated. HBeAg was found to be associated with the presence of the l determinant and with the r determinant. Anti-HBe was associated with the presence of the d and w determinants and with the absence of the l specificity.


Human IgE response to the administration of blood components. II. Repeated gammaglobulin injections. 43 adults from a renal dialysis unit staff have received regularly spaced gamma-globulin administrations for hepatitis B prophylaxis. Several blood samples were collected over a prolonged period of time (160 days). Following gamma-globulin administration, anti-immunoglobulin antibodies of the IgE class were detected in 80% of this population, a fortnight after the first injection using serum absorptions on polymerized gamma-globulins or a specific inverse RAST method. The reactivity pattern of these IgE anti-immunoglobulin antibodies was similar to that observed for the anti-immunoglobulin antibodies with "limited specificity" detected by passive hemagglutination, in that they reacted with only one of the immunoglobulins of the panel used for their detection. A decrease of the overall IgE levels was observed in 62% of the subjects for a prolonged period of time following gamma-globulin administration. This suggests a feedback regulation mechanism for the reagin production in man, as it has already been observed in animals. A high incidence of anti-immunoglobulin antibodies of various classes was observed in this study. However, only a small number (4/43) of adverse reactions appeared following gamma-globulin administration. For some of these subjects, the presence of specific IgE anti-immunoglobulin, detected by the inverse-RAST technique, suggests a possible role of such antibodies in some intolerance reactions to gamma-globulin administration.


Chido, Rodgers and C4. In vivo and in vitro coating of red blood cells, grouping and antibody detection. C4 sucrose/low ionic strength (LIS)-coated red blood cells (RBC) are excellent for the detection of the previously 'nebulous' antibodies, anti-Chido and anti-Rodgers, as well as for serum/plasma typing of these antigens by an inhibition technique. By enzyme treatment of such cells, it is confirmed that the Ch and Rg antigens reside on the C4d part of the C4 molecule. Freshly taken RBC from normal individuals were examined with a sensitive Auto-Analyzer technique with anti-Chido, anti-C4 and anti-C3 sera. All normal RBC were shown to have C4d and C3d components on their surface. The technique was also very sensitive for the detection of the Ch antigen, which was detected on the RBC of all Chido-positive individuals, and which did not show great variation in strength by this method. The mode of in vivo C4 fixation on normal RBC seems to be different from the fixation in LIS or by RBC antibody-mediated activation.