Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes. Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.


In vivo effects of anti-Ia alloantisera. I. Elimination of specific suppression by in vivo administration of antisera specific for I-J controlled determinants. The in vivo effects of intravenous administration of alloantisera directed to I-J subregion coded determinants were investigated. In confirmation and extension of our previous results, anti-I-Jk [B10.A(3R) anti-B10.A(5R)] and anti-I-Js ([B10.A(3R) X B10.S(9R)]F1 anti-B10.HTT) antisera, when administered in 1 to 10 microliter amounts at the time of immunization, led to twofold increases in the IgM and IgG plaque-forming cells (PFC) responses to suboptimal doses of sheep erythrocytes in A/J (I-Jk) and SJL (I-Js) mice, respectively. To assess whether this immunopotentiation was due to a decrease in specific suppression, experiments were carried out using the polypeptide antigens random linear terpolymer of L-glutamic acid60, L-alanine30, and L-tyrosine10 (GAT) and random linear copolymer of L-glutamic acid50-L-tyrosine50 (GT), since administration of GAT to the nonresponder strain SJL, or GT to the nonresponder strain CBA fails to induce a primary PFC response and stimulates specific suppressor T cells able to prevent PFC responses to subsequent challenge with the immunogens GAT-methylated bovine serum albumin (MBSA) or GT-MBSA, respectively. The current study demonstrates that CBA (I-Jk) mice given 100 microgram GT in Maalox-pertussis adjuvant on day 0, and 10 microliter anti-I-Jk antiserum i.v. on days 0, 1, and 2, develop a significant primary specific PFC response on day 7. A similar responsiveness to 10 microgram GAT is found in SJL mice treated with 10 microliter anti-I-Js antiserum for 3 days. This same active anti-I-Js antiserum does not permit CBA mice to respond to GT, demonstrating the specificity of the anti-I-J effect. These data suggest that anti-I-J antiserum treatment at the time of antigen administration reduces suppressor responses to GAT or GT, permitting primary PFC responses. To directly demonstrate such an effect on suppressor activity, SJL or CBA mice treated, respectively, with GAT or GT to induce suppressor cells active on GAT-MBSA or GT-MBSA responses after adoptive transfer to normal syngeneic recipients were also given anti-I-J antisera (10 microliter/day) for 3 days, at which time their spleen cells were tested for suppressive activity upon transfer. Cells from such treated mice failed to show detectable suppressive activity upon transfer to syngeneic recipients challenged with GAT-MBSA or GT-MBSA, confirming the hypothesis of an in vivo effect of anti-I-J antiserum on suppressor activity.


Cellular and genetic restrictions in the immunoregulatory activity of alpha-fetoprotein. I. Selective inhibition of anti-Ia-associated proliferative reactions. Alpha-fetoprotein (AFP), a major alpha-globulin component of fetal and newborn sera, has earlier been shown to exert significant immunosuppressive activity in vitro on T-dependent-immune responses. In the present investigation we have examined the effects of AFP on the recognition and proliferation of T lymphocytes responding in mixed leukocyte culture against histocompatibility-associated alloantigens. Fetal-derived AFP could be shown to exert differential effects on both primary and secondary responses ranging from strong inhibition to occasional enhancement, depending on the stimulating antigens. Proliferative responses against major histocompatibility complex (MHC) I region determinants, mediated predominantly by Ly 1 + cells, were markedly suppressed. Suppression was also observed in responses against Mls locus products, an antigenic system whose recognition requires concomitant recognition of I region gene products on the stimulating cells. In contrast, responses against MHC K or D region determinants, mediated predominantly by Ly 2 + cells, were generally unaffected by AFP. Similarly, non-MHC loci alloantigens distinct from Mls locus products also induced T-cell proliferation which was refractive to suppression by AFP. Because neither Ly 1 + nor Ly 2 + cells responding in this latter situation could be inhibited by AFP, we concluded that the mere fact that a T cell expresses a particular Ly phenotype does not predetermine sensitivity to AFP-induced suppression. In any case, AFP exerts a highly selective suppressive activity on I region-associated immune responses. These data may help to resolve the present controversy over the possibility that AFP has an in vivo relevance as an immunosuppressive agent by pointing out the importance of selecting proper genetic situations for study.


Immunologic responsiveness of the C3H/HeJ mouse: differential ability of butanol-extracted lipopolysaccharide (LPS) to evoke LPS-mediated effects. The lipopolysaccharide (LPS)-protein complex extracted from the cell wall of Escherichia coli K235 by the butanol-water technique has been shown to evoke a mitogenic response in bone marrow-derived (B) lymphocytes from the C3H/HeJ mouse strain. These mice are resistant to the effects of LPS extracted with phenol. Therefore, the ability of butanol-extracted LPS to modulate a spectrum of C3H/HeJ B-cell functions was investigated. Both butanol-extracted (LPS-B) and phenol-extracted (LPS-P) LPS preparations activated responder C3H/St spleen cell cultures to polyclonal antibody production, while only LPS-B activated C3H/HeJ spleen cells. Both LPS-P and LPS-B acted as adjuvants when injected after aggregated human gamma globulin (HGG) in C3H/St mice, but neither preparation was effective as a adjuvant in C3H/HeJ mice. LPS-P injected with deaggregated HGG (tolerogen) into LPS-sensitive mice has been shown previously to inhibit the induction of tolerance HGG. In the present studies, it was shown that LPS-B, but not LPs-p, was able to inhibit tolerance induction to HGG in the C3H/HeJ, whereas both preparations were effective in the C3H/St. LPS has also been shown to bypass tolerant T cells in LPS-sensitive mice late in tolerance to HGG at a time when B cells are responsive. However, in the C3H/HeJ, neither LPS-B nor LPS-P was capable of this function. The responsiveness of these B cells to HGG was demonstrated in transfer experiments. Thus, in the C3H/HeJ, LPS-B stimulates mitogenesis, polyclonal B-cell activation, and inhibition of tolerance induction, but cannot act as an effective adjuvant or as a bypass mechanism to activate B cells in the presence of tolerant  T cells. The explanation for this pattern of responses may be attributable to yet  another cellular defect in the C3H/HeJ mouse.


Immunochemical studies on blood groups LXVI. Competitive binding assays of A1 and A2 blood group substances with insolubilized anti-A serum and insolubilized A agglutinin from Dolichos biflorus. Competitive binding assays using 3H-labeled blood group A substance and insolubilized Dolichos biflorus lectin or human anti-A were carried out, measuring competition by blood group A1 and A2 glycoproteins, and by unabsorbed anti-A sera, and with these sera absorbed with the A1 and A2 glycoproteins. With Dolichos lectin specific for (formula: see text) A1 substances had about 11 times as many determinants as did A2 substances, but the slopes of the lines in the competitive binding assays were the same. With insolubilized anti-A, A2 substances gave lines of lower slopes. Although individual A1 populations varied in the amounts giving 50% inhibition in the assays, as did A2 substances, the slopes of the lines for the A1 substances were the same and always higher than the slopes of the lines for the A2 substances. Competitive binding assays with unabsorbed anti-A sera and with these sera absorbed with insoluble polyleucyl A1 and A2 substances showed that partial absorption of polyleucyl A1 substances left antibodies of lower slope in the supernate, whereas absorption with polyleucyl A2 substance left antibodies (anti-A1) having the same or an even higher slope than the unabsorbed sera. The findings indicate that human A1 and A2 glycoproteins differ in their determinants, and that A2 specificity is determined by the type 2 chain in which the A trisaccharide (formula: see text) is linked beta 1 leads to 4 to DGlcNAc, whereas the A1 specificity is determined by the type 1 chain in which this trisaccharide is linked beta 1 leads to 3 to DGlcNAc; most of the determinants in the glycoproteins have a second LFuc linked alpha 1 leads to 3 and alpha 1 leads to 4 to the DGlcNAc of the type 2 and type 1 chains, respectively.


Deposition of retrovirus associated antigens (p30 and gp70) on cell membranes of feline and murine leukaemia virus infected cells. A quantitative estimation of retrovirus associated cell membrane antigens of murine and feline cells infected with their respective type C leukosis virus is presented. Using a radio-immune assay with three broadly reactive antisera, the minimum estimated number of retrovirus associated antigenic determinants on YAC [Moloney leukaemia virus (MuLV) infected murine] and FL-74 [feline leukaemia virus (FeLV) infected feline] cells was 1.3 x 10(6) and 1.6 x10(6) determinants per cell respectively. The virus structural proteins p27-30 and gp70 were detected by three component specific antisera on murine and feline cell surfaces in amounts which varied between cell isolates. MuLV infected cells produced as many as 1.9 x 10(5) p30 antigenic determinants and 7.5 x 10(5) gp70 determinants on infected cells. FeLV infected cells (FL-74) expressed 5.6 x 10(5) p27 and 7.5 x 10(5) gp70 antigenic determinants per single cell surface. The major core protein (p27-30) and the major envelope glycoprotein (gp70) antigens are sufficiently physically separated on cell surfaces so that binding of either of the membrane antigens with component specific antibodies does not interfere with binding of antibodies specific for the other. Despite the expression of interspecies determinants for p30, gp70, and other retrovirus associated antigens detected by antibody procedures, interspecies determinants of cell mediated immunity could not be demonstrated in immune mice bearing Moloney sarcoma virus (MSV) induced tumours. Furthermore, xenogeneic immunization of mice with FL-74 cells failed to protect mice against the growth of MSV induced lymphoma or sarcoma.


Antigens of hepatitis B virus: failure to detect HBeAg on the surfaces of HBsAg forms. The particulate forms of HBsAg were analysed for the presence of HBeAG on their surfaces. By immunodiffusion analysis, anti-HBe did not form precipitin bands with the purified forms of HBSAg and hyperimmune guinea pig antisera to these forms did not react with HBeAg. Lines of non-identity were observed between the HBeAg determinants (e1 and e2) and the Dane particles and filaments isolated from an HBeAg-positive serum. Finally, anti-HBe failed to precipitate the polymerase-positive subpopulation of Dane particles, indicating that anti-HBe has no direct role in virus neutralization.


Serological relatedness of monkeypox, variola, and vaccinia viruses. Closely related human and monkey orthopoxviruses were differentiated by serologic techniques. Antiviral sera were tested by immunodiffusion for reactivity against six different viral antigens prepared from either infected cell cultures or infected chorioallantoic membranes (CAMs) of embryonated eggs. Portions of each antiserum were separately absorbed with heterologous antigens from infected CAMs to remove common reactivity. The absorbed sera formed immunodiffusion precipitates with both types of antigen preparation and revealed specific-character differences that made it possible to classify the viruses as variola, vaccinia, or monkeypox. Cross-complement fixation tests were also used to examine the immunologic reactivities of antisera to detergent-treated, purified preparations of three orthopoxviruses. Only common reactivities were detected by this method, however, and differentiating reactivities were not observed.


Epilepsy in children. An etiological study based on their obstetrical records. Events which might have a casual significance for epilepsy were collected from the obstetrical case reports of 100 epileptic children who were born in four hospitals in a large town. 100 healthy children of the same age, who had been born in the same hospitals, served as a control group. The differences were worked out by means of the Chi square test and where small numbers were involved the Yates theory was used. It indicated that some possibilities of damage (e.g. higher age of the mother at birth, toxemia of pregnancy, premature birth, heavy weight at birth) are important either with respect to all patients or to the different types of attacks, whereas other factors (e.g. abnormal positions, instrumental delivery, coiling of the umbilical cord) whose roles are likewise never usually doubted, can be neglected. Exogenous reactions were found most frequently in the case of patients with grand mal and focal attacks, although, as was expected, they were missing in patients with absences, whose main genetic nature is known. It is pointed out that only with extreme caution may the various possibilities of damage be found responsible for epilepsy in children in general or for the individual types of attacks.


Botulism: clinical neurophysical findings. Four cases of mild botulinus type B intoxication are reported with the clinical neurophysiological studies. Electromyographically tetanic stimulation of the N. ulnaris initially led to tetanic potentiation of the muscle action potential. After an interval without any symptoms tetanic reduction became apparent between the fourth and seventh week of the illness. The electroneurographic finding was normal during the observation period of three months. Infrared reflex pupillographic studies revealed that the cholinergic autonomous synapses were disturbed for a period much longer than the symptoms clinically established. The speed at which the pupillographic findings returned to normal varied considerably according to the patient. Electroencephalographic results indicated generalized groups of slow high amplitude waves in three of the four cases during the period of observation. The pathophysiology of botulinus intoxication is discussed with a consideration of the literature and the results of this study.


The effect of large doses of dexamethasone on the cerebrospinal fluid pressure in patients with supratentorial tumors. The effect of large doses of dexamethasone (80 mg) on the cerebrospinal fluid pressure (CSFP) was investigated with continuous lumbar CSFP measurement over 24 h in 10 patients with supratentorial cerebral tumors and clinical signs of elevated intracranial pressure. There was a further slight rise in CSFP with an unchanged pressure pattern in the course of observation of the untreated control group. A marked lowering of CSFP was observed within 6 h after initial intravenous administration of dexamethasone to seven of the treated patients. In four of the treated patients an unequivocal and in five only a moderate CSFP lowering was measured at the end of the registration. One patient had a slight rise in pressure. The plateau waves of all the patients treated decreased in height, frequency and duration within the first hours, while fluctuations in pressure level and CSFP amplitude were reduced.


Adult-onset of Tangier disease: 1. Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration. A 67-year-old woman, with the typical biochemical features of Tangier disease, had a syringomyelia-like syndrome which has now been observed in several patients with symptomatic onset in adult life. She developed progressive facial diplegia, bilateral wasting of hand muscles and loss of sensation over cranial, cervical and brachial dermatomes over 17 years. Nociception alone was first affected, then nociception and thermal discrimination and finally all modalities of sensation. Quantified tests of cutaneous sensation confirmed that sensation was normal in lower limbs but markedly abnormal in upper limbs. Biopsied fascicles of cutaneous nerves from clinically affected (forearm) and from clinically unaffected (leg) regions permitted a comparison of well-advanced and early pathologic lesions, respectively. The selective vulnerability of unmyelinated and small myelinated fibers in affected regions in this disorder has been confirmed. The earliest morphologic abnormalities of myelinated fibers, but seen infrequently, were mitochondrial enlargement and structural abnormality, aggregation of mitochondria and dense bodies and clusters of neurofilaments. Increased numbers of sudanophilic lipid droplets did not seem to form in Schwann cell cytoplasm prior to fiber degeneration. On the contrary, for myelinated fibers there appeared to be an altered process of axonal degeneration from that seen in Wallerian degeneration and in other axonal degenerations. Distinctive linear bands of closely-packed, minute, osmiophilic and clear lipid droplets formed and their further degradation appeared delayed. Although less clearly demonstrated, lipid droplets in Schwann cells of unmyelinated fibers also appeared to form following their degeneration. We would propose that in Tangier disease, the degradation of myelin ovoids to neutral lipid in Schwann cells does not appear to be delayed. However, further degradation of neutral lipid or its transport away from Schwann cells appears to be retarded.


Erythrocyte ghost (Na+ + K+) ATPase activity in mice with hereditary muscular dystrophy (strain C57 BL/64J/dy). Erythrocyte ghost (Na+ + K+) ATPase activity was studied in mice with hereditary muscular dystrophy (strain C 57 BL 6J/dy) and appropriate controls. No difference was observed in the enzymatic activity between dystrophic and any of the healthy genotypes. Ouabain 5 mM and 0.1 mM inhibited the enzymatic activity and no difference was observed between dystrophic and control animals. The results are discussed in the light of the literature.


Immunoglobulin M specific for measles in serum and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Serum and cerebrospinal fluid of patients with multiple sclerosis, subacute sclerosing panencephalitis and other neurological disease have been tested by the indirect fluorescent antibody method for immunoglobulin M specific for measles. Only sera of three patients were positive. This feature is of little statistical importance. Nevertheless the authors emphasize the role of a possible viral infection in the pathogenesis of multiple sclerosis.


Interactive effects of age and cerebral disease on cognitive performances. A battery of mental tests was given to groups of younger (16--44 years) and older (48--60 years) control and cerebral diseased patients. Each patient in the younger cerebral diseased group was matched individually with an older cerebral diseased patient for type and site of lesion. Each patient with cerebral disease was matched individually with a control patient for age, educational level and sex. Differences in level of test performance related to age were generally greater for cerebral diseased than for control patients. Differences in level of test performance related to diagnostic category were generally greater for older than for younger patients. Analysis disclosed a significant overall interactive effect of age and cerebral disease on the performance of mental tests, supporting the hypothesis that acquired cerebral disease has more severe behavioral consequences in older than in younger persons.


Further investigations on benign myopathy with autosomal dominant inheritance. Six members of a family suffered from benign myopathy over four generations. The clinical, laboratory, electromyographic, histological and genetic data were consistent with benign myopathy with autosomal dominant inheritance. Congenital torticollis was a feature in one patient. Linkage studies revealed no linkage between the locus of this myopathy and the locus of any of 17 genetic markers investigated. This family was of Polish descent, which indicates a widespread occurrence of this benign hereditary myopathy. The data presented are a strong argument in favor of a specific new disease entity.


Immunoglobulin abnormalities in relatives of IgA deficient epileptics. Serum levels of IgA were found to be reduced in some patients with epilepsy. Further studies revealed that only epileptics with constitutional factors for seizures showed, if ever, IgA deficiency, particularly those treated with hydantoins (up to 25%). In order further to substantiate the association of immunoglobulin alterations with epilepsy nine families in whom the disease was clustered were investigated. An IgA deficiency was detected in 16 of the 19 epileptics (three without hydantoin medication), but in none of their 45 non-epileptic relatives. However, four of the relatives had a low IgM. Seven other families were tested in each of which only one IgA deficient epileptic was known. No other family members were found with a low IgA, but 24 of 58 such relatives had increased IgM serum concentrations. The association of IgA deficiency and epilepsy with IgM imbalances in relatives of IgA deficient epileptics gives additional support for the hypothesis that immune imbalances and certain forms of epilepsy might be linked.


Simultaneous recording of pupillary hippus and EEG. Report of a case. Pupillary hippus was observed and recorded in a man of 44 years, who had epileptic seizures, chronic alcoholism with liver disease and Primidon intoxication, during a period of unconsciousness of 24 h. During this time the simultaneous records of the EEG and pupillogram over a long period of time revealed that the basic EEG rhythm and hippus had the same frequency. Both recordings were temporarily in phase, time-locked, and could be blocked by painful and acoustic stimuli. The etiology and interpretation of hippus are discussed.


Meningoencephalitis syndrome following influenza vaccination. Immunological reactions to non-virus substances of vaccines may be of considerable significance to the pathogenesis of neurological complications after anti-influenza vaccination. A 60 year old female patient with a known allergic diathesis developed a meningoencephalitis syndrome a few hours after vaccination. The case history as well as the clinical course suggested an immunopathogenetic mechanism. We therefore analyzed the immune profile. Intracutaneous testing with chicken meat and chicken egg protein lead to a striking local anaphylactic reaction which is discussed in causal relation to the postvaccination complication.


[Broca's aphasia. The clinical picture and a consideration of the neurolinguistic structure (author's transl)]. Broca's aphasia is characterized by disorders on the phonemic, syntactic and lexical level of linguistic description. It is not only the patient's speech which is impaired; abilities to comprehend, read and write are likewise impaired. Articulatory disorders (dysarthria) which are due to an impaired innervation of the phonatory and articulatory musculature may exist. However these disorders do not account for all the linguistic deficits found in cases of Broca's aphasia. The characteristic feature enabling a differential diagnosis of Broca's aphasia is agrammatism.


Diagnostic value of saccadic pursuit eye movement in screening for organic cerebral dysfunction. In order to validate the results obtained in a preliminary investigation the saccadation of slow pursuit eye movements was examined in 19 patients with unilateral brain damage, in 25 patients with diffuse cerebral disease and in 26 neurotic patients. The diagnostic significance of saccadation was ascertained in detecting general cerebral dysfunction. By means of a discriminant function combining the parameters, "number" and "size", of saccades more than 80% of the brain-damaged patients and controls could be identified correctly, but the side of the cerebral lesion could not be determined.


Pain perception in man after long term spinal cord stimulation. Thresholds of non-painful and painful perception for electrical stimuli are not altered significantly during dorsal column stimulation either in the area of induced paresthesia or outside it. After long term stimulation of the dorsal column the thresholds for stimuli are significantly higher within the area of induced paresthesia but not outside it. Median nerve evoked somatosensory cortical potentials are not altered by conditioning or simultaneous DC stimulation. During DCS in three of eight patients only the vibration evoked cortical potentials were attenuated in the early three components of the potential.


Parkinsonism and dementia with acoustic neurinomas. Report of three cases. Three cases of acoustic neurinoma with parkinsonism and dementia are reported. The characteristics of parkinsonism seen in these cases consisted of the rapid development of symptoms and symmetrical rigidity. In all cases there was a marked enlargement of the ventricular system and transient improvement in their mental states was observed following ventriculoperitoneal shunt or removal of the tumor. In an autopsy case there were no pathological findings in the cerebral cortex, basal ganglia, substantia nigra or pontine nuclei. It was concluded that parkinsonism and dementia in these patients were caused by chronic hydrocephalus due to the acoustic neurinomas.


Lymphocyte stimulation by acetylcholine receptor in polymyositis. Lymphocytes of twenty-seven patients with polymyositis were incubated in vitro with cholinergic receptor rich membranes obtained from the electric organs of Torpedo Marmorata. Lymphocytes of polymyositic patients were slightly stimulated; positive responses were present mainly in patients affected from more than a year. Sensitization against the nicotinic cholinergic receptor may explain the occurrence of the myasthenic syndrome with polymyositis.


The sodium pump of erythrocytes from patients with Duchenne muscular dystrophy: effect of ouabain on the active sodium flux and on (Na+, K+)ATPase. Active ion exchanges across erythrocyte membrane from patients with Duchenne muscular dystrophy were studied by two methods: --erythrocyte ghosts (Na+,K+)ATPase activity and its sensibility to ouabain, using an enzymatic method; --active sodium outflux and its sensibility to ouabain using a radioisotopic method. (Na+,K+)ATPase activity and active sodium outflux were decreased in dystrophic patients compared to normal sex- and age-matched controls. Enzymatic activity and active sodium outflux were inhibited by ouabain 10(-4) M in patients and in controls. Inhibition of the active sodium outflux was lower in patients than in controls. The results are discussed in light of the literature.


Alpha-fetoprotein, prealbumin, albumin, alpha-1-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors. According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.


Raised alpha-fetoprotein levels in amniotic fluid and maternal serum associated with distension of the fetal bladder caused by absence of urethra. Raised alpha-fetoprotein concentrations were found at 29 and 30 weeks' gestation in the amniotic fluid and maternal serum of a woman who presented in her seventh pregnancy with apparent polyhydramnios. The fetus had multiple abnormalities including gross distension of the bladder resulting from absence of the urethra, intestinal artresia, and a congenital heart defect.


Cryo-ultramicrotomy and myofibrillar fine structure: a review. In the past, the techniques of electron microscopy and X-ray diffraction have both been very informative about the ultrastructure of the muscle myofibril But X-ray diffraction patterns are difficult to interpret unambiguously and until now specimen preservation in plastic embedded muscle has been sufficiently poor to make it difficult to use electron micrographs of muscle as a means of interpreting the available X-ray diffraction evidence. The possibility of using ultrathin sections of frozen muscle, in which the disruptive steps of chemical dehydration and plastic embedding can be avoided, promises to help to bridge the information gap between present X-ray and electron microscope results. For this reason we here review the application of the cryosectioning technique to muscle, we assess the technique in terms of the improvements in preservation which have so far been obtained and which might be expected and we discuss some of the many potential advantages and uses of this technique for studies of muscle ultrastructure and function. It is concluded that this technique should be developed vigorously since it promises to play a very important role in muscle research in the future.


Purification and immunologic evaluation of human melnoma-associated antigens. Melanoma-associated antigens (MAA) were isolated and their functional immunologic properties were evaluated. Spent fetal calf serum-free culture media and 3-m KCI extracts of cultured human melanoma cells grown in this medium were used as antigen sources. Ultracentrifugal flotation on KBr was used to separate MAA and HLA antigens present in the extracts or spent culture media; thus interference by histocompatibility antigens was prevented in subsequent tests of tumor antigenic activity. MAA purified in this manner retained their immunologic functions as evidenced by their ability to produce delayed cutaneous hypersensitivity reactions in patients with melanoma, specifically combine with antimelanoma xenoantibody, and elicit production of functionally specific xenoantibody. Possible structural differences between HLA antigens and MAA were considered in evaluation of the data.


Immune responses in human colon cancer. II. Cytotoxic antibody detected in patients' sera. Complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and spontaneous cell-mediated cytotoxicity (SCMC) were evaluated in patients with colon cancer with the use of a 51Cr release microcytotoxicity assay. We studied the sera and peripheral blood lymphocytes (PBL) from patients with colon cancer as well as from normal controls using three separate human colon cancer cell lines as targets. Antibody active in either the CDC or ADCC assay was detected in 11 of 14 (79%) patients with colon cancer, but none was found in 18 normal individuals. The ability of PBL from patients with colon cancer and from normal controls to mediate ADCC and SCMC did not differ significantly.


Experimental horizontal transmission of feline leukemia viruses of subgroups A, B, and C. Experiments were conducted with cats in metal cages inside plastic isolators to determine whether feline leukemia virus (FeLV) of the three known antigenic subgroups (A, B, and C) is transmitted horizontally from infected cats to normal "contact" cats. Blood smears collected at weekly intervals were examined by the fixed-cell, indirect immunofluorescence test for FeLV internal p30 to follow the spread of infection from inoculated cat to contact cats. These studies established that viruses of all three subgroups are transmitted horizontally among kittens and adults with slightly varying degrees of speed. Virus was reisolated from one horizontally infected contact cat of each group, and its envelope antigenic type was the same as that originally inoculated into one cat of the same group. After the cats acquired the infection, they became chronic carriers of virus (viremic) during the observation period of 9 or 11 weeks post inoculation.


[Molecular biological aspects of oncogenesis caused by RNA tumor viruses (author's transl)]. This article concerns the molecular mechanisms by which RNA tumor viruses, commonly called as oncornaviruses, transfer their genetic information from the genomic RNA (70 s RNA) of the virions to the cellular DNA, leading to neoplastic transformations. The article describes biochemical and serological properties of reverse transcriptase, its role in the life cycle of RNA tumor viruses and broader implications to molecular biology. In this connection, the authors report their own findings on the role of reverse transcriptase in a preleukemic disease, myelofibrosis. This enzyme, discovered in their laboratory, is antigenically closely related to reverse transcriptase of certain primate RNA tumor viruses, and of human leukemic cells. The article also describes the role of reverse transcriptase inhibitors in viral oncogenesis. Of particular interest, is the partially thiolated polycytidylic acid (MPC) which has been developed by the authors, and is known to have a very high binding affinity to the viral reverse transcriptase. The implication of these basic data on the clinical effectivity of MPC in human leukemia, documented in a few cases, has been discussed.


Evaluation of a patient education program for chronic obstructive pulmonary disease. An audiovisual instructional program for patients with chronic obstructive pulmonary disease was evaluated in 65 patients with this disease and 20 patients without lung disease. We found that the program was successful in increasing the factual knowledge about chronic obstructive pulmonary disease, with the attainment of mean scores of 88 and 95% on postteaching tests. Patients with varying educational backgrounds achieved similar gains in knowledge.


Transmissible agent in non-A, non-B hepatitis. Plasma or serum from 4 patients with acute or chronic non-A, non-B post-transfusion hepatitis (P.T.H.) and from a blood-donor implicated in two cases of P.T.H. was inoculated into 5 chimpanzees. Biochemical and histological evidence of hepatitis developed in these 5 chimpanzees but not in a control animal. The mean incubation period in the chimpanzees was 13.4 weeks, compared with 7.7 weeks in the 4 patients with P.T.H. The peak alanine aminotransferase (A.L.T.) levels in the 5 chimpanzees were 265, 212, 219, 70, and 62 I.U./l. Histological changes ranged from mild to conspicuous hepatitis and generally correlated with the degree of A.L.T. elevation. There was no evidence of clinical disease and all animals went on to biochemical and histological recovery. There was no serological evidence of type A or type B hepatitis. Hepatitis was transmitted by serum derived from patients with chronic as well as acute hepatitis, strongly suggesting a chronic carrier state for the agent responsible for non-A, non-B hepatitis. Non-A, non-B hepatitis thus seems to be due to a transmissible agent which can persist and remain infectious for long periods.


Transmission of non-A, non-B hepatitis from man to chimpanzee. Non-A, non-B hepatitis was transmitted to four colony-born chimpanzees by intravenous inoculation of human sera. Two chimpanzees were inoculated with serum from a patient with a clinical and serological diagnosis of chronic non-A, non-B hepatitis whose blood appeared to transmit this disease to a nurse following accidental needle-stick, and the other two chimpanzees were inoculated with serum from either of two former blood-donors whose HBsAg-negative blood appeared to transmit clinically recognisable hepatitis, and who were found to have raised serum-aminotransferase levels 1 1/2 and 5 years later. Serum-aminotransferase levels rose in all four chimpanzees, beginning 2--4 weeks after inoculation: peak alanine-aminotransferase values were 210 to 328 I.U./l. Evidence of hepatitis was present in liver biopsy specimens from all four chimpanzees, beginning 8--10 weeks after inoculation. None showed serological evidence of infection with hepatitis A virus, hepatitis B virus, cytomegalovirus, or Epstein-Barr virus.


Low erythrocyte pyridoxal-kinase activity in Blacks: Its possible relation to falciparum malaria. The red-cell glucose-6-phosphate dehydrogenase (G.-6-P.D.) activity and red-cell pyridoxal-kinase (P.L.K.) activity of 27 Nigerian children with severe Plasmodium falciparum parasitaemia were compared with those of 26 healthy Nigerian children and 6 White adults. The mean P.L.K. activity of the malaria patients was similar to that of the Whites but significantly higher than that of the Nigerian controls. Correction for reduced mean red-cell age in patients was made by comparing the P.L.K.: G.-6-P.D. ratio for those subjects with stable G.-6-P.D. phenotypes. The mean P.L.K.:G.-6-P.D. ratio was the same for malaria patients and adult White but significantly higher than that for the Nigerian controls. These results suggest that the relatively high frequency of low red-cell P.L.K. activity among Blacks may have been selected for by falciparum malaria.


Diagnosis and management of testes in the superficial inguinal pouch. A physical sign was assessed and operation findings were noted in boys with testes which tended to deviate lateral to the external ring who were seen over a five-year period. Tensing the abdominal muscles by straight-leg raising not only facilitated palpation of such testes but also helped to domonstrate lateral deviation. The view that testes found lateral to the external ring and which could be pushed some way into the scrotum were merely retractile was questioned. Such testes were deviated by inguinal tethering. The spermatic cord was short enough in over half the tethered testes to require retroperitoneal dissection to achieve the fully descended position, not a significantly different proportion compared with the obstructed group.


Aryl-hydrocarbon-hydroxylase inducibility in patients with cancer. Aryl-hydrocarbon-hydroxylase (A.H.H.) inducibility has been studied in the peripheral-blood lymphocytes of patients with squamous-cell lung cancer, of patients with cancer at other sites, and of controls matched for age, sex, social class, and smoking habits. The proportion of high inducers was significantly greater among patients with lung cancer (but not patients with other cancers) than among controls, which suggests that, besides smoking, a constitutional factor may be involved in the pathogenesis of lung cancer.


Sclerodermatous graft-versus-host disease limited to an area of measles exanthem. A female patient with severe idiopathic aplastic anaemia received a successful bone-marrow transplant from her HLA-identical, mixed-lymphocyte-culture-compatible, brother. 8 months after transplantation she had localised cutaneous measles. Chronic sclerodermatous changes developed which were indistinguishable from chronic graft-versus-host disease and were limited to the areas of the original exanthem. Interaction between viral infection and minor histocompatibility differences probably resulted in graft-versus-host disease in this patient.


Immunoradiometric assay of procoagulant factor-VIII antigen in plasma and serum and its reduction in haemophilia. Preliminary studies on adult and fetal blood. An immunoradiometric assay (I.R.M.A.) for antihaemophilic factor (factor VIII) has been developed which is based on a human inhibitor to procoagulant factor VIII (FVIIIC) which arose in a polytransfused haemophiliac. The assay detected and measured the antigen related to FVIIIC (FVIIICAg) in normal plasma and serum but failed to detect any antigen in samples from five patients with severe haemophilia. In a sixth patient with severe haemophilia a non-parallel dose-response curve was obtained. FVIIICAg was also present in plasma and serum from six samples of cord blood and in two samples of fetal serum obtained after termination of pregnancy. The assay may, therefore, be used to measure FVIIICAg in small serum samples and provides a potential practical method for prenatal diagnosis of haemophilia.


Does normoxic pulmonary vasodilatation rather than hypoxic vasoconstriction account for the pulmonary pressor response to hypoxia? A mediator of the pulmonary pressor response to hypoxia has not been found. The pressor phenomenon could be explained if the pulmonary vasodilatation present during normoxia were maintained by a vasodilator substance such as bradykinin. Ventilation of the lungs with air or oxygen causes the release of bradykinin which is rapidly inactivated in the lungs. Inhibition of the inactivating enzyme prevents the development of pulmonary hypertension in response to chronic hypoxia. Bradykinin is formed in the blood and is also present in alveolar macrophages, which arise from precursors in haematopoietic tissue. Formation of bradykinin by granulocytes is critically dependent on the local oxygen tension. The enzyme which inactivates bradykinin also converts angiotensin I to angiotensin II and thus provides a mechanism for interaction between the pulmonary and systemic vasculatures. The rate of inactivation of bradykinin may be altered by small changes in pH. It is postulated that when bradykinin production is reduced during hypoxia the higher tone of the pulmonary vascular smooth muscle, maintained by numerous constrictor stimuli, asserts itself.


The hygiene standard for chrysotile asbestos. Previous studies, including the analysis on which the current 2 fibres/cm3 hygiene standard is based, may have underestimated the risk of morbidity or mortality following exposure to low levels of asbestos dust. Accurate dose-response data at levels below 2 fibres/cm3 are unlikely to be available for the foreseeable future, and the biologically plausible assumption that excess cancer mortality is approximately proportional to dust level should be provisionally accepted. It may be reasonable, however, to postulate a safe threshold for mortality from asbestosis. If excess mortality from asbestos-related disease is proportional to dust level for each cause, approximately 10% of male asbestos workers might, under certain assumptions, eventually die of asbestos-induced disease after 50 years' exposure at 2 fibres/cm3. Peritoneal mesothelioma is usually due to crocidolite (blue asbestos) or other amphiboles, but exposure to chrysotile (white asbestos) alone may lead to a substantial risk of pleural mesothelioma. These predictions are based on rather small numbers in a single factory, and further studies in other working environments are required. Fibre counts based on optical microscopy are likely to be less relevant than total counts by electron microscopy, and excess mortality is virtually confined to men first exposed more than 20 years ago, when little or no accurate data on dust levels were collected.


Critical evaluation of adenoidectomy.

Critical evaluation of adenoidectomy. In two matched groups of thirty-two children, one which had tonsillectomy alone and the other which had tonsillectomy plus adenoidectomy, the symptoms generally attributed to adenoidal hypertrophy were equally common in both groups before operation and improved with equal frequency after operation whether or not the adenoids were removed.


Localisation of insulinomas.

Localisation of insulinomas. Small insulinomas may be undetectable by arteriography or palpation of the pancreas. They can be identified, however, by the point at which high insulin levels are detected in the venous effluent sampled at several sites by catheterisation of the splenic and portal veins at laparotomy or via the percutaneous transhepatic route. Diagnosis by catheterisation techniques made it possible to resect only that part of the pancreas containing the tumour (in one patient the head and in another the body of the pancreas). Improved localisation is essential in planning an operation, and often removes the need for lengthy trials of medical therapy before laparotomy.


Maternal hyperthermia as a possible cause of anencephaly. Mothers of anencephalic infants were asked about febrile illness and sauna bathing during their pregnancies. In 7 of 63 affected pregnancies (11%), a history of maternal hyperthermia near the presumed time of anterior neural-groove closure was given. 5 had fever with a maximum recorded temperature ranging from 38.9 to 40.0 degrees C, each case being secondary to a different type of illness. The other 2 had possible hyperthermia episodes as a consequence of sauna bathing, with no infectious agent involved. The frequencies of hyperthermia at the same period of gestation in two control groups were 0% and 0.1%. This excess frequency of maternal hyperthermia at the period of anterior neural-groove closure, and the differing natures of its causes, imply that hyperthermia itself may be an aetiological factor in anencephaly.


Pathogenesis of gastric cancer in pernicious anaemia. A pathogenetic mechanism to explain the increased incidence of gastric cancer in patients with pernicious anaemia (P.A.) is proposed. Mean nitrite concentration in gastric juice from thirteen fasting patients with P.A. was nearly fiftyfold greater than that of age-matched controls. The number of bacteria in the gastric juice of P.A. patients was also greatly increased. Small amounts of volatile nitrosamines were detected in simulated P.A. gastric juice in vitro, after addition of nitrite to achieve a concentration approximating to that found in vivo. If similar nitrosation occurs in vivo, the intragastric production of carcinogenic N-nitroso compounds could explain the high incidence of gastric cancer in patients with P.A.


Air pollution and cytological changes in sputum. The increase in sputum cellularity due to inflammatory and bronchial epithelial cells was compared in two groups of 308 and 399 subjects drawn from populations exposed to air-pollution levels common in industrialised countries. Single morning sputum specimens were examined and the differences in increased sputum cellularity between the two groups, stratified by age, sex, and tobacco consumption was assessed by the summary X2 test of Mantel-Haenszel. The group exposed to heavier air pollution had more increases in alveolar phagocytes, neutrophils, and lymphocytes, but not in eosinophils and bronchial epithelial cells. Subjects were also asked to answer a questionnaire on the symptoms of chronic bronchitis; the study showed that the inflammatory response preceded the appearance of symptoms.


Pulsus paradoxus in asthma.

Pulsus paradoxus in asthma. Ninety-three patients with asthma were examined on 308 occasions for systolic fluctuation of blood-pressure during quiet breathing. Pulsus paradoxus (fluctuation of 10 mm Hg or greater) was present on 110 occasions. A pulses paradoxus was associated with greater airflow obstruction (average peak expiratory flow-rate 33.6% of the predicted) than an absent pulsus paradoxus which was associated with a peak expiratory flow-rate of 55.4%. However, pulsus paradoxus was often present in mild obstruction and absent in severe obstruction. In six patients the effect of changing respiratory pattern on systolic fluctuation was studied. Systolic fluctuation was directly related to the inspiratory flow-rate. This is probably one of the major reasons why association of airflow obstruction with pulsus paradoxus is not constant.


Prenatal diagnosis of homozygous familial hypercholesterolaemia. Expression of a genetic receptor disease in utero. Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolaemia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125I-L.D.L. Functional consequences of L.D.L. binding to the receptor--i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification--were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses. On the basis of these findings, homozygous F.H. was diagnosed and the pregnancy was terminated at the 20th week. The diagnosis of homozygous F.H. was confirmed by a serum-cholesterol of the aborted fetus of 279 mg/dl, a value 9 times the mean of four control fetuses of similar gestational age. More than 80% of the serum-cholesterol of the affected fetus was contained within L.D.L. Prenatal diagnosis of homozygous F.H. now seems practical; moreover, the finding of a raised serum-L.D.L. in the affected fetus indicates that the L.D.L. receptor is normally functional as early as the 20th week of fetal life.


Serum-alpha-hydroxybutyrate dehydrogenase levels in sickle-cell disease and sickle-cell crisis. In patients with sickle-cell disease (Hb S/S disease) who are not in crisis, the serum-level of alpha-hydroxybutyrate dehydrogenase (alpha-H.B.D.) is significantly above normal. The degree of elevation correlates with the severity of the disease. During infarctive crises the level increases still further by a factor of 2 to 3, and it returns to the patient's normal level on recovery. The level of alpha-H.B.D. thus provides an index of the severity of the disease. Also, it allows distinction between true infarctive crisis, infection, and fake symptoms. In 5 patients a rise in the level of alpha-H.B.D. above the patient's normal level was detected several days before the onset of symptoms, which suggests that there may be a "prodromal" phase.


Cholestasis: Pump failure, microvilli defect, or both? Cholestasis may result either from a disturbance of the systems responsible for solute transport into the bile canaliculi (for example, the Na+ and K+-ATP-ase system) or from an alteration of canalicular microvilli (for example, that resulting from microfilament dysfunction). Evidence that both mechanisms operate is drawn from the analysis of experimental cholestasis induced by oestrogen, cytochalasin-B, and phalloidin.


Motivation for vasectomy.

Motivation for vasectomy. Men under 35 tend to request vasectomy for different reasons from those given by older men. Potential sexual, marital, or ageing problems seemed to motivate older couples, and problems related to family size, recent pregnancy, and difficulty with contraception the younger ones.


Reduction in incidence of rheumatoid arthritis associated with oral contraceptives. Royal College of General Practitioners' Oral Contraception Study. Analyses of the frequency of reporting of rheumatoid arthritis have been undertaken as part of the continuing major prospective survey of oral contraceptives. The rate of reporting in oral-contraceptive users (takers) is half of the rate in non-users (controls). The rates for ex-takers and controls are not materially different. The expected rise in the rate of reporting in women over 35 is apparent in controls but suppressed in takers. In the absence of any accountable bias, it is concluded that oral contraceptives protect against the development of rheumatoid arthritis. Although the effect is small, the observation may be valuable in understanding the aetiology of the disease and the mechanism of action of oral contraceptives.


Lymphocytotoxic antibodies in family members of patients with multiple sclerosis. Cold-reactive lymphocytotoxic antibodies were found in sera from 14 of 21 (67%) patients with multiple sclerosis. A significantly (p less than 0.01) greater frequency of these antibodies was also demonstrated in patients' household members (12 of 18 [67%]) compared to siblings living elsewhere (3 of 14 [21%]) or normal controls (1 of 13 [8%]). No difference in antibody frequency was found between consanguineous and non-consanguineous family members. These findings suggest that the increase frequency of lymphocytotoxic antibodies in these multiple-sclerosis patients and their family members is an indicator of the presence of a transmissible agent, probably a virus, in many patients with multiple sclerosis.


The Lewis system: New histocompatibility antigens in renal transplantation. Lewis antigen types (Le, le) were retrospectively determined in 255 first-kidney-transplant recipients. Actuarial survival of grafts at two years was significantly lower in the le/le recipients than in the Le recipients. This indicates that mismatching of these antigens contributes to rejection of kidney transplants. The effects of mismatching for the Lewis and HLA antigen systems seemed to be additive.


Matching for B-cell antigens of the HLA-DR series in cadaver renal transplantation. Stored and fresh lymphocytes from 84 donors and recipients of cadaveric renal allografts have been retrospectively typed for 7 HLA-DR antigens. The match between donor and recipient was graded as 2, 1, or 0 identities. Graft function was assessed by (i) failure or success at 3 months, (ii) serum-creatinine at 3 and 6 months, and (iii) the number of rejection episodes occurring within 3 months. All 4 recipients with 2 identities had good 3-month function, and all are still functioning at 5--19 months. Recipients with 1 identity had both a higher success-rate and better quality of function than those with 0 identities. Although the differences do not reach significance, a continuing prospective study of HLA-DR matching is justified, with particular emphasis on performing transplants where two DR antigens are shared between donor and recipient.


Normal serum-cholesterol but low H.D.L.-cholesterol concentration in young patients with ischaemic cerebrovascular disease. Serum-lipoproteins were determined in male and female patients aged under 55 who had survived an attack of ischaemic cerebrovascular disease (I.C.D.). The results were compared with findings in healthy controls. Total serum triglyceride and cholesterol concentrations were not increased. However, in the very-low-density lipoprotein fraction increased cholesterol concentrations were found, and the mean value of high-density-lipoprotein (H.D.L.) cholesterol in I.C.D. patients was 18% lower than in controls. Since a low H.D.L.-cholesterol concentration has been suggested as an independent strong risk factor, it is possible that the susceptibility of I.C.D. patients to atherosclerosis is the result of a low H.D.L. rather than hyperlipoproteinaemia.


Serum-SP1-pregnancy-specific-beta-glycoprotein in choriocarcinoma and other neoplastic disease. A radioimmunoassay for a plancental glycoprotein, beta1SP1, capable of detecting 2 microgram/l of the glycoprotein in serum was used to measure concentrations of beta1,SP1 in patients with choriocarcinoma, teratoma, colonic cancer, breast cancer, and ovarian cancer. 12 out of 94 (13%) healthy men and health non-pregnant women had detectable serum-beta1SP1 concentrations. Concentrations up to 50 000 microgram/l were found in the sera of patients with hydatidiform mole, invasive mole, choriocarcinoma, and malignant teratoma. beta1-glycoprotein concentrations were generally much lower than corresponding concentrations of chorionic gonadotrophin which is the most reliable marker for trophoblastic tumours. In a few cases, however, beta1-glycoprotein measurements may be useful in the detection of minimal residual tumour. The slightly raised values found in some patients with carcinoma of the colon, breast, or ovary seem unlikely to be useful for diagnostic purposes of for monitoring the course of these cancers.


Immunodeficiency in familial erythrophagocytic lymphohistiocytosis. 4 children with familial erythrophagocytic lymphohistiocytosis and hyperlipidaemia were found to have a previously unrecognised immunological deficiency syndrome which included defects in both humoral and cellular immunity and a plasma inhibitor of in-vitro lymphocyte blastogenesis. The inhibitory activity was proportional to the increase in the triglyceride concentration in the patients' plasma. Immunological deficiency, to which hyperlipidaemia may be a contributing factor, appears to be a significant feature of familial erythrophagocytic lymphohistiocytosis.


Treatment of idiopathic polyneuritis by a polyunsaturated fatty-acid diet. Two children, severely disabled for 6 and 12 months respectively by idiopathic polyneuritis, began to recover within a week of starting on a polyunsaturated fatty-acid diet. Recovery is virtually complete.


Mucotractive effect of lectin.

Mucotractive effect of lectin. The jackbean lectin concanavalin A caused hypersecretion of mucus in the human nose and the rat jejunum, and histology of the latter demonstrated increased emptying of goblet cells. This "mucotractive" effect has implications for the fibre hypothesis and might be therapeutically useful in patients with cystic fibrosis.


Use of chronic cerebellar stimulation for disorders of disinhibition. A review of the clinical results from 200 patients and the neurophysiological results from 42 patients suggests that chronic cerebellar stimulation (c.c.s.) can improve cerebral palsy and reduce intractable seizures. The therapeutic effects of stimulation of the cerebellar surface may not be due to activation of Purkinje cells. There is evidence that stimulation of brainstem structures, particularly the reticular formation, may be associated with thalamic inhibition; such effects would explain the clinical results of c.c.s. as well as the reduction in amplitude of reflexes, evoked potentials, and paroxysmal discharges in the electroencephalogram. This hypothesis would explain the prolonged, rebound, paradoxical, and cumulative effects of c.c.s. No clinical disturbance or significant tissue damage has resulted from c.c.s. over 5 years. The technique is an example of the therapeutic manipulation of inhibitory and disinhibitory mechanisms in the central nervous system.


Is fetal radiography really necessary?

Is fetal radiography really necessary? A survey of fetal radiographs taken in a teaching maternity hospital during one year showed that less than 10% of fetuses were radiographed. This figure could be reduced further if ultrasound were more widely available.


Severe hyponatraemia. A study of 17 patients. 17 patients with severe hyponatraemia (none had cardiac failure or had lately had an operation) all had excessively high plasma-antidiuretic hormone (A.D.H.). Only 13 had features typical of the syndrome of inappropriate secretion of A.D.H. (S.I.A.D.H.). Plasma-A.D.H. was not related to either plasma-sodium or diagnosis. There were as many patients with chest infection as with carcinoma of the lung. Plasma-sodium and plasma-A.D.H. returned rapidly towards normal in the patients with chest infection or volume depletion but these concentrations corrected much more slowly in patients with carcinoma of the lung. The increase in plasma-sodium in patients with chest infection was too rapid to be produced by water-deprivation treatment and was due to return of plasma-A.D.H. to normal. The term S.I.A.D.H. implies an understanding of pathophysiology that does not exist. As a diagnosis it does not help in management or prognosis. A simpler, more descriptive terminology such as "hyponatraemia with carcinoma of the lung" would be more useful and less confusing in the clinical situation.


Effect of histamine H2-receptor antagonists on delayed hypersensitivity. The delayed skin-test response to four antigens was assessed before and after 6 weeks' cimetidine therapy in patients with duodenal-ulcer disease. In the eight patients who received cimetidine there was a significant increase in both erythema and induration after six weeks' cimetidine therapy. In contrast, the intensity of delayed-hypersensitivity reactions at 6 weeks was not increased in eight control patients who did not receive cimetidine. These studies indicate that therapy with an H2-receptor antagonist may be associated with an augmentation of delayed hypersensitivity responses.


Prevention by bedtime cimetidine of duodenal-ulcer relapse. 45 patients with healed duodenal ulcers completed a six-month double-blind trial to compare the effects of cimetidine and placebo on the prevention of duodenal-ulcer relapse. A single bedtime dose of cimetidine (800 mg) was given and ulcer relapse was assessed endoscopically at regular intervals. At the end of the six-month trial, 16 of the 21 (76%) cimetidine-treated patients remained ulcer-free compared with only 3 of the 24 (12.5%) placebo-treated patients. No untoward effects of this treatment were observed.


An in-vitro immunological assay for diagnosis of coeliac disease. Production of leucocyte-migration-inhibition factor (L.I.F.) by peripheral-blood lymphocytes in response to challenge with gluten fractions was studied in 55 patients with coeliac disease and in 32 controls. 96% of the patients with coeliac disease demonstrated significant L.I.F. reaction in response to gluten fractions irrespective of their dietary status. Only 2 out of 32 controls had a positive reaction. This was in response to the B2 or B3 fraction, but never to both. The agarose microdroplet method of L.I.F. assay is reliable and technically simple enough for use in most clinical laboratories. The assay of L.I.F. production by peripheral-blood lymphocytes in response to gluten fractions, would be a useful adjunct in the diagnosis of gluten-sensitive enteropathy.


Long-term effects of small doses of 1,25-dihydroxycholecalciferol in renal osteodystrophy. An oral dose of 0.5 microgram of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) and 4 g of calcium carbonate was given daily to two dialysed patients and three undialysed patients in chronic renal failure with renal osteodystrophy. Treatment was given for 4-16 months. Intestinal calcium absorption became normal in all five patients. Plasma alkaline phosphatase, hydroxyproline, and immunoreactive parathyroid hormone were considerably reduced in all of the patients and in four of them these values were restored to normal. Bone histology was improved in all patients after treatment with 1,25-(OH)2D3. As well as a dramatic improvement in bone mineralisation, there was remodeling of trabecular architecture and a decrease in fibrosis in patients with initial parathyroid overactivity.


Continuous monitoring of mixed venous oxygen tension (PvO2) in cardiorespiratory disorders. The development of a miniature polarographic electrode mounted in the tip of a double-lumen plastic catheter has made possible continuous in-vivo monitoring of oxygen tension. Inexpensive catheters of this type have already proved of value as a means of continuously monitoring arterial oxygen tension in the newborn. In 25 patients with acute respiratory failure we found that these catheters could be safely and easily flow-guided into the pulmonary artery. In this way continuous recordings of mixed venous oxygen tension (PvO2) could be made for a period of several days. In our experience a sustained fall of PvO2 below 40 mm Hg proved to be a reliable indicator of respiratory or cardiac deterioration not always obvious by observation. In the patients described, falls of this order were seen after reductions in inspired oxygen concentration, in acute respiratory failure, in accidental underventilation, and in hypovolaemia and cardiac arrythmias. In some very ill patients routine nursing care involving movement of the patient caused pronounced falls of PvO2. Although electrode drift was an occasional problem, this could be checked by intermittent blood-sampling and recalibration if necessary.


Value of bile-acid binding agents in post-vagotomy diarrhoea. Cholecystectomy increases the incidence of post-vagotomy diarrhoea. The effect of agents which either bind bile acids or prevent their action on the colonic mucosa has been studied in 31 patients with post-vagotomy diarrhoea--15 had had vagotomy and pyloroplasty alone and 16 vagotomy and pyloroplasty and cholecystectomy. Cholestyramine was particularly useful after the combined operation. Aluminium hydroxide in large doses has a similar mechanism of action to cholestyramine and is cheaper and more palatable, but propranolol was of no value. This study suggests that the excretion and chemical composition of bile and the handling of bile acids by the small intestine is of fundamental importance in the pathogenesis of post-vagotomy diarrhoea.


Blood-transfusion in group-B streptococcal sepsis. Transfusion of fresh whole blood was evaluated as a means of supplying opsonins and lessening the high mortality of group-B streptococcal sepsis in neonates. Pre-transfusion and post-transfusion sera from 22 infants were examined for the presence of opsonins against group-B organisms. Opsonic activity rose only when donor blood containing heat-stable antibody was administered in high volume (greater than 40% of blood-volume). 9 of 9 infants transfused with blood containing antibody to their infecting strain survived septic episodes. 3 of 6 who received blood lacking antibody to their infecting strain died.


Calcium binding by dietary fibre.

Calcium binding by dietary fibre. Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre will reduce the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids will liberate the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity of the colon for calcium absorption.


Free-radical oxidation and antioxidants. Cells and tissues are protected against oxidising free radicals by a complexity of antioxidant mechanisms. In disease these mechanisms may fail; or the mechanisms may fail and cause disease. The primary products of free-radical oxidation undergo rapid and spontaneous fragmentation. Many of these fragments are highly active in biological systems. Some may have considerable survival value. Others are potentially lethal.


Active tuberculosis unrecognised until necropsy. 12 of the 24 cases of active tuberculosis which came to necropsy in Dundee hospitals from 1968 to 1975 were diagnosed after death. The overall distribution of anatomical types was similar to that in previous surveys, but in those diagnosed at necropsy there was an excess of psoas abscess and miliary, colonic, and adrenal lesions. Class-IV patients and a history of steroid therapy were also more common in cases diagnosed at necropsy. None of these differences is statistically significant.


Fetal wastage as a result of an alpha-fetoprotein screening programme. Amniocentesis was performed in 102 pregnancies in which maternal serum-alpha-fetoprotein (A.F.P.) concentrations were raised. 18 pregnancies were terminated. There were 15 neural-tube defects, 2 gastrointestinal abnormalities (1 of which could have been corrected by surgery), and 1 case of hydrocephaly. There was an association between raised maternal serum-A.F.P. and complications of late pregnancy including premature labour, perinatal death, and severe pre-eclampsia. After amniocentesis there was spontaneous abortion of 3 normal fetuses and 1 abnormal fetus.


Relation between plasma oestrone and oestradiol and climacteric symptoms. Plasma levels of oestrone and oestradiol-17beta were determined at 20 or 30 minute intervals for up to 24 hours in 26 postmenopausal or ovariectomised women of similar age, weight, and number of years since menopause or operation. Results in women with both superficial dyspareunia and flushes were compared with those in women with flushes only, and with those in symptomless women. Women with superficial dyspareunia had significantly lower mean concentrations of plasma-oestradiol, but not of oestrone, than symptomless women. Flushes were not related to plasma-oestrogen. The implications of these findings in relation to the optimum dose of oestrogen for treating climacteric symptoms are discussed.


Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly. 119 elderly, hypertensive patients were followed-up for 1 year and 48 for 2 years in a double-blind, randomised, controlled trial in which they received either placebo or 25-50 mg hydrochlorothiazide and 50-100 mg of triamterene daily. Half of the active treatment group also received 250 mg to 2 g methyldopa daily. After 2 years the active treatment group had an average increase in fasting blood-sugar of 9.6 mg/dl compared with an average fall of 3.1 mg in the placebo group (p less than 0.001). Blood-glucose rose by an average of 26.6 mg/dl in the active group when determined 1 hour after 50 g oral glucose and decreased by an average of 5.3 mg/dl in patients who had been on placebo for two years (p less than 0.05). The hyperglycaemic effect of diuretics appeared to be related to potassium loss since, in both groups, impairment of glucose tolerance was most marked in those in whom the serum-potassium decreased over the 2 years.


Chemotherapy of sarcoma. A comparison of three regimens. Three regimens have been used in the chemotherapeutic management of 75 adults with sarcoma. Methotrexate alone was used in 41 cases, a five-drug regimen was given in 12 cases, and adriamycin, T.I.C.-mustard, and methotrexate were given to 22 patients. Remissions, sometimes prolonged, were achieved with each regimen, and none was obviously better than the others. Because of the higher response-rate of primary or locally recurrent tumours it is suggested that sensitivity to drugs should be assessed earlier in the disease. It is proposed that a randomised study of methotrexate versus combination chemotherapy should be started in particular sarcoma subgroups, such as leiomyosarcoma and fibrosarcoma.


Misleading response of malignant gastric ulcers to cimetidine. Four patients who apparently had benign gastric ulcer (G.U.) were treated with cimetidine. The ulcers healed and their symptoms disappeared. However, when cimetidine was stopped the symptoms recurred. Intramucosal cancer was found only at histopathological examination of the resected stomachs in two of the four patients, and in all the cases malignancy had not been detected by the initial serial biopsies and brush cytology. Relief of symptoms of malignant gastric ulcers by cimetidine may delay diagnosis and appropriae treatment.


Plasma exchange in the treatment of fulminant idiopathic (autoimmune) thrombocytopenic purpura. Rapid plasma exchange in a young man with idiopathic (autoimmune) thrombocytopenic purpura and life-threatening haemorrhage acutely increased the platelet-count and enhanced haemostasis. The patient had not responded to steroids, and massive intra-abdominal bleeding had developed after splenectomy, despite numerous platelet transfusions. After plasma exchange, his haemoglobin concentration became normal without further transfusion and his abdominal girth decreased. Therefore emergency reoperation because of intra-abdominal bleeding was no longer required. A cumulative-sums plot of his platelet-count confirmed that plasmapheresis on 2 occasions was followed by a pronounced rise in mean platelet-count. Neither prednisone nor vincristine therapy altered the slope of the plot. The high initial anti-platelet antibody concentration in this patient fell after plasma exchange. These findings indicate that plasmapheresis accelerated clearance of circulating anti-platelet factors in fulminant idiopathic thrombocytopenic purpura.


Glucose-induced hyperkalaemia: A hazard for diabetics? The intravenous injection of glucose as a "therapeutic test" in comatose diabetics is reviewed in the light of evidence that it may evoke a paradoxical rise in plasma-potassium in the insulin-deprived diabetic. The plasma-potassium rose promptly after a drink of 50 g glucose in 8 insulin-dependent diabetics who had not had insulin for approximately 14-26 hours. This rise coincided with a rise in plasma-osmolality. In non-diabetic controls, however, plasma-potassium fell after the glucose drink. Osmotic and hormonal mechanisms may account for the rise in plasma-potassium in the diabetics. Since the rise in plasma-potassium may be clinically important, caution with, or abandonment of, the use of intravenous glucose as a therapeutic test is recommended.


Retention of urine in anogenital herpetic infection. In 17 patients, 15 women and 2 men, acute retention of urine developed in association with an attack of anogenital herpes. Constipation, blunting of sensation over the 2nd and 3rd sacral dermatomes, and neuralgic pains in the same area (with absence of the bulbocavernosus reflex in some individuals) suggested localised lumbosacral meningomyelitis with involvement of mainly sacral-nerve roots. The urinary dysfunction persisted on average for ten days and in 4 patients was severe enough to warrant catheterisation. Anogenital herpes should always be considered as a possible cause of acute retention of urine in sexually active young people and the possibility of occult herpetic infection of the cervix and rectum should be investigated.


Passive immunisation with serum and immunoglobulins against dental caries in rhesus monkeys. Active immunisation with Streptococcus mutans induced protection against dental caries in rhesus monkeys, and this was associated with serum antibodies. Passive transfer of immune serum with IgG, IgM, and IgA antibodies to Strep. mutans failed to induce protection against dental caries. However, when separated IgG, IgM, and IgA sera were given, IgG induced significant protection but IgA or IgM antibodies to Strep. mutans did not. IgA and IgM may compete or interfere with the protective effect of IgG antibodies, and the ratio of IgG/IgA and IgG/IgM antibodies might be an important factor in immunisation against dental caries.


Drug-associated primary acute pancreatitis. Drug histories were taken from 100 patients in their first attack of acute pancreatitis, and each was matched with a control subject of the same sex who was admitted to hospital as an emergency with acute abdominal pain, whose serum-amylase was within the normal range, and whose age was within three years of the pancreatitis patient's. The major differences between the patient groups was in the use of cardiovascular agents, and this was primarily due to a statistically significant excess of diuretic takers among the pancreatitis patients. There was an associated excess of intake of digoxin and antihypertensive and anti-anginal agents, but neither difference  was statistically significant. Other categories of drugs showed no substantial differences. The difference between the pancreatitic patients and controls is almost entirely accounted for by takers of cyclopenthiazide with potassium chloride and of frusemide, especially the former. Further clinical and experimental evidence is required before the role of diuretics and/or potassium chloride in causing acute pancreatitis can be determined.


[Peritoneoscopic diagnosis of M. Whipple--making an indirect diagnosis (author's transl)]. A case report is given of a patient with a malabsorption syndrome. Primary diagnostic procedures including x-ray examinations and endoscopy yielded no results. Alterations of the abdominal lymph vessel system were found during peritoneoscopy giving rise to the hypothetical diagnosis of Whipple's disease. This diagnosis was confirmed by intestinal biopsy yielding macrophages with PAS-positive inclusion bodies. It is pointed out, that peritoneoscopy is a good means to evaluate the abdominal lymph vessel system.


[Histochemistry of hepatitis B antigen (HBs-Ag) in routine diagnostic procedures; practical use and interpretation of findings of orcein staining (author's transl)]. The orcein staining technique was tested in 1 000 unselected liver biopsy specimens in regard to its usefulness as a routine diagnostic procedure. It turned out to be a cheap and uncomplicated screening method for HBs-Ag in liver tissue. 2.8% of the cases gave a positive result. Patients with chronic hepatitis and normal persons showing positive serological reactions for HBs-Ag could be detected by this morphological method as well. Positive results in patients with cirrhosis do allow conclusions in regard to etiology; in our group 15% of all patients with cirrhosis did show a positive result, being the biggest single group. Interpretation of findings, limits of sensitivity, theoretical considerations, and the meaning of positive results in medical expertise are discussed.


Toluidine blue staining on Epon semithin sections: effect of an oil differentiation. Semithin sections from glutaraldehyde-osmium fixed, Epon embedded tissues were stained by alkaline toluidine blue and subjected to prolonged oil treatment. This procedure resulted in progressive bleaching of sections, while a few cell structures remained highly stained. The possible mechanism of this "differentiation" effect induced by the oil treatment is briefly analyzed.


[Colorimetric investigation of microscopic dyestuffs and stainings (author's transl)]. Starting from the colorimetric data of some particular microscopic dyestuff the subtractive color spaces of a number of typical histologic stains are calculated. These results are compared with color specifications of corresponding stained preparations. Thereby, it will be tried to explain the position of color values of stained specimens on the outside of the color spaces or areas.


Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins. I. Alpha-fetoprotein induction by ethionine. The neoplastic cellular phenotype expresses many embryonic features. These features are believed to occur by derepression of embryonic genes during the carcinogenic process. A specific case is the ability of ethionine, a hepatocarcinogen, to induce an embryonic protein known as alpha-fetoprotein. A mechanism is proposed for this derepression process along with supporting evidence. It is hypothesized that the repressor protein for the alpha-fetoprotein gene must be modified (methylated) before it is functional and if for any reason this does not occur, alpha-fetoprotein will be produced. This simple theory can explain a variety of states of the liver cell in which alpha-fetoprotein is expressed namely i) fetal, ii) ethionine-treated, iii) neoplastic, and iv) tyrosinemic liver cells.


The effect of growth-promoting alpha-globulin (GPAG) on the incorporation of exogenous DNA into L-cells. I. Incorporation of isologous and heterologous 3H-DNA. Isologous and heterologous 3H-DNA (optimum concentration 25 microgram/ml of medium) are incorporated into L-cells from the medium during short-term incubation (up to 60 min). The incorporation of DNA is stimulated by a protein complex from calf serum--the growth-promoting alpha-globulin (GPAG) in the concentration 0.8 mg/ml of medium), which is rapidly taken into cells by pinocytosis. GPAG increases the frequency of incorporation of exogenous 3H-DNA into L-cells and the quantity of DNA incorporated. The quantity of 3H-DNA incorporated is further increased on the incubation of L-cells in a medium containing the complex 3H-DNA + GPAG, which is formed by the joint preincubation of the two components at 37 degrees C (20 hr); under these conditions the quantity of DNA incorporated is 150% greater than when 3H-DNA is used alone. GPAG acts as an activator of exogenous DNA transfer, stimulates its pinocytosis by the cells, and at the same time accelerates its intracellular transfer to the cell nuclei.


[The smear method for histological diagnosis of the tumors of the central nervous system (author's transl)]. The smear method for rapid diagnosis of tumors of the central nervous system at operation is not popular in this country, although this has been widely used in North America and Europe since 1930s. During the period from 1958 to 1976 we experienced 1447 histologically verified tumors of the central nervous system. This smear preparation stained by eosin and methylene blue was made for rapid diagnosis in 718 cases of them. We reviewed these cases and described microscopical findings of various kinds of tumors. In over 90% of cases the correct diagnosis will be obtained from the smears. It can be said that the smear method is appropriate for intraoperative rapid diagnosis of neurosurgical cases.


[Mitogenic activity in vitro of lysosomal proteins of peripheral blood granulocytes in patients with multiple sclerosis]. Incorporation of 3H thymidine was investigated in cultures of lymphocytes obtained from peripheral blood of 33 multiple sclerosis patients and 20 healthy controls in presence of PHA or lysosomal proteins from granulocytes. The number of T lymphocytes was determined also in the peripheral blood of these patients. A rise was observed in the mitogenic activity of proteins obtained from lysosomal granules of granulocytes of multiple sclerosis patients at the time of disease exacerbation with a fall of this activity at the time of remission. At the same time a fall of T-lymphocyte count was observed in the blood of multiple sclerosis patients. The correlations between 3H-thymidine incorporation into lymphocytes in vitro, and the mitogenic activity of proteins obtained from lysosomal granules of granulocytes and the count of T lymphocytes are discussed.


XXXIV Edward Jackson Memorial Lecture: drusen of the optic disc and aberrant axoplasmic transport. In summary, we believe that axoplasmic transport alteration is the anatomic substrate for formation of drusen of the optic disc. In familial cases the cause of axoplasmic transport alteration may be related to the presence of a genetically determined, small, crowded optic nerve head. We believe that these congenitally elevated nerve heads evolve over a period of many years through stages of atrophy and drusen formation. It appears that vascular malformations in the familial cases are primarily developmental; however, secondary vascular alterations may occur as the drusen enlarge. In retinitis pigmentosa, the drusen may be cuased by diminished production of axoplasmic material by the ganglion cell. As a general principle, chronic alterations in axonal transport from any cause seem to produce aggregates of swollen nerve fibers which impart a yellow-white appearance to the disc tissue, and account for the yellow filled-in appearance of the disc in patients with drusen, chronic atrophic papilledema and melanocytomas and, in part, for the "waxy yellow" appearance of the disc in retinitis pigmentosa.


Differentiation of irregular rhythms by frequency distribution analysis. Distinctive electrocardiographic patterns for atrial fibrillation, sinus rhythm and atrial extrasystoles, sinus arrhythmia and atrial flutter were found by analysing the frequency distribution of cycle lengths of the electrocardiogram. Frequency distribution analysis, demonstrated that atrial fibrillation is not completely irregular, but shows more long cycles than expected by chance and often a mode at the lower end of the distribution. Irregular atrial flutter is similar. Sinus arrhythmia has more variable organization, but usually there is a centrally situated mode with decreasing observations to the two extremities, and positive skewing. Examples of sinus rhythm and atrial extrasystoles usually have a mode at the upper end of the distribution with a secondary concentration of observations at the lower extremity. Ratios derived from the frequency distributions were of value in differentiating these arrhythmias. It is suggested that such information will improve computer identification of arrhythmia.


Endogenous New World primate type C viruses isolated from owl monkey (Aotus trivirgatus) kidney cell line. A type C virus (OMC-1) detected in a culture of owl monkey kidney cells resembled typical type C viruses morphologically, but was slightly larger than previously characterized mammalian type C viruses. OMC-1 can be transmitted to bat lung cells and cat embryo fibroblasts. The virions band at a density of 1.16 g/ml in isopycnic sucrose density gradients and contain reverse transcriptase and a 60-65S RNA genome composed of approximately 32S subunits. The reverse transcriptase is immunologically and biochemically distinct from the polymerases of othe retroviruses. Radioimmunoassays directed to the interspecies antigenic determinants of the major structure proteins of other type C viruses do not detect a related antigen in OMC-1. Nucleic acid hybridization experiments using labeled viral genomic RNA or proviral cDNA transcripts to normal cellular DNA of different species show that OMC-1 is an endogenous virus with multiple virogene copies (20-50 per haploid genome) present in normal owl monkey cells and is distinct from previously isolated type C and D viruses. Sequences related to the OMC-1 genome can be detected in other New World monkeys. Thus, similar to the Old World primates (e.g., baboons as a prototype), the New World monkeys contain endogenous type C viral genes that appear to have been transmitted in the primate germ line.


Genetic recombination between mouse type C RNA viruses: a mechanism for endogenous viral gene amplification in mammalian cells. A strategy based on the identification of type-specific antigenic determinants in the transitional products of gag (p15, p12, and p30 proteins), pol (reverse transcriptase), and env (gp70 glycoproteins) genes of mammalian type C viruses has been used to study genetic recombination between these RNA viruses. By this approach, recombinants involving exogenous and endogenous mouse type C viruses have been identified and genetically mapped. Analogous techniques have been applied to investigate the genetic relationships between different classes of endogenous virus that exist within  the same mouse cells. Proteins of the inducible class of xenotropic virus were shown to exhibit extensive antigenic homology with the gag but not the env gene products of the ecotropic virus class. Instead, the env gene-coded glycoproteins of the inducible and noninducible xenotropic virus classes possessed striking antigenic relatedness. These results, as well as supporting findings from molecular hybridization, favor the concept that the inducible xenotropic virus of mouse cells arose by a recombinational mechanism involving the progenitors of the other two endogenous virus classes.


The spectrophotometric determination of streptomycins. The spectra produced by the acid treatment and alkaline treatment of streptomycin and dihydrostreptomycin have been investigated to obtain suitable methods for their determination. Mixtures of the two antibiotics have been successfully determined in the UV region. Thus, using the orthogonal function method, dihydrostreptomycin has been determined after acid treatment whereas streptomycin has been determined after alkaline treatment followed by immediate neutralization.


High-resolution chromosome analysis in clinical medicine. The field of human cytogenetics has expanded considerably in the past few years due, to a large extent, to the application of the metaphase banding techniques. Among many advances, the chromosomal abnormalities involved in over thirty newly discovered syndromes have been defined and consistent chromosome defects have been observed in several neoplasias. Very recent improvements in culture techniques through cell synchronization and in chromosome treatments, such as the use of minimal exposure to colcemid and/or the use of agents that inhibit chromosome condensation, allow for the routine utilization of highly elongated and finely banded prophase chromosomes. These new techniques are being used clinically to uncover previously undetectable chromosome defects, to localize the exact break points involved in numerous duplication-deficiencies known in man, and to establish possible phenotype-genotype relationships at a refined level.


[Complement system in disseminated lupus erythematosus]. The levels of C3, C4 and CH50 in patients with lupus erythematosus disseminatus (LED) were lower than in the controls. However, although in many patients these levels were below the normal values, there was no statistically significant difference between the two group. The levels are reduced during the acute phases and in some patients they remain high. On the whole, C3 was lower in patients with nephropathy (p less than 0,025) than in patients presenting with clinical activity (p less than 0,02). The positive relationship existing between C3 and C4 (r = 0,641, p less than 0,01) suggests activation of the complement system in LED via the classic route. In cases with concurrent lupus nephropathy a relationship between C3 and C3PA was seen, suggesting that in this case the alternative route is involved.


In vitro sensitization and mast cell degranulation in human jejunal mucosa. Sera from 3 allergic patients with specific IgE antibodies as shown by RAST were used to sensitize jejunal mucosa obtained from surgical patients. The sensitized specimens were challenged with the appropriate antigens to the specific IgE shown in the sera, Non-challenged sensitized specimens were used as controls to determine mast cell degranulation. The mast cells were counted in a defined area in the mucosa immediately adjacent to the muscularis mucosa. Mast cell degranulation was 47 percent in a timothy pollen system, 40 percent in an eggwhite system, and 33 percent in a codfish system. The results of the investigation indicates that mast cells in the human jejunal mucosa are able to react in the same manner as mast cells in the human lung. The experimental model described appears suitable for studying the allergic reaction in the gastrointestinal tract and the effect of pharmacotherapy in this respect.


Strong association between the HLA-Dw3-related B cell alloantigen -DRw3 and coeliac disease. The frequency of HLA-A, -B, and -C antigens, of -DRw3 and the associated B-lymphocyte alloantigen -DRw3 has been studied in 68 children with coeliac disease (CD). CD was found to be primarily associated with the B-lymphocyte alloantigen, the relative risk being calculated to 54. The possible relation between the B-lymphocyte alloantigen DRw3 and -Dw3 is discussed. The high relative risk and the fact that 95% of the patients with probable or definite CD had the B-lymphocyte alloantigen DRw3, underline the diagnostic value of B-lymphocyte typing in coeliac disease.


Urine proteins in renal disease. II. Alpha 2-microgiobulins in tubular proteinurias with special reference to endemic nephropathy. Urine microglobulins were analyzed in 145 patients with a variety of chronic renal disease, 58 of whom had endemic nephropathy. On agarose-gel electrophoresis, the urinary-protein patterns of either tubular or mixed tubulo-glomerular type invariably showed two to three discrete alpha 2-migrating bands differing slightly in net charge. Marked differences in their relative concentrations occurred from one case to another and, following prolonged storage at 4 degrees C, in the same urine as well. All three fractions showed only a single precipitation line on immunoelectrophoresis when tested against antisera to urinary proteins; thus it would appear that they represent differently charged, but antigenically identical molecular forms of a protein of low molecular weight. The results also suggest that their detection might be used as an indicator for clinical purpose of impaired tubular function.


Dynamics of the interaction between Entamoeba histolytica and components of the immune response. I. Capping and endocytosis; influence of inhibiting and accelerating factors; variation of the expression of surface antigens. The possible implications of cell membrane dynamics in the host--parasite relationship has been studied. Entamoeba histolytica rapidly redistributed and internalized antibodies and Con A bound to its surface. The process was dependent on temperature, cell metabolism and changes of pH in the environment. Phagocytizing amoebae displayed a higher rate of membrane perturbations, which were similarly affected by temperature, cell metabolism and pH variations. Cytochalasin B partially inhibited the redistribution whereas colchicine did not. Colchicine in combination with Cytochalasin B augmented the inhibitory effect of Cytochalasin B alone. The expression of antigens at the surface of the amoeba showed cyclic fluctuations during cell growth.


Subtypes of HBsAg among hepatitis patients. Serum samples from 94 Finnish hospital patients with hepatitis B were investigated for subtypes of HBsAg. Subtype ay predominated in patients with acute hepatitis (77%). All drug abusers had the ay subtype. Of 11 patients with chronic liver disease, 10 (91%) had the ad subtype. Five of 7 hepatitis cases associated with blood transfusion had subtype ay, although this determinant has not been detected among Finnish non-paid blood donors. These results suggest that blood donors who incubate hepatitis B (HBsAg not yet detectable) are an important source of transfusion hepatitis.


R-factor involvement in a local outbreak of ampicillin-resistant Haemophilus influenzae infections. In a Swedish nursery 11 of 15 children harboured non-encapsulated Haemophilus influenzae in their nasopharynx. Six children had ampicillin-resistant and beta-lactamase-producing isolates. Five of these children had otitis whereas one was healthy. In order to identify the origin of the H. influenzae isolates their O-antigen determinants were studied by an immunodiffusion technique. 18 different rabbit antisera were used. For each isolate an O-antigen pattern was recorded. Five of the 6 resistant isolates had the same O-antigen pattern, indicating that their origin was one strain. The 6th isolate was from another strain. Different isolates from the same strain were found to be either sensitive or resistant to ampicillin. In one child the H. influenzae lost its resistance during trimethoprim-sulphamethoxazole treatment. It is concluded that an R-factor may have been involved in the distribution of ampicillin resistance in the H. influenzae studied. Previous in-vitro studies have shown that beta-lactamase production can be transmitted by a plasmid among H. influenzae strains.


A simple photometric method for determination of blood loss during transurethral surgery. A new method for determining blood loss during transurethral operations is presented. Its basic principle is photometry of blood concentrations in haemolysed irrigating fluid. At test study was run on 50 patients who underwent transurethral prostatic resection because of hyperplasia. The photometer was of a type commonly used for routine determination of a haemoglobin concentration in blood. The apparatus for the test is therefore readily available. The test is simple to perform and gives highly reliable results within a few minutes. In seven cases double sampling was done. Since the results within each pair of samples were practically identical, double sampling was considered superfluous for the rest of the case series. Visual estimation of blood loss during transurethral operations seems to be customary in most urologic units in Sweden. We found this method to be unreliable, with underestimates of about 100% in several cases.


[Therapy resisting pains. Drug therapy of cancer pain]. A pain may seem to resist all kinds of therapy without necessarily being absolutely refractory to treatment. The factors are discussed which may contribute to the "refractoriness" of a pain to therapy in the area of pain due to carcinoma, i.e. lack of understanding of modern pain concepts, inability to diagnose pain as due to conversion, failure to recognize the influence of the affects anxiety, hopelessness etc. on pain intensity, administration of analgesics in situations where another form of therapy would be indicated, e.g. plexus blockade, and insufficient knowledge of the effects, side effects, dosage and timing of the administration of mild analgesics, neuroleptics, antidepressives and narcotics.


Transcutaneous electrical nerve stimulation in the management of pancreatitis pain. The application of transcutaneous electrical nerve stimulation (TENS) to the abdomen produced prompt and sustained relief of the pain associated with pancreatitis in five patients and in another patient with probable acute pancreatitis. The disorder was acute in two patients and recurrent in four. Multiple hospitalizations, including the need for analgesics and opiates, had been required during previous attacks in five patients. In view of the simple and noninvasive nature of such treatment, more extensive clinical trials appear to be warranted. Some of the possible mechanisms of action for TENS analgesia are reviewed.