Circulating thymic-hormone activity in congenital immunodeficiency. Circulating thymic-hormone activity was assayed by measuring Thy 1-2 antigen induction on null lymphocytes from athymic mice incubated with human plasma or serum. Plasma from 19 normal children aged under 10 had inductive activity equivalent to 10-6-16-2 ng thymopoitin/ml. Plasma from 15 infants were severe combined immuno-deficiency, 2 of whom had appreciable immunoglobulin synthesis, and from 2 infants with DiGeorge syndrome had little or no inductive activity. Successful reconstitution with thymus or bone-marrow grafts and with red-cell infusions (if adenosine-deaminase deficiency is present) was followed by a rise in circulating thymic-hormone activity.


Frequency of eye complaints and rashes among patients receiving practolol and propranolol. Among 71 patients treated with practolol by general practitioners, eye complaints were recorded in the case-notes of 14 (20%) during treatment, compared with 4 (6%) during equal periods before the drug was prescribed. Half the patients with eye complaints also had a rash while receiving practolol. These findings, which were not due to greater numbers of attendances during treatment nor to awareness of the hazards of the drug, suggest that mild eye complaints were relatively common among patients treated with practolol. Among 246 patients treated with propranolol, the numbers with eye complaints before and during treatment were similar, although there was a significant excess of patients with both an eye complaint and a rash during treatment.


Immunoglobulin-containing cells in multiple-sclerosis plaques. An immunoperoxidase method has been used to study the content of immunoglobulin-containing cells in 100 multiple sclerosis (M.S.) plaques and 100 adjacent areas of normally myelinated tissue obtained post mortem from ten patients with M.S. Immunoglobulin-containing cells were significantly more numerous in plaques than in non plaques and in recent plaques as compared with old plaques. More of the cells in plaques contained demonstrable light chain than heavy chain, and the kappa/lambda ratio was significantly higher in recent and moderately recent plaques than in normally myelinated tissue. 92% of the demonstrable heavy chain present in cells was IgG, 7-3% was IgA, and 0-7% IgM. It is suggested that each plaque in M.S. may be associated with local proliferation (a clone or small number of clones of immunoglobulin-producing cells, producing predominantly IgG heavy chains with kappa light chains, and occasionally with lambda light chains.


Modified Makari skin test in follow-up of bladder-cancer patients. 123 patients who had been treated for carcinoma of the bladder and who were clinically recurrence-free at the time of their initial Makari skin test are being followed-up; 77 were negative and 46 positive. 48 of these patients have been followed-up so far, for 3-9 months, with cystoscopic review and repeat Makari testing; 75 have still to be followed-up. The high initial positive rate of 37% has been largely explained by the discovery of a recurrent tumour at the first cystoscopy after the test. The concordance between tumour status and repeat Makari testing indicates its ability to detect early recurrence.


Breath-methane in patients with cancer of the large bowel. In 30 patients with cancer of the large bowel, 24 (80%) had detectable levels of methane in their breath, compared with 25 (39%) of 64 patients with non-malignant large-bowel disease and 83 (40%) of 208 subjects without large-bowel disease. These findings suggest that there may be a difference in anaerobic intestinal flora between patients with cancer of the large bowel and those without the disease. This difference may antedate the development of the tumour or, alternatively, result from the tumour.


Hypercapnia during oxygen therapy in acute exacerbations of chronic respiratory failure. Hypothesis revisited. A modification is proposed to the well-known hypothesis which explains the development of progressive carbon-dioxide retention in patients with acute exacerbations of chronic respiratory failure when they are given supplementary oxygen to breathe. It is suggested that, in these patients, increased production of lactic acid by the brain, due to profound hypoxia, leads to a central hypoxic drive to breathing which is absent in remission when the arterial oxygen tension is higher. Evidence from the literature in support of this modification is sought by comparing the respiratory response to oxygen of patients in an acute exacerbation of respiratory failure with the response of patients in a chronic stable state. Three patients are described in whom the response to oxygen during an acute infective episode was very different from their response when in remission.


Sexual knowledge and attitudes of Southampton medical students. A survey of three groups of medical students at the University of Southampton--each group being at a different stage in the course--was carried out in order to establish how far sexual attitudes and knowledge were influenced by the curriculum. Few changes in attitude were recorded, but knowledge of sexual matters was found to have increased in the students who had completed the third year of the course, compared with the level of knowledge assessed in those who were about to begin their course or who had completed the first year. As a result of the survey, some changes have been made in the undergraduate curriculum.


[Whipple's disease--a case of undiagnosed malabsorption with fatal outcome (author's transl)]. A patient is described who died from malnutrition due a rare but readily diagnosable malabsorption disorder for which effective therapy is available. "Terminal carcinomatosis" should not be diagnosed without histologic documentation; a treatable condition may be present instead.


[Active enhancement of canine liver allograft by pretreatment with polyspecific spleen alloantigen (author's transl)]. Because it is not possible to use donor specific antigens for the induction of immunological enhancement in cadaveric organtransplantation, attempts were made to use polyspecific antigens in the enhancement of orthotopic canine liver allotransplants. Of 34 mongrel recipients, 17 controls survived for 6.9 +/- 1.5 days. Six recipients (group 3) were given 750 mg/kg polyspecific, semisoluble antigen prepared from 20 spleens (PSEA 20) together with 10 mg/kg prednisolone on days 15, 8 and 1 before transplantation. The mean survival time of this group was 10.1 +/- 2.0 days (P less than 0.01 compared with the control group). Six other recipients (group 4) were treated similiarly, except that the antigen had been prepared from a pool of 70 spleens (PSEA 70). Survival was variable here: 3 survived for more than 3 weeks and the other 3 died on days 1, 7 and 8 post-operatively, with signs of accelerated rejection. Donors and recipients were not identical for LD determinants, but one donor recipient pair with near identity showed a higher degree of enhancement. The recipients displaying accelerated rejection had markedly higher lymphocytotoxic and haemagglutinating antibodies. Animals surviving for longer periods had low antibody titres. In addition, all recipients progressive rejection were found to show inhibition of leucocyte migration. After three antigen doses rosette-forming lymphocytes were present in increased numbers in peripheral blood, and remained unchanged thereafter.


[Pathology of liver failure and hepatic coma (author's transl)]. Liver failure and hepatic coma present with various clinical and morphological counterparts. While fulminant viral hepatitis is the most common cause of acute liver failure, liver cirrhosis with vascular bypass most often is responsible for the hepatic coma in chronic diseases. Prognosis is mainly determined by the extent of liver cell necrosis and regeneration, provided extrahepatic complications do not cause death. Prognosis can best be judged by stereology of liver biopsies and determination of the alpha-fetoprotein.


Less common side effects of methyldopa.

Less common side effects of methyldopa. A patient with methyldopa-induced hyperpyrexia who also developed positive antinuclear factors, LE cells and ocular disturbance is described. These side effects disappeared when the drug was withdrawn. The incidence of these side effects is reviewed. Methyldopa should be withdrawn when these side effects appear, as less troublesome antihypertensive drugs are now readily available.


Paediatric assessment centres in Great Britain: implications for Australia. Assessment centres have become a prominent feature of paediatrics in the United Kingdom. Staffed by a developmental paediatrician and a team of medical and paramedical workers they are valuable for the diagnosis and coordination of management of handicapping conditions in childhood. Both local and regional assessment centres should be established. In the first instance these should be in conjunction with teaching children's hospitals in major cities in Australia.


Uses of percutaneous electrical stimulation of the nervous system. Temporary percutaneous electrical stimulation of peripheral nerves and the spinal cord is a valuable screening technique. This approach will  provide a much higher success rate for identifying those patients suitable for a permanently implanted stimulation system. The system appears to be the treatment of choice for chronic, intractable pain caused by nerve injury. The author presents his surgical procedures for stimulation of peripheral nerve and spinal cord. A summary of clinical results is discussed.


Towards a unified theory for immunogenetic systems. Some selected properties of ABC- and AB-D reaction patterns generated by S3 and T3 universes. The principles of a radically new unified theory and a unified but fundamentally theory-invariant classification system are described and exemplified for immunogenetic systems. The classification system permits a differentiation of immunogenetic systems into 15 qualitatively distinct classes with quantitative subsets when tested against two reagents. It can easily be expanded into a n-reagent taxonomy. The theory logically explains a set of selected and previously more or less "unexplainable" properties and their (even more unexplainable and probably previously unnoticed) associations in two main classes of immunogenetic systems, the ABC- and AB-D systems. The associated properties discussed are the presence (+) or absence (-) of: 1. antithetical alleles; 2. dosage effects; 3. inherited "strong" and "weak" antigens; 4. "silent" or "amorphous" genes. In ABC- systems, properties 1 and 2 are present while 3 and 4 are absent or extremely rare (i.e. 1+2+3-4-). In AB-D systems, properties 1 and 2 are absent while 3 and 4 are present (i.e. 1-2-3+4+). Through the design of hypothetical immunogenetic universes (HIU), these property associations are shown to be produced by the contemporary (simple-complex) framework-dependent transformations of experimental observables/matrix facts and not by any corresponding associated properties present in the input HIU in themselves.


[The effect of oral contraceptives on levels of thyroid hormone, blood coagulation and ceruloplasmin (author's transl)]. The effect of various hormonal contraceptives on the thyroid hormone level, plasmatic and thrombocytic coagulation, cholesterol and ceruloplasmin levels and the activity of gamma-glutamyl transpeptidase was investigaged by the changes produced by long term cyclic estrogen-gestagen therapy on the metabolism of the organism. The free thyroxine index and the total cholesterol were within the normal range. The thyroxine binding index at 44% was above the normal level and the mean value was significantly raised. The ceruloplasmin concentration in the serum was also significantly increased. Pointers to a general hypercoagulability could not be ascertained with a statistical significance.


[Incurable colorectal cancer. Possibilities and limits of differentiated therapy (author's transl)]. The different palliative procedures in incurable colorectal cancer are critically reviewed. In regard to the progress in operative and non-operative management the aims and possibilities have to be newly defined. The alternative, colostomy or enteroanastomosis, is unable to satisfy higher demands. This also means a tendency to aggressive resection therapy in colonic and proximal rectal carcinoma as well as combined local surgical and radiological treatment in distal rectal cancer. In emergency cases the minimal intervention necessary has to be planned in preparation for a more radical effort later on. The role of chemotherapy in colorectal cancer is still not precisely defined. In complications where surgical or radiological palliation is hopeless, the limited success of a combined therapy with 5-fluorouracil and MeCCNU seems justified.


In vitro immune responsiveness to vaccinea virus and HLA. Because several lines of evidence suggest that HLA products might have an important function in the immune response to infectious agents, we studied the possible relation between immune response to vaccinia virus and HLA phenotype in 79 soldiers who received a primary vaccination. A low in vitro response to vaccinia virus was associated with HLA-Cw3 both in 49 subjects tested three to four weeks after vaccination (P less than 0.001) and in the remaining 30 subjects tested five to 11 weeks after vaccination (P = 0.035). Responses to unrelated antigens and phytohemagglutinin of lymphocytes tested before, three to four weeks and five to 11 weeks after vaccination indicated that this association was specific for vaccinia virus and suggested that differences in immune response to vaccinia were reflected in temporarily altered immune responsiveness to unrelated antigens. Our results indicate that HLA-Cw3 or an HLA product associated with Cw3 is involved in the cellular immune response to vaccinia virus.


Ventricular premature beats and mortality after myocardial infarction. To assess the role of ventricular premature beats in influencing mortality of coronary patients, 1739 men with prior myocardial infarction were monitored for ectopic activity for one hour at a standard base-line examination, and followed for mortality for periods up to four years (average, 24.4 months). Analyses of survival taking into account other important prognostic variables establish that the presence of complex premature beats (R on T, runs of 2 or more, multiform or bigeminal premature beats) in the monitoring hour is associated with a risk of sudden coronary death three times that of the men free of complex ventricular premature beats. The corresponding risk of death from any cause is twice that of men without such complex beats in the hour. These arrhythmias make an independent contribution to increased risk of death that persists over the length of this observation period.


DNA complementary to parathyroid mRNA directs synthesis of pre-proparathyroid hormone in a linked transcription-translation system. DNA complementary in sequence to the messenger RNA for pre-proparathyroid hormone was synthesised using reverse transcriptase. In a linked transcription-translation system using RNA polymerase and cell-free extract from wheat germ, the DNA directed the synthesis of a protein identified as pre-proparathyroid hormone by N-terminal sequencing and by electrophoretic and immunologic criteria.


Distribution of acridine orange-stained RNA in neuroblastoma cells during differentiation. Vital staining of neuroblastoma cells with acridine orange produces a bright intracellular red-orange fluorescence most probably due to the occurrence of RNA. The distribution of this fluorescence depends on the state of morphological differentiation. The fluorescence is predominantly found in the perikaryon, the growth cones, and the endings of the processes of differentiated cells. This is of special interest in respect to the biochemistry of differentiation and the function of nerve cells. Comparative autoradiographical studies with 3H-uridine demonstrate that the newly synthesised RNA is transported into the endings of the cell processes.


A distinctive antigen present in liver carcinomas induced by 3'-methyl-p-dimethylaminoazobenzene. Hepatocellular carcinomas and cholangiocarcinomas induced in rat liver by the administration of 3'-methyl-p-dimethyl-aminoazobenzene (3'-Me-DAB) were found to contain a carcinoma distinctive antigen by immunofluorescence, immunoelectrophoresis and immunodiffusion. This carcinoma distinctive antigen does not appear to be alpha-fetoprotein (AFP) or the preneoplastic antigen.


Immunological studies of induced tumors of the rat submandibular gland. The antigenic activity of rat submandibular gland carcinoma induced by 9,10 dimethyl-1,2 benzanthracene (DMBA) has been evaluated using rabbit antisera to normal submandibular gland extract and to extracts of the induced tumors. Extracts of all tumors and premalignant lesions show reduction in the concentration of several of the intrinsic antigens of the normal submandibular gland when they were evaluated by immunodiffusion and immunoelectrophoresis. Although all the induced tumors, including those used for antisera preparation, are well-differentiated epidermoid carcinoma, a considerable variation is present in the antigenic pattern of each tumor. When antisera to several tumors, absorbed with rat serum and kidney extract, were used in studying extracts of all induced tumors, antigenic bands were observed. The number of these bands varies from three to five. All the induced carcinomas share the presence of two of these bands in the alpha and beta-globulin region, the remaining bands differ from one tumor to another.


The effect of several antitumor agents on 3H-TTP incorporation in host liver and hepatoma nuclei. Six different tumor antibiotics have been investigated in a nuclear incorporating system for their ability to inhibit 3H-TTP incorporation. Both host liver nuclei and nuclei prepared from two different Morris hepatomas have been used in the investigation. Three of these anti-tumor agents inhibit 3H-TTP incorporation equally in host liver and hepatoma nuclei, two preferentially inhibit incorporation in hepatoma nuclei and one stimulates incorporation preferentially in host liver nuclei. The effects of these compounds on nuclear DNA has been analyzed on neutral and alkaline sucrose density gradients. The nuclear incorporation system appears to be useful as a screening test system for potential anti-tumor agents.


Serum alphafetoprotein in bladder carcinoma. 112 cases, of varying ages, which were diagnosed as having carcinoma of the bladder by cystoscopy and biopsy from the tumor, were investigated for the presence of alphafetoprotein (AFP) in the sera. 59 (52.6%) out of the total, showed positive results, and no false positive results occured. Radioimmunoassay was capable of increasing the positivity rate still further. All of the cases were proved by liver scan and laparotomy to be free of metastasis, but all had bilharziasis during childhood, in which there is no factor affecting the liver that is responsible for the release of AFP, as the only species of bilharziasis present in Iraq is that of hematobium.


Immunodiagnostics of malignant diseases. II. The electrophoretic mobility test in the diagnosis of gynecological malignancies. We applied the electrophoretic mobility test (EMT) to 117 patients. 49 patients suffered from gynecological malignant tumors of different types and eleven had a carcinoma in situ. 57 patients served as a control group, 26 of whom were clinically healthy volunteers and 31 had benign gynecological diseases. In the EMT all malignant cases had inhibition values of at least-5% or even more. All other tested persons, the so-called non-malignant or healthy cases, had an inhibition of less than -5% or even an acceleration of the tanned sheep erythrocytes stabilized with sulfosalicylic acid (ETS).


Collagenase activity in the human umbilical cord. By means of a tissue culture assay the activity of the collagenolytic system of ten human umbilical cords was estimated. I found collagenolytic activity in the dimensions of about 10(-3) units of collagenase by comparing the tissue explants with known collagenase concentration on filter paper. EDTA, which is known to inhibit collagenases from human granulocytes, did not prevent the lysis. Normal human serum in a concentration of 1 mg/ml was found to inhibit the enzyme effect up to 36.34% (mean percentage of inhibition 29.67%). It is supposed that the rest of the activity is due to a tissue collagenolytic system. The whole activity was only by o-phenanthroline to be prevented. As a result can be said that the regression of the human umbilical cord is not primarily mumification but due to the activity of the collagenolytic enzyme system.


[Therapy of purulent meningitis with immunglobulins] (author's transl)]. The finding of 53% disturbances in synthesizing bacterial antibodies and 88% disturbances in opsonizing in children with purulent meningitis was the reason for therapy with immunglobulins. Intravenous Gammaglobulin (Gammavenin) was used in 26 children with purulent meningitis, 1 ml/kg/d through 3 days. The liquor cell count was in all patients 48 hours after starting of treatment 20% or less, there was no death, 2 children showed neurological defects.


Respiratory complications of primary hypogammaglobulinemia. The primary hypogammaglobulinemias, with onset of acute and recurrent bacterial infections in infancy and early childhood, consist of a heterogeneous group of largely genetically determined antibody deficiency states including that congenital sex-linked form, Bruton's agammaglobulinemia. Patients with panhypogammaglobulinemia require continuous gamma globulin therapy; in spite of this, they continue to develop infections of the upper and lower respiratory tract in the form of otitis media, mastoiditis, sinusitis, rhinitis, pharyngitis, tracheobranchitis, or pneumonia of a chronic and recurrent nature. The frequency and severity of these infections vary from patient to patient. These episodes all respond to antibiotic administration, often with a prolonged course. Many patients develop permanent pulmonary sequelae in the form of atelectasis, bronchiectasis, and pulmonary fibrosis. Most of these changes involve focal areas of the lower right middle and left lingular lobes. Occasionally, the patient may develop generalized bronchiectasis but without hilar lymphadenopathy. Management emphasizes early detection, early institution of gamma globulin treatment, and administration of appropriate antibiotic therapy at the earliest onset of infection. Good pulmonary toilet, nutritional care, emotional care, and a loving home environment are of utmost importance. These patients should be followed in a medical center with the joint effort of specialists in various disciplines.


Effect of specific teaching techniques on cognitive learning, transfer of learning, and affective behavior of nurses in an in-service education setting. To test the effects of different teaching techniques on learning, transfer of learning, and affective behavior of nurses, three hypotheses were developed based on Gagne's Theory of Knowledge Acquisition, Ellis' Theory of Transfer of Learning, and Bloom's Theory of Affective Consequences of Knowledge. The hypotheses tested were that an experimental (E) group will learn, transfer, and demonstrate affective behaviors significantly more than control groups. Subjects were 131 staff nurses. The E group (N=36) was taught by means of filmstrip with discussion (FD). Control groups II, III, and IV (N=33, 31, and 31 subjects, respectively) were taught by means of lecture alone (L), lecture with discussion (LD), and filmstrip alone (F), respectively. The content taught was Engel's Theory of Grief and Mourning Process. Pre- and posttests were done to obtain measures on learning and transfer. Results showed that the E group transferred significantly more than the L group; in general, all groups showed significant increases in learning and transfer; film groups transferred significantly more than the lecture groups; subjects preferred LD and FD significantly more than F or L. Implications were made for education of patients, students, and staff.


Synthesis of full-length DNA copies of avian myeloblastosis virus RNA in high yields. The synthesis of full-length complementary DNA copies of avian myeloblastosis virus RNA is described. The cDNA is estimated by electrophoresis in agarose-methylmercury gels to have a molecular weight of 2.6 X 10(6), equivalent in size to that of the RNA template. Most (60-70%) of the reaction product is the full-length material and yields correspond to 60-70% of the input RNA.


Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Rat immunoglobulin E (IgE) was treated with a crosslinking reagent, dimethyl suberimidate, and fractionated by gel filtration into monomers, dimers, trimers, and higher polymers. The fractions retained substantial ability to bind specifically to mast cells. About one-third of the cell-bound dimers appeared to bind bivalently. The fractions were assayed in vivo by passive cutaneous anaphylaxis in rats, and for histamine or serotonin release in vitro using normal or tumor mouse mast cells. The monomers showed no activity, while the dimers and higher polymers gave excellent and approximately equivalent responses. We conclude that IgE that has been crosslinked to form dimers prior to the addition to mast cells can serve as a unit signal for triggering IgE-mediated exocytosis.


Cleavage of C2 by C1s into the antigenically distinct fragments C2a and C2b: demonstration of binding of C2b to C4b. The activation of complement component C2 by C1s is a major reaction step leading to the assembly of two related macromolecular enzymes in the classical complement pathway C3 convertase and C5 convertase. The present studies clearly document the smaller fragment, C2b, that results when human C2 reacts with C1s. We have identified and characterized C2b (34,000 daltons) as a single protein on disc electrophoresis and immunoelectrophoresis. C2a (73,000 daltons), the larger fragment from this reaction, has a more acidic nature and C2b is more basic. These fragments can also be detected by their different antigenic determinants. When the C2-C4b complex is activated in the fluid phase by C1s and allowed to decay, it dissociates into C2a and the C2b-C4b complex. Furthermore, when C2 is bound to C4b-Sepharose and then reacted with C1s, only the C2a fragment is released from the solid phase C2-C4b-Sepharose into the fluid phase, and the C2b fragment remains noncovalently bound to C4b-Sepharose. These results suggest that the C2b portion of C2 contains a stable binding site for C4b and, after the decay release of C2a from this C3 convertase, the C2b fragment remains bound. Thus, the decay release of C2a may represent a temperature-dependent dissociation from C2b.


Specificity studies on cytotoxic thymus-derived lymphocytes reactive with influenza virus-infected cells: evidence for dual recognition of H-2 and viral hemagglutinin antigens. Cytotoxic thymus-derived (T) lymphocytes were readily detected in spleens of mice inoculated intranasally with mouse-adapted A/Port Chalmers (H3N2), A/England (H3N2), A/PR/8 (H0n1), and B/Hong Kong influenza viruses. T-cell-mediated lysis of H-2 compatible target cells infected with the strain of virus used to immunize the mice was considerably higher than lysis of either syngeneic cells infected with a different strain of influenza virus or allogeneic cells infected with the immunizing strain of influenza virus. The findings that cytotoxic lymphocytes can distinguish minor antigenic variants among influenza viruses and that lysis depends on H-2 histocompatibility between lymphocyte and target cell support the concept of dual recognition of visual and H-2 histocompatibility antigens in T-cell-mediated antiviral immunity.


[Bronchial carcinoma. Problems and treatment with special reference to radiotherapy (author's transl)]. With reference to the recent literature, a representation of case-history, therapy and prognosis of bronchial carcinoma is made. Inhalation of tar products by smoking, as well as predominantly occupational dust are the important etiological factors for the increase in bronchial carcinoma. Because of the long occult progression of the disease the diagnosis based on clinical symptoms is made very late. Only a greater effort in organisation and diagnostics permits an early detection in high-risk groups. Therapeutic success has remained constant since the sixties. Up to now only the consequent pre-operative selection of patients has been significant for improvement of surgical results. Five-year cures are more frequent after lobectomy than after pneumonectomy. In radiation therapy, the use of high-voltage gamma rays in contrast to conventional deep radio-therapy, has not brought any significant improvement. An additional intensive and individual care and follow-up of patients is of vital importance. The optimal curative radiation dose is 6000 rad. Particularly pre-operative irradiation is important to prepare some inoperable patients for curative surgery. Postoperative radiation therapy is also valuable for doubtful radical surgery and after exploratory thoracotomy. Palliative radiation therapy results in rapid disappearance of symptoms; with generalized disease or in suspicion for formation of metastases, chemotherapy should be preferred. This is particularly true for anaplastic, small and large cell carcinomas, and their rapidly growing metastases. In those cases, combination of polychemotherapy may decrease the tumor size and increase the length of remission. The prognosis depends on microscopic tumor type, stage of the disease, and therapy. Abnormal excretion of steroids and immunological disturbances are prognostic at the time of diagnosis.


Variable effects of corticosteroid treatment of serum enzyme activities in Duchenne's muscular dystrophy. Corticosteroid administration on alternate days to five boys with Duchenne's muscular dystrophy (DMD) lowered the high serum creatine kinase and lactate dehydrogenase activities in three, caused no change in one, and increased these activities in one. These observations indicate that, as given, this therapy can partially normalize a major biochemical abnormality of this disease in some but not all patients with DMD.


Macrophage-dependent response of immune human T lymphocytes to PPD in vitro. Influence of HLA-D histocompatibility. The proliferative response of immune human T lymphocytes to low concentrations of purified protein derivative (PPD) in vitro was found to require the presence of macrophages. By coculturing different combinations of immune T lymphocytes and allogeneic macrophages with PPD in low concentration, optimal stimulation (that is, as efficient as the autologous combinations) was shown to require HLA-D identity between the macrophages and responding T cells. Identity for HLA-A and -B appeared to be of less or no importance. It is concluded that membrane structures encoded by HLA-D or closely linked loci are involved in the human macrophage/T-lymphocyte interaction in the proliferative response to PPD, much in the same way as the Ia antigens of rodents.


Activation of human suppressor cells in mixed lymphocyte cultures. Lymphocytes transferred from 6-day-old human mixed lymphocyte cultures (MLC) inhibited the response to allogeneic cells of freshly taken lymphocytes autologous to the transferred MLC-responding cells. No specificity for this cell-dependent suppression could be determined. The inhibitory effects of the suppressing cells could be abrogated by moderate X-ray irradiation and significantly reduced by pretreating them with an anti-Ia-like antiserum and complement. The human suppressor cell responsible for the observed effects therefore appears to carry determinants equivalent to the murine Ia alloantigens.


Immunoglobulin deposits in the dermo-epidermal junction zone in patients with systemic lupus erythematosus. Rheumatoid arthritis and temporal arteritis compared by serological testing including alpha2-macroglobulin. In biopsies from normal-looking skin, immune complexes in the dermo-epidermal junction zone were found by a direct immunofluorescence technique in 14 of 17 patients with systemic lupus erythematosus, in 6 of 12 patients with rheumatoid arthritis, but in none of 10 patients with temporal arteritis and 25 normal controls. Blood samples were obtained simultaneously from all patients and high titres of IgG organ-nonspecific antinuclear factors with complement-fixing properties were found to be closely related to systemic lupus erythematosus. IgG granulocyte-specific antinuclear factors were related with rheumatoid arthritis, while high concentrations of plasma fibrinogen were characteristic of temporal arteritis. No significant increases or differences in blood values of alpha2-macroglobulin were found between the groups and no correlation was found with deposits in the skin.


Adjunctive therapy in treatment for head and neck cancer. Improvement in tumor-free intervals and cure rates of patients with cancer of the head and neck will almost certainly come from utilization of more than one type of treatment in the same patient. For example, in treatment for formidable lesions this might take the form of a short course of preoperative chemotherapy followed by surgery. Postoperative chemotherapy might then be employed in preoperative responders, with the addition of radiation according to the usual postoperative indications. Specific or nonspecific immunotherapy might be used on a long-term basis, preoperatively and postoperatively. In selected patients, utilization of multiple modalities early in a careful long-term plan may bring improvement over current results from employment of adjuvant measures only after recurrence or metastatic spread is clinically obvious.


Alpha-fetoprotein and albumin in experimentally-induced exencephaly in the rat. Alpha-fetoprotein and albumin were quantified in the sera and amniotic fluids from control, Vitamin A-treated non-exencephalic and Vitamin A-treated exencephalic rat fetuses. Exencephaly was associated with amniotic fluid alpha-fetoprotein concentrations which were significantly elevated over those of Vitamin A-treated non-exencephalic and of untreated fetuses. Amniotic fluid albumin concentrations also were higher in the exencephalic fetuses than in the non-exencephalic fetuses. Serum alpha-fetoprotein and albumin concentrations were lower in the exencephalic than in the non-exencephalic fetuses. The results are cosistent with simple diffusion across a defective barrier as the cause of elevated amniotic fluid alpha-fetoprotein concentrations in the presence of open neural tube defects. This experimental model of neural tube defects result in changes in amniotic fluid alpha-fetoprotein similar to those changes found in human amniotic fluid alpha-fetoprotein concentrations in the presence of neural tube defects.


[Correlation of alpha-2 pregnancy associated glycoprotein with the clinical course of bronchial carcinoma (author's transl)]. Alpha-2 pregnancy associated glycoprotein is a high molecular, carbohydrate containing plasma protein with unknown biological function. During clinical treatment of 25 patients with bronchial carcinoma alpha-2 PAG was measured by the electroimmuno-diffusion method according to Laurell. A good correlation was observed between alpha-2 PAG serum levels and the course of the disease in 21 patients. Patients whose course of disease could not be influenced therapeutically showed continously increasing levels of alpha-2 PAG; patients who responded to therapy, showed a significant decrease in alpha-2 PAG serum levels. These findings indicate that periodic determinations of serum alpha-2 PAG may be helpful for controlling the course of bronchial carcinoma.


Preliminary characterization of isoimmunogenic placental antigens in the rabbit. By isoimmunization of adult virgin female rabbits with rabbit placental extracts we have demonstrated the production of humoral antibody against two antigens, Ag-1 and Ag-2. Neither antigen is a normal serum protein, nor are they allotype proteins. Ag-1 has an alpha-2 mobility and a molecular weights of about 400,000. Ag-2 exhibits a gamma mobility but was not characterized. The antibody activity directed to Ag-1 in immune sera was the complement-fixing IgG fraction. Direct fluorescence-labeled antibody technique revealed that Ag-1 is a ubiquitous intracellular antigen primarily localized in the nucleus. The fast-growing, SV-40 virus-transformed rabbit kidney cell line (TRK-1) expressed much higher levels of Ag-1 than the slow-growing, non-transformed normal rabbit kidney cell line (LLC-RK1). The possibility that elevation of Ag-1 production is associated with rapid cell proliferation is discussed.


Stimulation of T lymphocytes by autologous non-T lymphoid cells. Participation of HLA-D? Non-T lymphoid cells were found to be able to stimulate autologous T cells in vitro. This "autologous" response was shown to be about 20% of the response to allogeneic unfractionated lymphocytes. The ability to induce autostimulation appeared to be a property of the Ig-positive lymphocyte fraction. Blocking experiments with allosera recognizing HLA-D-associated determinants suggested that the HLA-D determinants present on the stimulating cells might be involved in the stimulation of autologous T cells.


An examination of HLA frequencies in three age groups. The question as to whether the distribution of HLA antigens differs between old and young persons has been studied only in a few population groups. There are observations showing an increase of heterozygosity of the HLA system (Bender et al. 1973, Gerkins et al. 1974) which indicate an advantage of heterozygosity for survival, but other studies fail to confirm this finding )Albert et al. 1974, Mucurová et al. 1975, Bender et al. 1976). Since the present authors, in a study of HLA gene frequencies on five small Danish islands (Hansen et al. 1974) had found a tendency to a changed frequency of certain HLA types among the oldest persons, it was decided to examine this question by typing larger numbers of persons of different age groups.


Frozen-thawed mononuclear cells as a source of B lymphocytes for antibody screening. B lymphocytes were isolated from fresh blood and frozen-thawed lymphocyte preparations from the same donors. A panel of 55 human antisera, previously found to react with human peripheral blood B lymphocytes in cytotoxicity assays, was screened against these B-cell preparations. There was essentially no difference in the reactions of B-cell antisera with fresh B lymphocytes when compared with frozen-thawed cells. The percentage recovery of B cells from the fresh and frozen preparations was not significantly different.


HLA antigens and myxedema.

HLA antigens and myxedema. In 22 cases of myxedema 22 HLA-A and B antigens were typed. In six out of eight patients with a history of subacute thyroiditis Bw35 antigen was demonstrated, while in none of 14 patients free from this disease in anamnesis could this antigen be found. This difference is statistically significant, and suggests classifying of myxedema patients into two groups according to pathogenesis of the disease.


HLA antigens in essential hypertension. Relation to familiar disposition and serum immunoglobulins. HLA-typing was performed in 149 patients with essential hypertension, 86 males and 63 females. In 66 patients with significantly elevated serum levels of immunoglobulins, HLA-B27 was increased to 18%, from 8% in the controls (P less than 0.007). This was not significant when correcting the P-value for the number of antigens analyzed, but confirms reports of an association of this antigen with serum levels of immunoglobulins. HLA-Bw15 was found to be increased two-fold in patients with a family history of hypertension (P corrected less than 0.05) and in patients with autoantibodies (not significant). This is discussed in relation to the increase of Bw15 in juvenile diabetes and in Systemic Lupus Erythematosus, diseases in which vascular damage also occurs.


Soluble HLA antigens present in normal human serum. HLA antigens have been detected in normal human serum by inhibition of monospecific HLA antisera in the complement-dependent cytotoxicity test. The antigens present in serum were the same as those found on the donor's lymphocytes. HLA-A9 was unique in that it was present in serum at inhibitory titers of 1:8 to 1:32 whereas the majority of A-and B-locus antigens were present at titers of 1:4 or less. Serum HLA-A9 antigens were found in the high density lipoprotein fraction with a molecular weight greater than 200,000. In the presence of detergent they have an apparent molecular weight of 86,000 which is reduced to 46,000 when treated with papain. These values are similar to those obtained for detergent-solubilized cellular HLA antigens.


HLA-D typing by homozygous typing cells. A statistical analysis of experimental and biological variation. Several normalization procedures have been applied to single MLC-typing experiments in order to neutralize experimental variation and hence to secure assignment of HLA-D phenotypes. The present paper concerns a statistical description and isolation of experimental and biological factors in repeated MLC-typing experiments. The statistical model used gives a meaningful description of the variables in MLC as judged by its application to MLC-typing data of HLA-identical siblings. Subsequent testing of the model in an HLA-A, -B,-C and -D-genotyped family material provides evidence that the level of typing response to selected homozygous typing cells may be influenced by factors coded for by the homologous HLA-D region. It is, however, concluded that such evidence must be accepted with caution due to the (for the present statistical purpose) suboptimal design for the HLA-D typing experiments and hence the relative insensitivity of the method. A general method for locating erroneous triplicates is devised.


Association between HLA determinants and complement receptors on human lymphocytes. The relationship between the major histocompatibility complex (MHC) and functional receptors on the surface of human lymphocytes was studied. HLA antisera were tested for their effect on the formation of E-, EA-, and EAC'-rosettes by human peripheral blood lymphocytes (PBL). Antisera to various HLA specificities inhibited the formation of EAC'-rosettes, but had no effect on the formation of E-rosettes. The formation of EA-rosettes was inhibited by HLA antisera only in part among the individuals tested. Anti beta2-microglobulin serum resembled HLA antisera in its effect on the formation of the various rosettes. HLA determinants and complement receptors are different entities on the cell surface since elimination of complement receptors by trypsin treatment does not seem to affect the expression of HLA antigens on the cell surface. It is suggested that EAC' receptors are located close to HLA determinants.


Localization of reducing group activity in the structural protein ribbons of the egg capsule of the gastropod mollusc Buccinum undatum L. Egg capsules of the gastropod molluse Buccinum undatum L. show a staining reaction with silver-methenamine reagent with prior treatment with periodate. The reactivity is specifically localized on the striated structural protein ribbons which form the capsule walls. The staining is in the region of ribbon most resistant to chemical degradation and where the constituent protein monomers are believed to overlap and be cross-linked. Since the proteins contain little cysteine it is likely that the staining originates in aldehyde groups. Staining is abolished by borohydride reduction. It is suggested that the aldehyde groups are a locus of stabilization and cross-linking since previous work has also shown association of an aldehyde secretion with hardening of the capsules.


[Combination therapy by bleomycin, methotrexate, and telecobalt irradiation in carcinoma of the oral cavity (author's transl)]. 20 patients with advanced carcinomas of the oral cavity (T3NxMo) were treated at the same time with the cytostatic drugs bleomycin and methotrexate as well as with a cobalt-60-irradiation. 14 of them are tumor free after an observation period of one half to two and a half years. Among them were 4 recurrences that had to be treated surgically. 1 patient is living with a residual tumor which cannot be further treated. 5 patients died of the tumor or of other causes. The survival rate, which is 80% after 1 year, is, as a tentative result, higher than could be attained by other therapeutic measures.


[Radium treatment of primary vaginal carcinoma (author's transl)]. Between 1951 and 1970, 263 cases with primary carcinoma of the vagina were observed at the Irradiation-Department of the Ist University Clinic of Obstetrics and Gynecology in Vienna. As method of choice the individual, fractioned and protracted Radium-Röntgen-Telekoalt-therapy is recommended. Of the 263 primary vaginal carcinomas 112 (42,5%) were cured. During the time mentioned in this report, we did not have any primary mortality; 24 women, however, could only be subjected to a palliative therapy, 20 patients died from an intercurrent disease and 20 women succumbed to a second carcinoma. Conclusively, the authors present a survey about the results in vaginal carcinoma.


Single dose palliative irradiation for bony metastasis. 315 patients with bony metastasis were given palliative radiation therapy for the control of pain; 69 of these patients received single high dose treatment and the remaining patients were treated by daily fractionation. No difference in the pain relief was observed in either method of irradiation. Morbidity was slightly more with single dose therapy, but was well tolerated. Rapid relief of pain, avoidance of exhausting and painful journey for daily treatment and saving of machine time in the busy radiotherapy department make single dose therapy a preferable modality in the management of bony metastasis.


Antibody response to horse gamma-globulin in recipients of renal allografts: relationship with transplant crises and transplant survival. Anti-antilymphocyte globulin (ALG) antibody response was measured every day during and after ALG treatment in 52 recipients of renal allografts. IgM antibodies became detectable in 37 patients, usually at day 8 and IgG antibodies appeared 3 days after the IgM in 21 of 37 cases. Of 30 transplant crises recorded between days 6 and 11, 20 coincided with the onset of the antibody response, and the incidence of crises during this period was higher among antibody producers than among nonproducers. In 31 patients a partial or total unresponsiveness to ALG could be achieved. Transplant survival at 3 months was better in this group than among good responders (P less than 0.01). Anti-ALG antibody response may then be usable as an early indication of individual differences in reactivity against transplant antigens.


[Cytochemical study of different stages in the life cycle of Toxoplasma gondii. I. Nucleic acids and proteins in endozoites]. Using the Feulgen technique in addition to the methyl green-pyronin and gallocyanin-chromalum staining, nucleic acids were detected in Toxoplasma gondii of strains SS-119 and RH DNA was revealed in the nuclei of both intracellular and free individuals examined on various days (2--6) after mouse inoculation. A high RNA content in the cytoplasm of endozoites is a most characteristic feature of this stage. However, no definite nucleolus has been demonstrated in the endozoite nucleus. Using the Fast green and Alcian blue techniques, resp., histones were detected in the endozoite nuclei whose locality corresponded to that of Feulgen-positive material. The Acrolein-Schiff method located aldehyde groups of protein in endozoites, the detected stuff being confined mainly to the nuclear and perinuclear areas of the parasite. Tannofilic protein seems to screen the endozoite body, no difference between nuclear and cytoplasmic staining being seen. Tryptophan and tyrosin were not detected in the endozoites of Toxoplasma. The results obtained on Toxoplasma endozoites are compared with the metabolic patterns seen in the host cells of the peritoneal exudate and with previous literature data.


[Radioimmunologic serum determinations of alpha-fetoprotein in patients with tumors of the testis (author's transl)]. Alpha-fetoprotein (AEP) serum levels were determined by a new radioimmunoassay (sensitivity about 5 ng/ml) in 47 patients with teratocarcinoma of the testis and in 58 cases with seminoma before operation and during the postoperative course of the disease. In 140 healthy adult persons normal AFP levels below 15 ng/ml were measured. Of 14 preoperative cases with teratocarcinoma, 12 (86%) showed pathologic AFP levels over 20 ng/ml up to 3875 ng/ml. Postoperatively, cases free of metastases developed normal AFP concentrations within 4 to 10 weeks, whereas cases with distant metastases retained constant or increasing pathologic levels following a clinical deterioration. Only in three postoperative cases were Ouchterlony-positive results (AFP sensitivity about 10 000 ng/ml) observed. In contrast, patients with seminoma showed normal AFP levels below 20 ng/ml pre- and postoperatively. According to the results, AFP radioimmunoassay is recommended as an important tool for the differentiation of teratocarcinoma from other tumors of the testis and as a useful parameter for the control of therapy and the course of the disease.


Cochlear vascular changes in streptozotocin diabetes in chinchillas. Chinchillas were made diabetic by streptozotocin intraperitoneal injection, and the cochlear blood vessels were studied using surface preparation techniques after 3, 6, and 12 months of established diabetes. The following findings were reported: (1) a decrease of alkaline phosphatase activity in the walls of cochlear capillaries after six months of established diabetes, (2) a generalized involvement of the cochlear microcirculation as evidenced by the decrease in alkaline phosphatase activity and by narrowing and irregularities of the capillary lumen, and (3) areas of complete capillary closure in the stria vascularis of the basal turn after 6 and 12 months of established diabetes.


Distribution of IgG subclasses in commercial and some experimental gamma-globulin preparations. The IgG subclass distribution was determined in six commercial and in four experimental human gamma-globulin preparations. The concentrations of IgG subclasses were measured in a modified radiommunoassay using subclass-specific antisera. In commercial gamma-globulins, the distribution of the subclasses corresponded roughly to the distribution in normal human serum. A considerable enrichment of the IgG 4 was found in experimental lots prepared either from the ethanol fraction III or from the rivanol-precipitable IgG.


Comparison of low-molecular-weight products following reaction of C3-C3b with C3b inactivator and with trypsin. Substitution of trypsin for Konglutinogen-activating factor (KAF) in the procedure for cleaving C3d from C3-C3b substrate produced a relatively heterogeneous low-molecular-weight fraction (C3d-Tryp) which differed in a number of ways from the KAF-mediated cleavage product (C3d-KAF). The differences were demonstrable by agar and polyacrylamide gel electrophoresis, 125I-labelling, content of immunoreactive 125I-labelled C3d, inhibition of anti-complement antiglobulin reagents and rabbit immunization. By comparison with C3d-KAF, the C3d in C3d-Tryp was more heterogeneous and exhibited a faster electrophoretic mobility in agar at pH 8.6. By contrast to C3d-KAF, C3d-Tryp contained protein carrying C3c antigenic determinants.


[Clinical morphological and immunological characteristics of lupus nephropathy]. Analysis is carried out of the clinical, pathomorphological and immunological characteristic of lupus nephropathy in 62 patients, 56 females and 6 males. A series of new investigation methods were used for that purpose. An early tendency towards kidney involvement in the course of LED is established and in 22 of the patients (36%) the renal symptoms have been the first clinical manifestations of the basic illness. Lupus nephropathy progresses most often with a nephrosis syndrome (in 66.1% of the patients), rarely pure and not combined with hypertension and/or with renal insufficiency. The pathomorphological changes are rather multiform but in the majority of the cases almost all structural elements of glomerules and the rest of the renal tissue are affected. The clinical picture severity, histopathological changes and nephropathy evolution course were established to be distinctly dependent on the course acuteness of the basic morbid process. The importance of the detailed study of the clinico-morphological and immune characteristic of lupus nephropathy upon the timely diagnosis. Proper treatment and the prognosis assessment of the illness is stressed upon.


[Clinical observations on the use of high-dose methotrexate treatment in osteogenic sarcoma (author's transl)]. Since January 1976 high-dose methotrexate (HDMTX) therapy has been used in the management of patients with osteogenic sarcoma at the Orthopaedic Department, University of Vienna. 7500 mg MTX/sqm body surface is administrated in a four-hour infusion with citrovorum factor rescue. This therapy is combined with dactinomycin, adriamycin, bleomycin, cyclophosphamide and vincristine in a multi-drug chemotherapeutic program as a prophylactic regimen after surgical treatment of the primary tumour, as well as in the management of metastases. So far, 12 patients have received a total of 46 infusions with HDMTX at montly intervals (6 patients already had widespread metastases). The use of several precautions such as adequate hydration 3 l/sqm body surface fluid), systematic alkalinization of the urine and regular control of the serum MTX level renders HDMTX therapy less hazardous. Five out of the 46 infusions were followed by mild toxic reactions consisting of mouth ulceration, fever and/or bone marrow depression. One out of the 6 patients with metastases and 5 out of the 6 patients receiving HDMTX as a prophylactic measure are without evidence of disease at present. In view of the short observation period, this report is limited to clinical observations only.


Chemotherapy studies in autochthonous rat tumors. Forestomach and bladder cancer. Acetoxymethyl-methyl-nitrosamine (AMMN) induced only carcinomas of the forestomach in female Sprague-Dawley rats after an induction time of about 100 days when applied orally twice weekly in single doses (d) of 3.5 mg/kg body weight, Butyl-butanol-nitrosamine (BBN) selectively produced bladder tumors in female Sprague-Dawley rats after about 280 days when given in daily oral single doses (d) of 10 mg/kg body weight. The reactions of a total of 520 rats with chemically induced tumors were tested using 4-drug combination chemotherapy with different equitoxic doses of Adriamycin (Adm), Methotrexate (Mtx), 5-Fluorouracil (5-FU) and Bleomycin (Blm). The influences of combined therapy on mean sruvival time, tumor weight, histology of tumors, and adverse side effects of therapy are herein described. The results showed to be tumorspecific. In addition, the comparability of experimental chemotherapy in autochthonous rat tumors to clinical experience is discussed.


[Specificity of the human "leukocytic virus of leukemia"]. The evidence has been obtained indicating the presence of the antigen of leukocyte leukosis virus (LLV) in specimens from patients with leukosis. Immunofluorescence tests with rabbit immune serum to LLV revealed specific fluorescence of the cytoplasm of cells in 19 out of 32 bone marrow punctates and leukocytes in 10 out of 12 blood smears from patients with acute leukosis and chronic myeloleukosis. In these tests, the difference from analogous control materials (from donors, patients with polyarthritis, reticulosclerodermia, mveloma, etc. is highly statistically significant. By the CFT, antibody to LLV-infected cells were detected in 60.8% of patients with leukosis and 18.5% of donors. When examined by the gel precipitation test with the appropriate test-systems LLV antigen was found to contain no group-specific antigen of murine leukosis virus or antigen of oncornaviris D from HEp-2 continuous cell line.


[Determination of the pregnancy associated alpha-2-glycoprotein (PAG) in pregnant women with reference to the number of previous pregnancies]. By estimation of PAG level from 33 primipara, 20 second-para and 11 third-para it was investigated if there are a correlation between PAG concentration and the number of gravidity or the weight of newborn respectively. The PAG concentration was estimated by so called Laurell electrophoresis and expressed in mm precipitate column. The middle concentration of PAG disclose in primipara 24,7, in second-para 23,0 and in third-para 21,1 mm. The average weight of newborn was to found a contrary tendency. The difference of PAG level between primi- and third-para was statistically significant.


[Prenatal diagnosis of genetic defects from the amniotic fluid. Report of experiences]. 42 pregnancies were monitored by transabdominal amniocentesis followed by karyotyping. Biochemical assays of cultured amniotic fluid cells, 50 analysis of alpha1-fetoprotein and estimations of the number of y-bodies in the amniotic fluid cells was also made. One chromosomal aberration (47, XY, + 18) was found in 13 pregnancies tested because of advanced maternal age. In 6 pregnancies with a recurrence risk of Down's Syndrom, one fetus with abnormal karyotype (46, XY, 5p-) was detected.


[On the similarity of antigen between torulopsis and salmonella (author's transl)]. The immune sera for Torulopsis apicola, T. bovine, T. colliculosa, T. fructus, T. glabrata, T. haemulonii and T. kestoni agglutinated Salmonella cholerae-suis (6,7). The immune serum for S. cholerae-suis agglutinated Torulopsis apicola, T. bovina, T. colliculosa, T. fructus, T. glabrata, T. haemulonii and T. kestoni. Absorption and agglutination cross test demonstrated common antigen factors in the tested Torulopsis species and in S. cholerae-suis (6,7).


[Global program of smallpox eradication. 1. Smallpox in the world before acceptance of the program of its eradication by the World Health Organization]. Despite a considerable success in control smallpox in a number of countries reached as a result of vaccination the problem of eradication of this infection could not be solved without uniting the efforts of all the countries in the world. Guided by humanity principles the delegation of the USSR suggested in 1958 a program of smallpox eradication in the whole world. World smallpox morbidity is analyzed in this work.


[Sensitization to mites in house dust among children suffering bronchial asthma]. The results of studying allergy to domestic dust in 168 patients suffering from bronchial asthma are presented. The diagnosis was made by means of the domestic dust allergen (10000 PNU), fraction E extracted from the whole allergen by Berrens and Young's method, and with lyophilized extract from D. pteronussinus, farinae and Glycyphagus ticks isolated from domestic dust by Voohorst and Spieksma's method. In parallel, IgE was determined in the blood serum of the patients under study by the radio-allergo-sorbent test; IgG was also determined. Microticks proved to be not the only factor determining the activity of domestic dust. Results of diagnosis in vivo and in vitro were found to correlate. The authors believe that the activity of domestic dust allergen formed on account of the reactions of the Maillard's type, in which a significant role was played by the "lysine-sugar) compounds.


[Immunoglobulin FAB-fragments: specific activity and reactogenicity. III. Comparative study of the antigenic properties of anti-encephalitic gamma-globulin and FAB-fragments isolated from it]. Parenteral administration of antiencephalytic gamma-globulin and of the Fab-fragments, extracted from it, to rabbits stimulated the formation of specific antibodies. The maximal blood serum specific antibody level in rabbits reimmunized with Fab-fragments was much lower than that following the reimmunization of rabbits with gamma-globulin. Antibodies specific to gamma-globulin and Fab-fragments were concentrated in the gamma-globulin fraction of the immune sera and could be referred to the immunoglobulins of G class.


[Immunogenicity of isocomponents of the alpha-toxoid of Cl. oedematiens for mice of opposite reacting genotypes]. There was revealed molecular heterogeneity of the highly purified Cl. oedematiens alpha-toxoid. By the method of isoelectrical focussing alpha-toxoid was divided into isocomponents with the isoelectrical points of 5.33 +/- 0.02 and 4.91 +/- 0.08 with an equal specific activity and serological specificity. In studying the immunogenicity of alpha-toxoid and its isocomponents in experiments on mice of oppositely reacting genotypes it was shown that for mice of the low reacting strain (DBA/2) the the alpha-toxoid isocomponents possessed a much greater immunogenicity than the highly purified alpha-toxoid; under the same conditions the immunogenicity of the alpha-toxoid isocomponents for mice of the highly reacting strain (CBA) failed to differ from the immunogenicity of the highly purified alpha-toxoid.


[Immunologic study of R-mutants of S. minnesota and water-soluble antigens of S. typhimurium]. Protective properties of Ra- and Re-chemotypes of S. minnesota were studied in experiments on active and passive protection of albino mice from infection with a virulent S. typhimurium culture. Vaccines prepared from the Ra- and Re-mutants of S. minnesota were administered to the animals in the sum total dose of from 0.05 to 0.6 mg. Hyperimmune and normal rabbit sera were administered in doses of 0.3 and 0.5 ml. S. mineesota Ra- and Re-mutants in the doses tested proved to possess a weak protective activity: the level of the immunized mice nonspecific protection from the experimental salmonellosis failed to exceed the natural resistance level. Immunogenicity of Ra-mutant was markedly greater than the immunogenicity of Re-mutant. A marked protective activity against the experimental salmonellosis in mice was possessed by the antigenic complexes from the homologous strain only.


[Clinical picture and pathogenesis of the Refsum syndrome]. The author reports of 2 cases (sisters of 13 and 15 years old) with the Refsum syndrome. The disease had its onset at the age of 12 and 5 years with a progressive development and remissions. The clinical picture was characterized by a recurrent syndrome of polyradiculoneurites with a slight protein cellular dissociation in the CSF, an expressed sensitive ataxia with elements of cerebellar disorders, a drop in the acuity of sight, audition, intellectual level and a deformation of the talipes of the Friedreich type. In a single examination of fatty acids in the blood serum by the method of gas chromotography there were no data pointing to the existence of 3, 7, 11, 15-tetra metylhexadecone acids. On the basis of an immunological study the author discusses the role of autoimmune reactions in the pathogenesis of the diseases. A differential diagnosis was conducted between acanthocytosis and porphyria with recommendations in regard to treatment.


Neonatal sebaceous glands: fine structure of sebaceous and dendritic cells. Ultrastructural features of sebaceous glands in newborns were examined in adnexal polyp lesions of neonatal skin. Material for electron microscopy was obtained from the nipple areola of 10 Japanese newborn babies of both sexes, less than 8 days of age. The cell organization of the neonatal sebaceous acini consisted of undifferentiated, differentiating, and mature sebaceous cells, and the sequence of sebaceous transformation seemed to be consistent with that described in the postnatal acini. The sheet of continuous basal lamina covering the sebaceous acini was neither distorted nor convoluted. This configuration in the basal lamina revealed no convincing evidence for physiological involution of the neonatal sebaceous cells were identified at the outer periphery of the sebaceous glnads. Melanocytes in symbiosis with the sebaceous acini in concurrent presence of Langerhans cells.


New staining techniques for the Langerhans cell. Three new techniques are described for staining the Langerhans cell in whole mounts of fresh human and guinea pig epidermis. These employ paraphenylenediamine, gold sodium thiomalate and cobalt chloride, respectively, and require appropriate epidermal separation with EDTA, ammonium thiocyanate or sodium bromide. Used in conjunction with a modified adenosine triphosphatase stain, these techniques provide greater capability for observing the Langerhans cell in disease states than can be achieved by any single stain. A combined stain with adenosine triphosphate and gold is also described.


A possible dysfunction of melanosome transfer in leprosy: an electron-microscopic study. An E.M.  study was carried out to investigate whether Mycobacterium leprae occur intracellularly in epidermal melanocytes. As this could not be confirmed, the selective killing of melanocytes by cytotoxic lymphocytes could not explain the hypopigmentation in types of leprosy with a relative good immune response. There were indications that these hypopigmented lesions resulted from a disturbed transfer of melanosomes from melanocytes to keratinocytes. Further research is in progress.


Metabolism of 5-S-cyteinyldopa by O-methylation. 5-S-cysteinyldopa is metabolized by O-methylation on incubation with a liver extract and S-adenosyl methionine. O-methylated 5-S-cysteinyldopa isolated from melanoma urines by ion exchange and paper chromatography was identified by gas chromatography-mass spectrometry and NMR.


Intracellular distribution of dopa and 5-S-cysteinyldopa in Harding-Passey melanoma. The concentrations of dopa and 5-S-cysteinyldopa were determined in the various cell fractions of Harding-Passey melanomas. Dopa was present in larger amounts than was 5-S-cysteinyldopa in all cell fractions, but the dopa/5-S-cysteinyldopa ratio was lower in the soluble fraction and in the small-granule fraction than in the large-granule fraction. The soluble fraction contained the greatest amount of catechols. These findings are compatible with high tyrosinase activity not only in the melanosomes but also in the small-granule and soluble fractions.


An in vivo study of cell-mediated immunity in human warts. Preliminary results. Purified human papilloma virus (HPV) was used to study cell-mediated immunity (CMI) in patients with warts and in controls by means of the intradermal test (IDT). IDT was positive in 75% of patients with past history of warts, in 56% of patients presenting with warts, but in only 7% of controls. Immunofluorescent antibody levels were initially low and increased after injection of HPV antigen in all groups.


The significance of chromate ingestion in patients allergic to chromate. A double-blind study was carried out to demonstrate the significance of chromate ingestion in the persistence of chromic chromate dermatitis. Each of 31 chromate-allergic patients was given one tablet containing 7.1 mg potassium dichromate, plus a placebo tablet. The dermatitis of 11 of the 31 patients flared after the ingestion of chromate, but not after placebo. 3 patients had equivocal reactions to both tablets; the dermatitis worsened in 2 patients following ingestion of the placebo but not after the chromate tablet. No statistically significant difference could be found between reactivity to chromate and eczema of dyshidrotic morphology. Nor was it possible to correlate the degree of patch test reactivity to the reaction following chromate ingestion. It is concluded that a low-chromate diet is of value in the management of patients with chronic chromate dermatitis.


Phenothiazine phototoxicity: an experimental study on chlorpromazine and related tricyclic drugs. A large number of phenothiazines and chemically related tricyclic drugs have been studied with respect to their phototoxic potency. Two methods were used, an in vivo technique based on the inflammatory response of the mouse tail after systemic administration of the drug plus UVA irradiation, and an in vitro method based on growth inhibition of Candida albicans. Of 27 commercial tricyclic drugs tested in vivo, the most potent were chlorpromazine and two other chlorinated compounds, prochlorperazine and perphenazine. Tricyclic drugs lacking nitrogen, sulphur, or both in their ring system showed no activity. All compounds phototoxic in the mouse were so in the yeast test as well. Here, however, the thioxanthenes (lacking nitrogen) were also highly active.


Elevated serum immunoglobulin levels in polymorphous light eruptions. Elevated immunoglobulin levels were demonstrated in the sera of patients suffering from chronic polymorphous light eruptions. Compared with corresponding levels in a control population, the IgE levels were elevated very significantly, the IgM levels significantly, and the IgG levels almost significantly. Apart from the occurrence of a low grade positive Waaler-Rose test titre in 14% of the patients, serological abnormalities associated with so-called collagen diseases could not be demonstrated.


Deficient neutrophil function in a patient with chronic mucocutaneous candidiasis, thymoma and myasthenia gravis. The case of a 68-year-old man who suffered the onset of chronic mucocutaneous candidiasis, thymoma, myasthenia gravis and a reversible neutrophil dysfunction during adult life is reported. All tests for humoral and cellular immunity proved normal. Thymectomy and the administration of transfer factor had no effect on the skin disease. Long-term oral administration of 5-fluorocytosine almost cleared the skin lesions; the neutrophil defect disappeared.


Squamous cell carcinoma appearing in X-ray-treated mycosis fungoides. Two patients with mycosis fungoides developed a squamous cell carcinoma of the skin on the neck. Upon verification by routine biopsy testing of material taken from a suppurating infiltrate of the neck, both patients were treated intermittently with X-rays. Both had developed the squamous cell carcinoma on a sun-exposed area. Patient 1 had been treated with Grenz-ray irradiation totalling 10 kilovolt (kV) 4400 rad. and Dermopan step IV (50 kV) 5200 rad.; while patient 2 recieved altogether: Grenz-rays 4600 rad., Dermopan step IV 400 rad., and soft X-rays (150 kV) 800 r. The latency period was, respectively, 3 and 10 years.


Comparative treatment of psoriasis with UV-light, trioxsalen plus UV-light, and coal tar plus UV-light. Areas within psoriasis plaques have been treated with UV-light alone, trioxsalen plus UV-light, and coal tar (liquid carbonis detergens) plus UV-light, using the 313, 365 and 405 nm wavelength bands in various doses. With the 313 nm band, the same degree of healing was obtained with all three types of treatment. With the 365 nm band, no healing was achieved with UV-light alone, but healing did occur with UV-light when the skin was sensitized with trioxsalen. Coal tar itself has a certain healing effect on psoriasis but the effect is so markedly enhanced by light of the 365 nm band that the healing is comparable to that obtained with the 313 nm band. No healing was seen with light of the 405 nm band. The patients who were healed with the 313 nm band alone, also healed with trioxsalen or coal tar plus UV-light of the 365 nm band. With each method there is an individual optimal light dose of 1--2 MED that gives healing.


Photochemotherapy of psoriasis with relevance to 8-methoxypsoralen plasma level and low intensity irradiation. The 8-methoxypsoralen (8-MOP) plasma level was determined in 31 patients during treatment with PUVA (psoralen + UVA light). The UVA light source was of a low intensity type, giving only 2 mW/sec/cm2 and required an irradiation time of 30 minutes. The lesions of 19 patients healed completely. Following an oral dose regimen adjusted to the patient's weight, the 8-MOP values at 2 hours varied from 2 ng/ml to 167 ng/ml (mean 56 ng/ml). There was no clearcut relation between the 8-MOP plasma level and the clinical response but in 9 patients there was a prompt response to treatment when the dose of psoralen was increased by 10 mg. In 5 patients the 8-MOP plasma levels was determined hourly for the first 4 hours and showed a peak at 2 hours except in one patient with very low values who had a peak at 4 hours. The augmentation of pigmentation was measured by means of reflectometry on three univolved areas. Two peaks were observed--one during the first week and the other after 2--3 weeks of therapy.


Oral zinc sulphate therapy for acne vulgaris. A double-blind controlled clinical trial was performed to evaluate the effect of oral zinc sulphate, 0.6 g daily, on acne vulgaris. Twenty patients received zinc sulphate tablets and 19 were given placebo tablets. Thirteen of the zinc group and 12 of the placebo group received their medication throughout a 12-week period, while the remaining patients were treated for 4 or 8 weeks. In all patients the numbers or papular and pustular acne lesions on the face and the back were significantly reduced, while larger infiltrates remained practically unaltered during the trial, which was performed from March through May 1975. No statistically significant difference in the improvement of the groups was demonstrable. Pretreatment serum zinc values, which were normal in all patients, rose significantly in the zinc group as well as in the control group, but the increase in the former was significantly higher. The negative therapeutical results might be attributable to the limited number of patients or related to the zinc dosage. Furthermore, the results might have been influenced by the unexplained rise in serum zinc values in the control group. A possible weak beneficial effect of zinc might also have been camouflaged by the seasonal variation in the severity of acne which was noted in this study.


Dextran polymer particles (Debrisan) in the treatment of penile ulcers. Dextran polymer particles (dextranomer; Debrisan) was used in the treatment of 25 patients with non-venereal penile ulcers. In 14 cases the ulcers were caused by herpes infection, 3 patients had dequalinum-induced necrosis and in 8 cases the etiology of the ulceration was unknown. The ulcers healed in most cases during the first week of treatment, and in all cases within 4 weeks. An almost immediate relief of pain was reported by most of the patients.


Chronic dental fistule on the nose.

Chronic dental fistule on the nose. A case of chronic dental draining sinus on the dorsum of the nose is reported. The skin lesion, clinically simulating basal cell epithelioma, healed promptly after extraction and eradication of the periapical abscess of the right upper canine. The importance of considering this condition is emphasized in cases of chronic facial granulomatous or ulcerative lesions.


Systemic sarcoidosis with necrobiosis lipoidica-like scalp lesions. A 78-year-old woman is described, having systemic sarcoidosis for 15 years, involving the lungs, lymph nodes and the skin. Over the last 6 years she developed a progressive cicatricial alopecia with histologic changes of the granulomatous type of necrobiosis lipoidica surrounded by sarcoid granulomas.


Tranexamic acid (Cyklokapron) in chronic urticaria: a double-blind study. A double-blind study with tranexamic acid (Cyklokapron) was carried out in 17 patients with chronic urticaria. All patients had slightly depressed C1-chronic esterase inhibitor value. No significant differences were found between TA and placebo treatment periods.


Treatment of alopecia areata with DNCB--an immunostimulation? Ten patients with long-standing areate type alopecia totalis were sensitized with 1-chloro, 2, 4-dinitrobenzene (DNCB). Following sensitization they were painted once weekly on a 40 X 20 mm area of the vertex with DNCB in acetone, in concentrations adjusted to the allergic response. After 7 weeks, growth of hair was seen in the painted area in 3 patients and after 8 weeks all over the scalp in 3 other patients.


Multiple myeloma associated with Kaposi sarcoma. A patient with multiple myeloma (MM) who developed Kaposi sarcoma (KS) is described. The KS appeared 18 months after the diagnosis of MM and 1 month after the treatment was changed from cyclophosphamide to melphalan. The treatment with melphalan was discontinued and the spread of the KS was arrested by irradiation and bleomycin. One month after the melphalan was restarted, the KS advanced. The patient died 28 months after the diagnosis of MM and 10 months after KS had developed. The association of KS and MM is discussed and the previously reported cases are reviewed. A possible connection between the treatment with melphalan and the development of KS is proposed.


Non-specificity of crystal violet staining for renin granules. This study deals with the histochemical specificity of crystal violet staining. Histological dyes such as crystal violet (CI 42555), ethyl violet (CI 42600) and methyl violet (CI 42535) are regularly employed for the assessment of juxtaglomerular granulation (WILSON 1952; FRIEDBERG and REID 1966; MARIUZZI and NENCI 1966). WILSON's modification of BOWIE's procedure is the staining method most frequently used for demonstration of 'renin granules' in the juxtaglomerular cells (JC). It has been assumed that JC granularity parallels renin-induced hypertension (PITTS 1968).


Reversibility of lipofuscin accumulation caused by protein malnutrition in the motor cortex of squirrel monkeys, Saimiri scireus. Lipofuscin pigment has been demonstrated histochemically in the motor cortex by the use of several histochemical and cytochemical methods in the healthy (maintained on a diet with 25% protein content) and protein malnourished (maintained on a diet with 2% protein content) adult animals. 4 animals in the latter category were rehabilitated over a period of 11 months and various histochemical techniques were repeated on the motor cortex of these animals. The healthy animals showed a somewhat uniform distribution of lipofuscin pigment in the neuronal perikarya with the perineuronal glia showing only slight occurrence of pigment bodies. The malnourished animals exhibited a significantly larger number of lipofuscin bodies in the neuronal as well as glial perikarya. The neurons, especially, showed aggregations of lipofuscin bodies characterized by a large increase in the activity of acid phosphatase and simple esterases. The rehabilitated animals, however, showed a decrease of lipofuscin pigment in the neuronal perikarya with a concomitant loss of lysosomal enzymes, while a significant increase of these bodies was observed in the perineuronal glial cells. It is evident that the formation of lipofuscin pigment gets accelerated under the extrinsic influence of dietary protein deprivation in the adult animals, but the process is reversed at least to some extent by halting the dietary deficiency or its correction by rehabilitation. The perineuronal glial cells appear to play a significant role in the removal of lipofuscin bodies from the neuronal perikarya. The significance of these observations has been discussed.


Spectral characteristics of metachromatically stained cartilage: effects of enzymatic degradation and dehydration. When a microspectrophotometer was used to study cartilage, stained metachromatically with Azure A and Safranin O, the following 3 points were made: 1. the absorption maximum of stained cartilage matrix is identical to that reported for solutions of these dyes containing chondroitin sulfate; 2. partial enzymatic degradation of the cartilage matrix has no effect on the position of the absorption peak (although the intensity is greatly diminished); 3. ethanolic dehydration shifts the absorption peak somewhat toward the orthochromatic position, and decreases the intensity of the stain.


[Histochemical studies on the content of plasmin in the normal and hyperplastic prostate (author's transl)]. The content of plasmin is significantly reduced in the benign prostatic hypertrophy compared to the normal prostate. Histochemically plasmin is demonstrable by a combined incubation of substrate and inhibitor for plasmin. Plasmin is localized in the connective tissue and its function is to regulate the turnover of glycosaminoglycans. The fibrinolytic activity does not change significantly after prostatectomy because of the reduced content of plasmin in benign prostatic hypertrophy.


Characterization of extract of dog hair and dandruff from six different dog breeds by quantitative immunoelectrophoresis. Identification of allergens by crossed radioimmunoelectrophoresis (CRIE). An extract of mixed dog hair and dandruff from six different dog breeds (alsatian, boxer, collie, poodle, and long-haired and short-haired dachshund) was obtained by mild extraction, centrifugation, dialysis and freeze-drying. Extract of hair and dandruff from the individual dog breeds was obtained in the same way, but the material was not freeze-dried. Examination and characterization of the mixed extract by means of crossed immunoelectrophoresis revealed a precipitation pattern composed of 25 antigens, some of which were mutually partially identical, and a high content of dog serum proteins was found. Quantitative and qualitative differences between the individual dog breeds were demonstrated. Partial identity of the antigens of the mixed extract with antigens of serum, antigens of extracts of hair and dandruff from cat, cow, horse and guinea pig, and antigens from extract of house dust was also observed. By means of crossed radioimmunoelectrophoresis, using sera from 21 patients who were RAST-positive to dog hair and dandruff extract, the specific IgE-binding to antigens of the mixed extract was examined. On the basis of these results major and minor allergens were identified. Dog albumin was found to be a very important major allergen, but alpha1-antitrypsin and gamma-globulin were also identified. Furthermore, four non-serum proteins were shown to be allergens. No breed-specific allergens could be identified in the extracts from the individual dog breeds.


A simplified method for measuring basophil histamine release and blocking antibodies in hay fever patients. Basophil histamine content and cell preservation. A simplified method for measuring basophil histamine release in grass pollen hay fever patients has been developed. Leukocytes were challenged in vitro with extracts of Phleum pratense (timothy) and the release of histamine was determined indirectly as the residual histamine in the cell sediment. Several steps to purify histamine thus became superfluous and histamine was directly conjugated with o-phthaldialdehyde to form a fluorophore. The simplified method showed a basophil histamine content which was in accordance with results obtained by more specific methods. No difference in basophil histamine content was found between normal and allergic persons. For the histamine liberation assay blood could be adequately preserved for transport for 48 h at room temperature by adding cell culture medium. Basophil histamine release technique allows evaluation of cell sensitivity for determination of the degree of allergy as well as the level of blocking antibodies.


Cyclic AMP and allergic histamine release. Influence of methylxanthines on rat mast cells. Both isobutylmethylxanthine and theophylline increased the level of cyclic AMP in rat mast cells. Theophylline reduced the allergic histamine release, whereas isobutylmethylxanthine caused a pronounced potentiation of the histamine release. This indicates that the hypothesis of an inverse relationship between the level of cyclic AMP in mast cells and histamine release is inadequate.


Double-blind placebo-controlled clinical evaluation of oxatimide (R 35443). A novel potent anti-allergic drug in the treatment of hay fever. The efficacy of the new anti-allergic compound oxatimide was tested in a double-blind study against a placebo during the pollen season of 1976 in 215 patients (4 1/2--69 years) with hay fever. Adult patients were instructed to take two tablets (= 20 mg) three times a day for 2 weeks, children received one tablet/10 kg of body weight daily; in addition, they were given a supply of diphenhydramine as a potential supplement. Twelve patients, six from either group, were excluded from the analysis. A significantly higher proportion of patients from the active drug group (n = 104) experienced no or only a few days of complaints, i.e. rhinitis and conjunctivitis, as well as asthma-like complaints, as compared with those of the control group (n = 99). Also, diphenhydramine consumption became significantly lower in the active drug group from the second day onwards, whereas a gradual increase and continuous need were seen in the greater part of the control group. One week of treatment appears sufficient to judge whether the individual patient benefits from the drug or not.


The nature of dendritic cells of the epidermis of the white guinea pig. The melanocytes, the intermediate cells of Billingham and Medawar and the Langerhans' cells of the epidermis of the white guinea pig were found to be positive to Bielschowsky's silver and Gomori's acetylcholinesterase reactions. The melanocytes were full of Nissl substance. On these evidences, supported by other morphological and histochemical characteristics, the dendritic cells of the epidermis were considered to be nervous structures.


Distribution of epithelia and glands of the nasal septum mucosa in the rat. A histotopographic study of the nasal septum mucosa in rats was made using semi-serial sections stained with PAS-hematoxylin, reconstructed in form of maps representing the structure in a sagittal plane. The stratified squamous, respiratory and olfactory epithelia and Masera's organ cover 14.8, 43.6, 41.6 and 1.8%, respectively, of the septal surface (117.1 mm2). In the vestibular region, only ducts of PAS-negative glands of the respiratory region are found, and below the septum there is the infraseptal gland with PAS-negative acini. In the respiratory region, PAS-negative acinous glands form two groups: the superior and the inferior one occupying 10.5 and 1.5%, respectively, of the septal area. PAS-positive acinous glands are in the inferior half of the respiratory region and in a small anteroinferior portion of the olfactory region. Besides goblet cells broadly distributed, the respiratory epithelium presents scattered intraepithelial PAS-positive glands which are concentrated in the anterior portion and close to the nasopharyngeal duct. In the olfactory region prevail Bowman's PAS-positive glands which are also present in the mucosa of Masera's organ, but are not seen in the olfactory mucosa of Jacobson's organ. In the latter, PAS-positive glands are found in the respiratory mucosa. Globular leukocytes, cells of connective tissue origin, are constantly infiltrating the superior regions of the respiratory and olfactory epithelia, being more numerous in female rats.


[Rio Hortega's silver impregnation technic of paraffin sections. First report]. Rio Hortega's silver impregnation techniques were meant and developed for frozen sections. They offer real advantages even if they are employed for impregnation of paraffin sections. The authors have tried to transform these methods, and the results have been excellent. Further communications will follow to describe the transformation of other methods and variants.


Electron microscopic features of the resting microglia in the rabbit hippocampus, identified by silver carbonate staining. Vibratome sections of hippocampus of adult rabbits were stained by a modified Hortega's silver-carbonate method. Impregnated materials were examined by electron microscopy to decide fine-structural characteristics of the resting microglia. Comparing their characteristics with those of macrophages, we came to the following conclusions: (1) Impregnated resting microglia in the hippocampus of adult rabbits can be identified as cells having distinct fine structures. (2) Resting microglia are morphologically different from macrophages or their precursor cells, and, therefore, seem not to be hematogenous cells sojourning in the normal brain parenchyma.


Effects of zuclomiphene in combination with triparanol and ay-9944 on developing rat CNS morphology and biochemistry. Developing rats were injected intraperitoneally twice weekly with a combination of three hypocholesterolemic agents: Zuclomiphene (formerly called trans-clomiphene; dosage, 30 mg/kg body weight), Triparanol (30 mg/kg body weight) and AY-9944 (3 mg/kg body weight). Treatment was initiated at 4 days of age. Biochemical and electron microscopic examination was conducted on animals sacrificed at 20 days of age. Cytoplasmic inclusion bodies were not seen in the CNS. Isolated edematous changes were seen in myelinated axons. Analysis of the sterol content of the brain and spinal cords of drug-treated animals indicated the presence of abnormal concentrations of five sterols, desmosterol, 5alpha-cholesta-7,24-dien-3beta-ol, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). Zymosterol and 5alpha-cholesta 7,24-dien-3beta-ol were minor constituents (5--7% and 1--1.5% of total sterol, respectively). The 7-dehydrosterols represented approximately one-half (44--52%) of the total CNS sterol.


Combined staining of corneal endothelium by alizarine red and trypane blue. Combined staining by alizarine red and trypane blue is an easy and reliable method for in vitro visualization of corneal endothelial nuclei, cellular borders and uncovered parts of the membrane of Descemet. A stained full thickness wet mount can be prepared in less than five min. The staining method and preliminary findings concerning endothelial morphology in the centre and in the periphery of normal corneas are presented.


Nuclear DNA-content of parathyroid cells in adenomas, hyperplastic and normal glands. Nuclear DNA-content in parathyroid cell imprints from adenomas, hyperplastic and normal glands was determined. Two principally different staining procedures were applied: paratoseaniline-Feulgen and ethidium-bromide staining. All nuclei, particularly with the ethidium-bromide method were registered as containing even multiples of the normal human diploid DNA-content. Normal and hyperplastic glands showed greater than or equal to 98 per cent diploid nuclei, the remaining fraction was tetraploid. In adenomas the frequency of diploid nuclei varied from 50-98 per cent; the remaining were predominantly tetraploid, but octaploid and higher even ploidity also occurred. A good correlation was found between nuclear DNA-content and nuclear diameter. The findings indicate that determination of nuclear DNA-content of parathyroid cells may be a valuable contribution in the differentiation between hyperplasia and adenoma.


Differential staining of bacteria in clinical specimens using acridine orange buffered at low pH. Optimal conditions for acridine orange staining of air dried and methanol fixed bacteria on glass slides were studied. The pH of the staining buffer did not influence the fluorescence of an S. aureus and an E. coli strain at dye concentrations of 25-50 mg per litre. 81 bacterial strains representing 15 different species were stained with acridine orange under standard conditions, all strains showing orange fluorescence. The pH of the buffer influenced markedly the staining patterns of human cells and tissue materials, as represented by smears of peripheral blood, buccal scrapings, urethral secretions and tracheal exudates. The fluorescence obtained ranged from low intensity green at low pH values to bright orange at neutral and alkaline pH. This variability indicated a possibility of designing conditions for a differential staining method for the detection of bacteria in clinical specimens. The differential staining effect with a low pH in the buffer was confirmed on smears of buccal scrapings, cerebrospinal fluid samples and urethral secretions, showing orange fluorescence of the bacteria present and green-to-yellow fluorescence of background material, cells and tissue debris.


An in vitro assay for the quantitation of phagocytic cells of different anatomic origin. The survival of peritoneal exudate macrophages after 3 to 10 days in culture was examined by measuring the numbers of phagocytes per culture. This was determined by letting the cultured cells phagocytize Latex particles. The number of Latex particle-containing cells was taken as a measure of the survival of phagocytes. It was found that one tenth of the cells judged by light microscopy as macrophage-like survived the culture period. Thus, the calculated plating factor of 9.3 was used to estimate the actual number of macrophages in suspensions of spleen, lymph node or thymus cells by culturing these cells and subsequently counting Latex particle-containing cells. In addition, the acridine orange technique was used to determine actual numbers of macrophages in freshly prepared cell suspensions of lymphoid organs. Latex studies on spleen and thymus cells gave results correlating well with data obtained by the acridine orange technique. By contrast, many more acridine orange positive cells than phagocytizing cells were found when lymph node cells were cultured.


Glycogen in the cochlea during development. A recently developed technique for demonstrating glycogen by electron microscopy was used to study its location at various stages of cochlear development. It appears first in dispersed form in most of the cells of the otocyst at the stage of the 14-day rat embryo. Glycogen clums were found in Reissner's membrane at 17 days and in the future pillar cells shortly afterwards. Near the time of birth, glycogen appeared in the stria vascularis. By a few days after birth, heavy deposits were evident in the stria but glycogen had faded from the pillar cells and Reissner's membrane. Ten days after birth glycogen is no longer apparent in any of the cells of the cochlear duct except the outer hair cells.


The use of homocarnosine as a spacer in indirect haemagglutination. Homocarnosine (gamma-butyryl-L-histidine) was bound to erythrocytes through the action of glutaraldehyde in order to increase the number of available groups for diazotization on the surface of the cells. Diazotization was performed with tetrazotizized di-o-anisidine (TOD). TOD decomposed rapidly at an alkaline pH. The reagent was stabilized by the use of borate buffers. The presence of homocarnosine on erythrocytes enhanced the coupling of histidine by diazotization. TOD formed bonds of varying lability with alifatic amino and imino groups. This inhibited completely the formation of stable bonds with histidine and tyrosine. The relative amounts of stable bonds formed by TOD and human serum albumin and TOD and gamma-globulin varied inversely with the concentration of the proteins. The two proteins were used as model antigens and the presence of homocarnosine on the surface of the erythrocytes increased the sensitivity of the haemagglutination reaction by a factor of 4-8.


Pigmentation of the stria vascularis. The contribution of neural crest melanocytes. Because all stages of melanogenesis (premelanosome, melanosome and melanin granules) were found in intermediate cells of the rat stria vascularis, they can be classified as melanocytes. The marginal and basal cells of these rat specimens contained no pigment. Early in development, the melanocytes or future intermediate cells are located beneath the strial basal lamina. They penetrate this lamina to insert themselves between marginal cells. Both the melanocytes and marginal cells are believed to participate actively in the tissue rearrangements which ultimately bring the two cell types into intimate structural relationship. The ingrowing melanocytes and the mature, pigmented, intermediate cells which they form are frequently associated with blood vessels. Pretreatment with Dopa to enhance the melanin content of early melanocytes did not enable us to identify their route of migration into the stria.


The urinary sediment in hydronephrosis.

The urinary sediment in hydronephrosis. Phase contrast microscopy has been used for examination of urinary sediments from 19 patients with hydronephrosis. Casts were seldom seen. A raised number of erythrocytes was seen only in association with catheter, calculi or diabetes. A raised number of leukocytes was seen in patients with bacteriuria. A striking observation was the finding of a great proportion (64%) of histiocyte-like cells in six out of 12 cases in whom a differential count was performed. The proportion of histiocyte-like cells was small (14%) in cases with bacteriuria or history of urinary tract infection.


The clinical value of serum triiodothyronine, thyroxine and thyrotropin estimations during medical antithyroid treatment. The relation between clinical status and serial determinations of serum T3, serum T4 and serum TSH has been evaluated in the early phase of medical antithyroid treatment in 12 unselected hyperthyroid patients, and in 19 patients who later during treatment accidentally developed low serum T4 values. Determination of both serum T3 and serum T4 was found necessary to avoid undertreatment. Two patients with signs of hypothyroidism in the early phase developed low serum T4, while serum T3 and serum TSH remained normal. In all of the 19 patients selected with low serum T4, serum T3 was normal. Serum TSH was elevated in 5 patients without hypothroid symptoms, while 2 developed hypothyroid symptoms in spite of normal serum TSH values. Our results suggest that serum T4 is a more sensitive parameter than both serum TSH and serum T3 in avoiding overtreatment during medical antithyroid treatment.