H-2.28, an alloantigenic marker allelic to H-2.1, is expressed on all three known types of H-2 molecules. Each allele at the K or D region of the H-2 complex produces two kinds of "allelic" or mutually exclusive antigenic characteristics: its unique private specificity and a public specificity(ies) of either the H-2.28 or H-2.1 family. The private specificities of the K and D regions are expressed on H-2K and H-2D molecules, respectively. The D region produces another molecule, H-2L, which lacks the H-2K and H-2D private specificity but exhibits the H-2.28 or H-2.1 specificity. We analyzed the expression of the H-2.28 determinants on H-2K, H-2D, and H-2L molecules. When an antiserum against H-2.28 is used to sensitize cells where it can react with only H-2K molecules or H-2D molecules, by subsequent elution antibodies against H-2.28 are recovered that can also react with H-2L molecules. Hence, determinants reactive with antibodies against H-2.28 are present on H-2L as well as on H-2K and H-2D molecules. The expression of the H-2.28/H-2.1 polymorphism on all three known types of H-2 molecules, without some obvious relation to the private specificities, suggests that the antigenic determinants of these two kinds of allelic systems (private in contrast to H-2.28/H-2.1) may be controlled by separate genes, even when they are expressed on the same molecule.


Protection by zinc sulphate against reserpine-induced ulceration and other gastric effects in the rat. The effects of intraperitoneal pretreatment, 48 h beforehand, with zinc sulphate (22, 44 or 88 mg/kg) were studied on gastric ulceration, gastric secretion and changes in stomach wall mast cell counts induced after 4 h by reserpine (5 mg/kg) given intraperitoneally to intact (unoperated for pylorus occlusion) or pylorus-occluded rats. Zinc sulphate dose-dependently antagonised the gastric actions of reserpine by preventing ulceration in the ruminal and glandular segments of the stomach, reducing acid secretion, and inhibiting mast cell degranulation which occurred mainly in the glandular mucosal layer. The relationship between these findings and the action of zinc on gastric mast cell is discussed.


[Cerebellopontile angle symptomology in plasmocytoma: a case report]. The author reports on a patient with cerebellopontile angular symptomatology in the case of a plasmocytoma. The diagnosis of plasmocytoma was established from the pathological results of gamma globulin subfractionation and immune electrophoresis. Also commented in this discussion is the problem of essential cryptogenetic paraproteinosis.


Enhancement of anaphylactic mediator release from guinea-pig perfused lungs by fatty acid hydroperoxides. Fragments of chopped lung from indomethacin treated guinea-pigs had an anti-aggregating effect when added to human platelet rich plasma (PRP), probably due to the production of prostacyclin (PGI2) since the effect was inhibited by 15-hydroperoxy arachidonic acid (15-HPAA, 10 micrograms ml(-1)). Both 15-HPAA (1-20 micrograms ml(-1) min (-1)) and 13-hydroperoxy linoleic acid (13-HPLA, 20 micrograms ml(-1) min(-1)) caused a marked enhancement of the anaphylactic release of histamine, slow-reacting substance of anaphylaxis (SRS-A) and rabbit aorta contracting substance (RCS) from guinea-pig isolated perfused lungs. This enhancement was not reversed by the concomitant infusion of either PGI2 (5 micrograms ml(-1) min (-1)) or 6-oxo-prostaglandin F1alpha (6-oxo-PGF1alpha, 5 micrograms ml(-1) min(-1)). Anaphylactic release of histamine and SRS-A from guinea-pig perfused lungs was not inhibited by PGI2 (10 ng - 10 microgram ml(-1) min(-1)) but was inhibited by PGE2 (5 and 10 micrograms ml(-1) min (-1)). Antiserum raised to 5,6-dihydro prostacyclin (PGI1) in rabbits, which also binds PGI2, had no effect on the release of anaphylactic mediators. The fatty acid hydroperoxides may enhance mediator release either indirectly by augmenting thromboxane production or by a direct effect on sensitized cells. Further experiments to distinguish between these alternatives are described in the accompanying paper (27).


The mechanism of enhancement by fatty acid hydroperoxides of anaphylactic mediator release. Indomethacin augmented the release of histamine and SRS-A but abolished synthesis of TxB2. Compound CLI that inhibited both cyclo-oxygenase and lipoxygenase pathways of arachidonic acid metabolism did not augment release of anaphylactic mediators. 13-HPLA enhanced mediator release from lungs in which arachidonic acid metabolism was blocked by compount CLI. Thus, it is concluded that 13-HPLA enhances mediator release not by altering the balance of arachidonic acid metabolites, e.g. by inhibiting synthesis of prostacyclin, but by a direct effect on lung mast cells. A corollary to this conclusion is that the fatty acid hydroperoxide (HPETE) formed by lipoxygenase from arachidonic acid may also augment the release of anaphylactic mediators. Thus, the enhancement of mediator release by indomethacin may be attributed to increased synthesis of HPETE following inhibition of cyclo-oxygenase.


A review of the bleomycin experience in the United States. As bleomycin has up to now proved effective when used alone, the main thrust of current clinical investigations predominantly concerns its use in combination with other drugs. This has occurred along three broad patterns: 1) combination with vinca alkaloids which has been mainly in testicular carcinoma; 2) as part of multidrug regimens where bleomycin added for its lack of myelosuppression. This has occurred in the malignant lymphomas, lung cancer, and head and neck cancer; 3) in combination with radiotherapy which has taken place mostly in head and neck cervix cancer. To date, the combination of velban and bleomycin has had a major impact in improving the ability to induce complete remissions in advanced testicular carcinoma. Other drugs such as cis-platinum diaminedichloride and actinomycin D have been added and no definitive combination has been established. In the lymphomas the addition of bleomycin to the MOPP or CVP regimen has given higher complete response rates, but long-term survival data are still awaited.


Combined use of bleomycin with radiation in the treatment of cancer. 1. The data accumulated in this study up to the present time shows that combined treatment of radiation and bleomycin in intra-oral carcinoma resulted in marked tumor regression and a significantly higher tumor disappearance rate as compared with radiotherapy alone. The 18 month survival rate for the combined treatment group exceeded the rate for the control group by about 20%. 2. In esophagal carcinoma, bleomycin in combination with radiation markedly improved the regression rate of polypoid type tumor, while no significant improvement was observed in other types. The 18 month survival rate of the control group was about 10% higher than that of the combined treatment group. 3. In bronchogenic carcinoma, no significant difference was observed in tumor regression or survival rate of either group.


A sequential combination of bleomycin and mitomycin C in the treatment of advanced squamous cancers. The 49 patients with squamous cell type of cervical, lung, esophagus and head and neck cancers were treated with a sequential combination of bleomycin (BLM) and mitomycin C (MMC) as follows; 5 mg of BLM daily for 5 or 7 days followed by a single injection of 10 mg of MMC on day 6 or day 8. After one week of rest period, this course was repeated two to five times depending on the response or adverse effects. For cervical cancer, 17 patients out of 18 (94%) responded with complete remission (CR) in 13 (72%) and partial remission (PR) in 4 (22%). For lung cancer, four patients out of five responded. In two of the responders, metastatic tumors disappeared completely, but primary tumors decrease to about 10% in volume. For esophagal cancer, one patient out of 3 had CR after combining the BLM and MMC treatment with radiotherapy. For head and neck cancer, these were some differences in the response rates between two hospitals. In one hospital, 12 patients out of 22 (53%) responded, with CR in 4 (18%), whereas in the other hospital, 10 patients out of 11 (94%) responded, including eight with CR (72%). Regarding the toxicity, the overall incidence was very low, although lung complications were frequent. These results are promising with hopeful prospects for the control of advanced squamous cancers with metastasis.


Experimental results with the combination of bleomycin plus mitomycin C. This investigation has established the following: 1. Bleomycin, in combination with mitomycin C or other quinone-containing anticancer agents, stimulated the damage to KB cells in culture. 2. In AH66 tumor-bearing rats, the simultaneous treatments of bleomycin plus mitomycin C extend the lifespan. 3. The bleomycin-induced DNA chain breakage was enhanced by the NADPH-dependent microsomal electron transport system. The enhancement was also observed at the level of isolated nuclei and cells. Vitamin K2 and mitomycin C increased breakage at the cellular level by bleomycin and NADPH. 4. Bleomycin-Cu2+ had tendency to increase the lipid peroxidation reaction by the microsomes. However, the reaction was effectively inhibited by antioxidants. 5. Bleomycin induced aldehyde formation from DNA breakage. The formation was effectively inhibited by scavenging reactions with hydralazine hydrochloride or isoniazid. The possibility of suppressing the side effect of bleomycin was discussed in relation to TBA reactive compounds.


Clinical evaluation of new antitumor antibiotics. The clinical evaluation of new antibiotics and their analogs requires detailed analysis with respect to the best therapeutic strategy. In the case of anthracycline, diminished cardiac toxicity is as important an aim as increased activity. In the evaluation of cardiac toxicity the most important parameter must be the time to toxicity rather than the total dose. The new endomyocardial biopsy technique may be helpful in the study of analogs such as rubidazone, carminomycin and AD32. Actinomycin D analogs are also of interest, since this drug is part of several curative regimens, but its use has been limited by its severe acute toxicity. In the case of bleomycin, analogs with diminished pulmonary toxicity should be sought.


Antitumor antibiotic bioactivation, biotransformation and derivatization by microbial systems. Microbial transformations refer to reactions catalyzed by microbial enzymes, especially when specific and useful metabolites accumulate in fermentation media. These transformations have tremendous potential for use in the development of new antitumor drugs and these can also be used as models of mammalial metabolism. Microbial transformation experiments with antibiotics such as bleomycin, anthracyclines and with a variety of plant products are described.


[When a physician becomes the "disciple" of an undisciplined patient. Apropos of 8 cases of mandibular fracture]. The authors analyse the possibilities of avoiding active treatment of certin isolated fractures of the dentulous part of the mandible. They report 8 cases in which consolidation was obtained without problems, perfectly illustrating their analysis.


Studies on the pancreatic secretory trypsin inhibitor in plasma and its complex with trypsin in vivo and in vitro. Complexes between human or canine trypsin and the pancreatic secretory trypsin inhibitor (PSTI) from the same species were studied in vitro and in vivo. The following results were obtained. (1) Human or dog PSTI-trypsin complex without serum did not show any signs of dissociation after 3 h incubation at room temperature. (2) Immediate separation of reaction mixtures of human or canine serum and the corresponding PSTI-trypsin complexes by gel filtration showed that 60--70% of the trypsin was found in complex with alpha2-macroglobulin and the remainder in equal amounts in complex with alpha1-antitrypsin and PSTI, respectively. (3) The results of in vivo studies in dog indicated a similar rapid dissociation of the complexes in the circulation. (4) The elimination for intravenously administered 125I-labelled PSTI was rapid to about 20% of the initial value with a half-life of about 8 min for the initial part of the curve. No organ accumulation of the labelled inhibitor was found. (5) Most of the radioactivity injected was recovered in the urine bound to degradation products but part of it was bound to biologically active inhibitor.


Histochemical and radiologic studies of the human fetal mandibular condyle. Histochemical investigations on the mandibular condyle were performed on 72 human embryos and fetuses of crown-rump lengths (CRL) ranging from 26 to 186 mm, representing skeletal maturity indices expressed in CNO values (CNO = composite number of ossified bones in the hand and foot) ranging from 0-0 to 19-12. The development of the mandibular condyle is described according to morphology and to histochemical reactions for glycosaminoglucuronglycans, collagen, glycogen, alkaline and acid phosphatase, and nonspecific AS esterase. The development is described for (1) the bony component of the mandibular condyle, (2) the condylar cartilage, and (3) the fibrous cover of the mandibular condyle. For each tissue component, maturation steps are set up and included in the total evaluation of the condylar maturity stages. The developmental sequence set up on the basis of the morphologic and histochemical findings was followed by all condyles investigated. From this it may be presumed that the developmental sequence in human mandibular condylar components is constant during the former half of the prenatal period. The material available did not justify a description of skeletal development in the mandibular condyle as a function of fetal size, CRL, or skeletal maturity in the hand and foot.


Possible detection of HLA-DR alloantigenic specificities in man with unabsorbed rabbit antisera. Thirty-six rabbits were immunized with precipitin lines formed between detergent solubilized membrane fractions from HLA-D-homozygous cells and a rabbit antiserum to human B cells (anti-p 23/30). Thirty-one of the rabbits produced B-cell specific cytotoxic antibodies and twelve of the antibodies were also precipitating in gel diffusion. In cytotoxicity tests six of the antisera showed clear preferential reactivity with the immunizing HLA-D (DR) antigen. Thus immunization of rabbits might prove valuable for the production of HLA-DR typing reagents.


Islet-cell antibodies (ICA) in diabetes mellitus (evidence of an autoantigen common to all cells in the islet of Langerhans). Pancreatic islet-cell antibodies (ICA) are important markers for two subtypes of insulin-dependent diabetes mellitus and stain the entire islet in the standard immunofluorescence test. This could indicate either a mixture of antibodies each directed against one cell type, or a population of antibodies reacting with a single antigen common to the endocrine pancreas. In the present experiments such a common antigen was demonstrated visually by application of animal antisera raised to each of the 4 pancreatic hormones, together with ICA-positive sera in a four-layer double immunofluorescent technique employing green and red anti-Ig conjugates. Double exposure photographs demonstrated that the patients' sera reacted equally with the different endocrine cells. The ICA antigen did not cross-react with gastric glucagon- or somatostatin-cells. By contrast, human antibodies against glucagon-cells (GCA) or somatostatin-cells (SCA) reacted with discrete antigens specific to each cell type and in 50% of cases the antibodies also stained the respective endocrine cells in the gastrointestinal tract. These refined discriminatory properties of human autoantibodies may lead to a better understanding of the intracellular membrane systems in these important endocrine organs.


Polymeric IgA is complexed with secretory component (SC) on the surface of human intestinal epithelial cells. Viable suspensions of columnar cells were obtained from the surface and outer crypt epithelium of human colon mucosa by a combined treatment with citrate and EDTA solutions and mechanical disruption, but without the use of enzymes. A substantial fraction of the isolated cells contained free SC and secretory IgA in a cytoplasmic distribution that corresponded to previously reported immunohistochemical and immunoelectron-microscopical results obtained with tissue sections. On their surface the same cells were shown to bear SC complexed with J-chain-containing polymeric IgA, whereas only occasional traces of free SC were found. IgM was detected in the surface patches which contained the largest concentrations of SC and IgA. These findings demonstrate that in SC-producing epithelial cells SC molecules become exposed on the plasma membrane, thereby being able to bind specifically J-chain-containing IgA and IgM present in the tissue fluid. Such adsorptive complexing is probably a prerequisite for the selective pinocytotic transport of these two Ig classes through glandular epithelium in man.


HLA-D restriction of the macrophage-dependent response of immune human T lymphocytes to PPD in vitro: inhibition by anti-HLA-DR antisera. The response of T cells from sensitized individuals to low doses of PPD in vitro is macrophage-dependent. By testing different allogeneic combinations of macrophages and T lymphocytes, it was found that an optimal response required that antigen be presented by macrophages sharing at least one of the HLA-D determinants of the T cell donor. Antisera recognizing HLA-A, -B or -DR antigens were found to be able to inhibit this proliferative response. The anti-HLA-DR antisera were found to exert their inhibitory effect only when directed towards an antigen shared by the donors of the T lymphocytes and the macrophages. Anti-HLA-A and -B sera, however, had an inhibitory effect when reactive with the responding T lymphocytes, irrespective of their reactivity with the cooperating macrophages. It is concluded that an optimal secondary response of in-vivo-immunized T lymphocytes to PPD requires the combined recognition of the antigen and 'self' membrane structures encoded by the HLA-D locus.


Relationship of pregnancy-associated alpha2-glycoprotein (alpha2-PAG) to peripheral blood leucocytes. The high molecular weight plasma glycoprotein pregnancy-associated alpha2-glycoprotein (alpha2-PAG) can be demonstrated on the surface of blood leucocytes and is synthesized by oestrogen-stimulated cells in culture. By the use of an indirect immunofluorescence technique, pretreatment of leucocytes with anti-alpha2-PAG IgG revealed alpha2-PAG on C3 rosette-forming cells and monocytes but not on E rosettes. Lymphocytes treated with anti-alpha2-PAG showed markedly diminished ability to form Fc rosettes. A percentage ranging from 15% to 20% of leucocytes from normal adults of both sexes, pregnant and oestrogen-treated females were positive for alpha2-PAG but no obvious correlatin was observed between the incidence of alpha2-PAG bearing cells and plasma levels of the protein.


beta2-Microglobulin from normal and leukaemic guinea-pig lymphocytes. beta2-Microglobulin has been isolated in useful quantities from the urine of strain-2 guinea-pigs after either treatment with sodium chromate or induction of the L2C leukaemia. Antibodies raised against the beta2-microglobulin were used to set up a radioimmunoassay which measured its export into culture fluid by normal and leukaemic lymphocytes. Material containing beta2-microglobulin was also obtained by digestion of the lymphocytic surfaces with papain; fractionation demonstrated both free and combined forms, with no qualitative difference between those from normal and those from leukaemic cells.


Characterization of the DNA-synthesizing cells in rheumatoid synovial tissue. DNA-synthesizing cells from the rheumatoid arthritis synovial tissue of 7 patients and from 5 patients with traumatic and degenerative joint lesions were studied by incubating fresh synovial tissue samples with tritiated thymidine. Labelled cells were identified using autoradiography. The tissue sections were stained with methyl green pyronine. It was found that 0.66% (range 0.38-1.4) of the cells were labelled with 3H-thymidine whereas in control materials the percentage was 0.17 (range 0-0.38). Approximately half of the labelled subsynovial cells in rheumatoid patients (range 37-67%) were small lymphocytes, according to morphological criteria. About one-tenth of the labelled cells (range 0-17%) looked like medium-sized lymphocytes, while the rest had the characteristics of fibroblasts or were unidentifiable.


Serum beta-2-microglobulin in Sjögren's syndrome. The serum concentration of beta-2-microglobulin was determined with a radioimmunoassay in 52 patients with keratoconjunctivitis sicca, 29 of whom had Sjögren's syndrone. Eleven (38%) of the patients with Sjögren's syndrome had high serum values. These cases had a higher mean age and a higher frequency of the complete triad of Sjögren's and of antinuclear antibodies than had the lower value cases. The sicca components per se did not seem to influence the serum concentration of beta-2-microglobulin. Most of the few complications occurred in patients with high values.


[Therapeutic progress. Critical analysis of controled and non-controled clinical studies]. Methods used in the evaluation of therapeutic results in clinical oncology are criticized on the basis of recent examples of studies including the most-used antitumor agents. The need for random allocation of patients in comparative studies is underlined and the practical, statistical, and ethical limitations on randomization procedures are reviewed.


[Medical treatment of primary pulmonary neoplasms]. Primary cancer of the lung is the most frequent malignant tumor in Switzerland among males and its frequency is rapidly increasing among females. The rate of failure after curative treatment including surgery and/or radiotherapy is about 80%. A large proportion of lung tumors are already inoperable at the time of diagnosis, a fact which accounts for the importance of chemotherapy as a palliative treatment for lung cancer. Single drug chemotherapies are relatively ineffective, with an overall response rate of 20% and a response rate of up to 50% for small cell tumors. Combination chemotherapies attain a 50 to 90% response rate in small cell tumors while the rate of failure is 50% or more in other cell types. Published results of post-surgical adjuvant chemotherapy of lung cancer are equivocal, possibly due to unwanted differences in the selection of patients and in therapeutic schedule. It is still not demonstrated that adjuvant chemotherapy improves lung cancer treatment.


[The fiberoptic-endocopic intubation for the palliatuve treatment of malignant esophageal stenosis]. Fibreoptic-endoscopic dilatation and intubation is a relatively new and safe palliative treatment for patients with inoperable esophageal carcinoma. The procedure is described at length in three patients in whom it produced instant relief of dysphagia and rapid improvement of nutrition. The stay in hospital is reduced to a minimum. Possible complications are discussed.


Slow axonal transport of neurofilament proteins: impairment of beta,beta'-iminodipropionitrile administration. beta,beta'-Iminodipropionitrile (IDPN) administration prevented normal slow axonal transport of [35S]methionine- or [3H]leucine-labeled proteins in rat sciatic motor axons. Ultrastructural and electrophoretic studies showed that the neurofilament triplet proteins in particular were retained within the initial 5 millimeters of the axons, resulting in neurofilament-filled axonal swellings. Fast anterograde and retrograde axonal transport were not affected. The IDPN thus selectively impaired slow axonal transport. The neurofibrillary pathology in this model is the result of the defective slow transport of neurofilaments.


Palliation of inoperable head and heck cancer: combined intra-arterial infusion chemotherapy and irradiation. Palliation of unresectable head and neck cancer remains a difficult problem. Because of excellent results reported by others with infusion of vinblastine, methotrexate, and 5-fluorouracil into the external carotid artery followed by irradiation before curative surgery, we applied this technic to 22 patients with advanced head and neck cancer. Fifteen patients from this group who had chemotherapy infusion followed by radiation therapy are compared with 21 patients who received radiation therapy alone. Both groups were similar in distribution of primary site, histology, and TNM stage. Of 15 patients, 14 (93%) had partial or complete tumor regression after both arterial chemotherapy infusion and irradiation, while 14 of 17 patients (82%) receiving primary irradiation had partial or complete response. Drug toxicity and complications related to infusion occurred in all patients. Most patients in both groups had short survivals (mean of 14.1 months in infusion chemotherapy and radiation vs 9.1 months in primary irradiation). One patient remains alive in the infusion group and two in the control group; however, all have recurrent disease. Results indicate a slight increase in survival time with the addition of infusionchemotherapy to irradiation in palliative treatment of head and heck cancer.


Pharmacologic dilatation of the ductus arteriosus with prostaglandin E1 in infants with congenital heart disease. Prostaglandin E1 (PGE1) has been used for successful palliation in nine infants with congenital heart disease. Seven patients had pulmonary atresia with ductal-dependent pulmonary blood flow. In this group, systemic O2 saturation increased from a mean value of 45% to 79% after infusion of PGE1, and surgical palliation was successfully done with the infants in stable condition, without hypoxemia or acidemia. An additional patient with coarctation of the aorta had marked ductal dilatation after PGE1 infusion as indicated by umbilical artery pulse pressure. The coarctation was repaired, with the infant in stable condition. The final patient had neonatal tricuspid insufficiency with right to left atrial shunting. Systemic O2 saturation was improved after PGE1 infusion, though the ductus was closed. The improved oxygenation was believed to be due to a reduction in pulmonary vascular resistance by PGE1. Prostaglandin E1 provides a powerful new tool for palliation of critical congenital heart disease in infants whose ductal constriction can markedly influence their clinical status.


Pacreaticoduodenectomy.

Pacreaticoduodenectomy. Pancreaticoduodenectomy, the Whipple operation, is a reasonable operation for carcinoma if used in the absence of distant metastases or regional spread to vital structures. It can be performed with an acceptable in-hospital mortality. It is primarily a palliative surgical procedure. Occasionally, a patient will survive more than five years. At times, the operation is fully justified or cannot be avoided for nonmalignant conditions.


Fluids in the anterior part of the optic nerve in health and disease. New techniques have recently made it possible to study the flow of fluids (blood, axoplasm, and interstitial fluid) in the anterior part of the optic nerve. Blood flow has been reviewed previously; axoplasm and interstitial fluid are considered in this review. General concepts of axoplasmic transport (anterograde and retrograde) are outlined, and the role of axoplasmic transport in the pathogeneses of optic disc edema of various types, in glaucoma, and in ischemic and toxic optic neuropathies is discussed. The probable sources of interstitial fluid in the anterior part of the optic nerve are capillaries in the nerve itself, peripapillary choroid, vitreous, cerebrospinal fluid and possibly axoplasm in the local axons; the flow is defined by various barrier systems. The role of the interstitial fluid in the pathogeneses of optic edema (and associated phenomena) and in serous retinal detachment in the macular region associated with optic disc pit is discussed. Its involvement in the process of diffusion of retrobulbar medication into the optic nerve and vitreous is also considered.


Cheyletiellosis in long-haired cats.

Cheyletiellosis in long-haired cats. Among 41 catteries, the majority of which were investigated because of problems of chronic pruritus, 27 proved to be infected by Cheyletiella mites. The skin lesions consisted of small erythematous papules with crusts and some loose hairs. After removal of the loose hairs Cheyletiella mites could be collected with adhesive tape for microscopic examination. Human involvement (papular urticaria) was observed in 20% of the cases. Bathing with Lindane was an effective mode of treatment.


Inhibition of MLC responder and stimulator function with allo-antisera in rhesus monkeys. Ten antisera containing antibodies directed against specificities controlled by the Ia1 locus of rhesus monkeys were tested for their ability to inhibit the MLC reaction. In cultures with responding cells from the serum producer, all sera with anti-Ia1 activity depressed the stimulatory capacity of cells carrying the Ia1 antigen in question. In other responder/stimulator combinations, the stimulation-inhibition was Ia1-related for the majority of the antisera. These data provide further evidence for a possible identity (or close association on the cell membrane) between Ia1 and D locus determinants of rhesus monkeys. In addition, some sera showed an inhibitory effect also on responder cells (with cells from the serum producer as stimulators). There was no apparent relation of response inhibition to the Ia1 specificities detected by antisera.


Quantitation of HLA-D differences.

Quantitation of HLA-D differences. The predictability of MLC non-reactivity by HTC typing was tested in a single checkerboard experiment which involved 39 unrelated individuals belonging to 12 different groups of HLA-D identical phenotypes. The strength of one-way MLC reactions in all possible responder-stimulator combinations (39 X 39) was quantitated by the Linear Clustering Analysis Program. Individuals who, by HTC typing, were identical for two HLA-D antigens gave 51% negative, 36% intermediate and 13% strong positive MLC responses. Identity for only one HLA-D antigen resulted in 3% negative, 40% intermediate and 57% strong MLC reactions. When no HLA-D antigen was shared, 88% of the reactions were strongly positive. HLA-D antigens behaved as equipotent stimulators in MLC between half-identical pairs. The only exception consisted of the higher frequency of weak responses displayed by the Dw5 positive individuals against stimulators differing by LD107. The same pattern was observed when LD107 homozygous cells were used as stimulators, suggesting that determinants of this specificity might be partially included in Dw5.


Toxicity of the hexachlorocyclohexane in rats. Three groups, with 10 sixty-day-old male rats each, were given dietary levels of technical hexachlorocyclohexane (HCH) 0, 0.9 and 900 ppm for 90 days. Observations were made on blood glucose, live glycogen and glucose-6-phosphatase (G-6-Pase), organ weights, histology and histochemistry of different tissues. Significant findings included growth retardation at 900 ppm, increased relative liver weight at the same dietary level, reduction of blood glucose levels at 0.9 ppm while liver glycogen and G-6-Pase levels were not affected in any dosage. Histological and histochemical changes were seen only in liver and kidneys, including steatosis and gutular hyaline degeneration in the kidneys of animals receiving dietary levels of technical HCH 900 ppm.


Immune response-associated antigens on mouse leukemia cells. I. Detection of Ia antigens on GRSL cells. The expression of immune response-associated (Ia) antigens on the surface of mouse strain GR (H-2dx) ascites leukemia (GRSL) cell lines was studied by cytotoxic tests, immunofluorescence, and immunoprecipitation assays. Ia expression varied among the three GRSL cells lines (GRSL 2, GRSL 14, and GRSL 15) studied by cytotoxic assay. GRSL 14 cells showed the strongest expression of Ia antigens among these three cell lines. A time-course study of tumor growth in mice revealed that Ia antigens on the tumor cells demonstrated the strongest expression 10 days after injection of GRSL cells into GR mice, and that subsequently it decreased until the death of the animal. Cells treated with neuraminidase exhibited more readily detectable Ia antigens, expecially in the late stages of leukemia, which suggested that Ia antigens had been masked by sialic acid. Immunoprecipitation studies revealed that Ia molecules on the leukemia cell had the same molecular weight as those on the normal lymphocytes. Immunofluorescence studies disclosed that Ia antigens were distributed diffusely on the surface of the tumor cells.


Specificity of cellular migration into cardiac allografts in rats. The question has not been previously investigated as to whether host lymphocytes infiltrate vascularized organ allografts in indiscriminate fashion, or whether they are retained selectively because of specific antigenic recognition sites on their surfaces. By using a dual cardiac allograft model in LEW rats, we have examined this problem by two methods: (1) detection of preferentially accumulating cells selectively cytotoxic to allografts bearing specific transplantation antigens as compared with "third-party" allografts; and (2) examination of trafficking patterns of separate radiolabeled populations of sensitized cells adoptively transferred into double heart-grafted recipients. In the first series of experiments, using BN and BUF rats as donors, differences in specific cytotoxicity mounted by infiltrating lymphocytes harvested from the appropriate and inappropriate graft were moderately significant (P less than 0.05). Because the question of cross-reactivity betweeen BUF and BN antigen was raised, lymphocytes sensitized to BN and WF donors were differentially labeled in vitro with 3H- or 14C-thymidine. After mixture and adoptive transfer, the ratio of specific to third-party labels was measured in each graft. In this second series of experiments, significant (P less than 0.001) preferential accumulation of specifically sensitized cells were found in the appropriate vascularized organ allograft. These experiments confirm the results of other experimental models, and demonstrate that sensitized lymphocytes accumulate selectively in specific vascularized organ allografts.


Antigenic determinants of C3 and C4 complement components on washed erythrocytes from normal persons. Well-washed erythrocytes from normal persons were agglutinated by antisera to C3, C3d, and C4, and this agglutination was specifically inhibited by the corresponding C3 or C4 protein. C3 and C4 antigenic determinants were present on the red blood cells of freshly shed blood promptly anticoagulated with EDTA, heparin, ACD, or CPD, and no significant changes in degree of agglutination were observed on storage of EDTA or CPD blood for two weeks at 4 C. Marked differences in degree of agglutination by anti-C3, anti-C3d, and anti-C4 were observed when erythrocytes of 16 normal persons were assayed, and significant correlations were obtained when the quantitative results with any two antisera were compared. Anti-C3c did not agglutinate erythrocytes from normal persons, suggesting that the C3 antigens detected on normal cells are carried by the C3d fragment. To avoid significant agglutination of the erythrocytes from some normal persons, very dilute preparations of anti-C3, -C3d, and -C4 had to be used for instrumented diagnostic direct antiglobulin tests. Stronger reagents could be used for indirect antiglobulin tests when the result of a suitable control could be subtracted.


[Significance of the embolization of the arteria renalis for the treatment of kidney tumours (author's transl)]. In 24 patients with malignant kidney tumours percutaneous embolizations of the arteria renalis were performed in about 1 year. The material for embolization was gelatine-sponge-particles. The embolization was done pre-operatively, usually in connection with the arteriographic examination of kidney tumours (hypernephroid carcinoma). In 2 patients without operation it was done as a palliative measure. Our favourable results to improve the operability of tumours agree with reports in the literature. According to our opinion the pre-operative embolization of the arteria renalis with kidney tumours offers the possibility of a blood-sparing operation and a reduction of tumour-cell outwashings.


Post-prostatectomy incontinence.

Post-prostatectomy incontinence. Urinary continence is maintained by the smooth-muscled system of the "internal sphincter". The striated external sphincter is not primarily responsible for continence. One of the chief functions of the external sphincter is the initiation of voluntary micturition. Its other functions are: random interruption of the urinary stream, reflex control during an increase in intra-abdominal pressure (such as coughing, sneezing, larghing, lifting) complete emp;ying of the urethra after micturition and stabilization of the posterior urethra in the urogenital diaphragm. After prostatectomy an intact external sphincter is important in order to support the smooth-muscled system which continues to be primarily responsible for continence to function as efficiently as possible. In approximately 90% of all postprostatectomy incontinences the external sphincter is intact and this cames a good prognosis following our correcture surgery without the need for prostheses. Only in rare post-prostatectomy incontinence cases (aprox. 10%) is the external sphincter also injured. Incontinence surgery according to our method has not been satisfactory in these cases.


Steroid receptors in human prostatic cancer a preliminary evaluation. The determination of steriod-receptors in human prostatic tissue from 68 patients with benign prostatic hypertrophy (BPH) and 36 patients with prostatic cancer by the method of cold agargel-electrophoresis is described. The results are discussed in the light of several problems inherent to this assay. There are certain indications that there is a correlation between steroid-receptor values and response to endocrine therapy.


[Use of heterologous antistaphylococcal gamma-globulin in treating suppurative mastitis]. The effectiveness of heterologic antistaphylococcal gammaglobulin was studied in the clinic in 67 cases of acute lactogenous mastitis. The activity of the preparation was 200 A. E/ml. The Bezredko method of injection was used--l ml once a day during 5 days. The treatment resulted in the decrease of intoxication, purification of the surgical wound, normalization on non-specific protection factors, rise of antistaphylococcal antitoxin titers and decrease of autosensitization phenomena.


Site of initiation of the plasma cell reaction in the rabbit lymph node. Ultrastructural evidence for two distinct antibody forming cell precursors. Two times sublethal total body-X-irradiation with weekly local thymus irradiation established a T-cell deprived experimental model in rabbits. Humoral immunity reactions in draining lymph nodes have been analyzed histologically and at the submicroscopical level after challenge with Salmonella Java vaccine, horse spleen ferritin, horse-gamma-globulin, a chemical sensitizer oxazolone (2 phenyl-4-ethoxymethylene-5-oxazolone) and after skin allografting respectively. The time sequence studies in these animals with an 'isolated B-cell system' are compared with similar experiments in normal non-irradiated rabbits. The site of initiation of the thymus-independent and thymus-dependent plasma cell response is established in the lymph node. The (ultra)structural features of the antibody forming (-B-)cell precursors, the marginal zone cells, are described and discussed. The differentiating off-spring of two (sub)microscopically recognizable plasma cell lines is presented.


Histophysiology of cellular immunity reactions in B-cell deprived rabbits. An X-irradiation model for delineation of an 'isolated T-cell system'. Three times sublethal total body X-irradiation with thymus shielding--at 2 weeks' intervals--delineated a temporarily B-cell deprived animal model, only reconstituted with recently thymus-derived cells. The thymusdependent areas of peripheral lymphoid tissue-repleted with T-cells--are described. The cellular immune capacity of these animals with an "isolated T-cell system" was analyzed by means of skin allografting. Histological and autoradiographic studies were performed in draining lymph nodes after a variety of antigenic stimuli: skin allografts, S. java vaccin, horse-gamma-globulin, horse spleen ferritin and a contact sensitizer (Oxazolone).


[Effect of streptovaricin on the multiplication of L line cells]. An inhibitor of the reverse trascriptase-streptovaricin in a dose of 4 mkg/ml would induce an increase of the DNA amount in L cell nuclei, while its dosage of 8 mkg/ml decrease the amount of DNA, resulting in the differentiation of some population cells. Streptovaricin inhibited the L cell multiplication, rendering no significant effect on that of normal fibroblasts of C3H mice culture.


[Sideeffects of colloids (author's transl)]. A prospective controlled trial during 1975 and 1976 has revealed that none of the colloids in clinical use (plasma protein solution, gelatine, hydroxyethylstarch and dextran) is free from the risk of anaphylactoid reactions. Even though the incidence of anaphylactoid reactions is low (0.03%), lethal outcome might be encountered. Between the colloids differences exist as far as manifestation (skin, circulatory and respiratory system) and degree of severity (I--IV) of anaphylactoid reactions are concerned. Since the underlying pathomechanisms have not been elucidated yet, true prophylactic measures are unknown. Therefore, it is mandatory to control the patient very carefully at the beginning of infusion; early symptoms of anaphylactoid reactions should trigger immediate therapeutic measures. Recent findings showed that the anaphylactoid reactions to dextran might be elicited by immune complexes. A new model was developed to investigate the chances of specific prophylactic procedures.


[Cryosurgical treatment of rectal carcinoma (author's transl)]. After comprehensive experimental especially morphological studies in animals, we started cryo-therapy of rectal carcinoma in 1972. We now present the first critical 5-years review concerning indication, clinical results and cryo-immunological features. In strongly indicated cases local tumour destruction by extremely low temperatures is superior to other palliative methods. Of 67 patients with rectal carcinoma treated with cryosurgery, 37 survived, 12 more than 36 months and 16 more than 24 months. Though there are only few hints indicating an increased immunological response following cryo-surgery, our investigations suggest a general influence on host's immunity by cryo-therapy.


[Therapy and therapeutic results in malignant ovarian tumors (exerience report 1945--1976)]. The study is the result of the medical histories from the Womens Hospital Cottbus from 1945 to 1976 with 387 malignoms of the ovary. The patients material is classified according therapeutic groups. The 5-year survival rates of 345 patients from 1945 to 1971 are 25,9%. The therapy of the ovarian malignoma consists of a combination therapy comprising, according to the stage, operation, radiation therapy and, since 1959 application of cytostatica.


[Demonstration of the neurosecretory hypothalamo-rhombencephalic junction in rats by the retrograde axonal transport of horseradish peroxidase]. The retrograde transport of horseradish peroxidase (HRP) was used to demonstrate the neurosecretory hypothalamo-hindbrain connection of the rat. Following HRP injections into the region of the dorsal columns nuclei labeled cells were observed in the caudal part of the paraventricular nucleus and in the lateral hypothalmic area. Hypothalamo-hindbrain projections are predominantly uncrossed.


Anti-thyroxine and anti-triiodothyronine antibodies in three cases of Hashimotos thyroiditis. Antibodies against thyroxine (T4) and/or triiodothyronine (T3) were detected in 3 patients with Hashimoto's thyroiditis. One of the patients had both anti-T4 and anti-T3 antibodies and the other 2 patients had only anti-T3 antibody. Serum T4 or T3 antibodies and the other 2 patients had only anti-T3 antibody. Serum T4 or T3 values measured by the single antibody radioimmunoassay (RIA), were low or nil in these patients. One patient was mildly hypothyroid. The other 2 patients were clinically euthyroid, but they were considered latent hypothyroid because of a slight elevation in serum TSH. On extraction of the sera with ethanol, high or normal values of T3 were obtained in all cases. Recovery of T4 or T3 added to the patients' sera determined by RIA was significantly low. The binding of [125I]T4 or [125I]T3 to the patients' sera was demonstrated by the polyethylene glycol method and by using RIA kits without adding the antibody provided. The binding activity was localized in the IgG fraction by column chromatography and by immunoprecipitation. T4- or T3-binding protein in two sera migrated in the gammaglobulin region on paper electrophoresis and was found in 7S fraction on Sephadex G-200 chromatography. In one serum containing both anti-T4 and anti-T3 antibodies, the association constants (Ka) for binding of T4 and T3 were 3.8 x 10(8) l/mol and 1.7 x 10(8) l/mol, respectively. The binding capacities in the serum were 8.2 microgram of T4 and 1.9 microgram of T3 per 100 ml of serum. For two sera containing anti-T3 antibody, Ka were 5.5 x 10(8) l/mol and 7.4 x 10(10) l/mol, and the binding capacities were 0.6 microgram/100 ml serum and 0.7 microgram/100 ml serum respectively. The clinical significance of these antibodies is discussed.


[Should we still operate small cell carcinoma of the lung? (author's transl)]. Two hundred and nineteen cases of small cell carcinoma of the lung are reviewed. The 5-year survival rate is less than 5%. Four patients survived more than 5 years, among 9 tumors resected with curative intention. Palliative resections do not enhance the survival rate. Combined radiotherapy and polychimiotherapy have a high response rate and tend to extend the median survival interval. Thus, small cell carcinoma require an accurate pathological diagnosis and extensive staging. Only small, localized peripherical tumors (T1N0M0, T2N0M0) should be resected.


[Surgical treatment of rectal cancer (author's transl)]. The authors report there surgical experience with rectal cancer. From 1963 to 1974, 346 patients were hospitalized, of which 359 were operated, which constitute a operatory rate of 98%. A exeresis was performed in 85% of the cases. Briefly, the authors use two types of operation : an anterior resection and an abdominoperineal amputation of the rectum with two synchronized teams--the operation of Lloyd-Davies--which constitutes an obvious progress compared to the operation of Miles. The overall postoperatory mortality remained high : 8.8% which represents 10.1% for the operation of Lloyd-Davies, and 6.7% for the anterior resection. Two hundred and twenty-four patients have been operated with a follow-up of at least 5 years; 4 [1.6%] were not reseen and are considered deceased. The overall survival at 5 years was 36.4%. The survival rate at 5 years, not corrected, of operations including an exeresis was 43.1% which represents 37.2% for the operation of Lloyd-Davies and 51.2% for the anterior resection. This survival rate includes all patients operated and not only those who survived the operation.


Alteration of developing and adult rat muscle membranes by zuclomiphene and other hypocholesterolemic agents. The present study presents evidence for a third hypocholesterolemic drug, zuclomiphene, being able to induce an experimental myotonic condition. Other drugs used singly or in combination were AY-9944, Triparanol and 20, 25-diazacholesterol. It has also been demonstrated for the first time that experimental myotonia can be induced in developing rats as well as adults. Developing rats received the initial intraperitoneal injections of drug at 5 days of age and were examined at 50 days of age. Adult rats were treated for 5 weeks. Two injections were given per week. Positive electromyography findings were observed in the developing and adult animals receiving 20, 25-diazacholesterol and zuclomiphene. The electromyography data of the other regimens of treatment were equivocal with regard to myotonia. Histological, histochemical, and electron microscopic examination of the muscle demonstrated no important changes. estimation of sterol composition showed that desmosterol was a major sterol in muscle after 20, 25-diazacholesterol or zuclomiphene treatment, thus furthering the concept that it is desmosterol in the muscle membrane, and not the drug, that is responsible for the myotonic condition.


The effect of supervised tooth cleansing every second week on dental caries in Danish school children. The purpose of the present study was to determine the effect of a program of regular plaque control carried out by a group of school children, supervised and assisted by dental personnel. Approximately 200 children 5--13 years of age were randomly assigned to two groups. Children in the experimental group performed supervised toothbrushing every second week during the school year, using a disclosing solution. Following this, a disclosing solution was reapplied and the remaining plaque removed by dental personnel. Both groups participated in fortnightly fluoride rinses, regular toothbrushing instruction and various educational activities. Mean dental caries increment at the precavitation level during the 2-year experimental period was 19 per cent lower in the experimental group than in the control group. At the cavitation level the difference was 17 per cent. None of these differences were statistically significant. The conclusion of the present study was that only limited effect of regular removal of dental plaque as performed by school children could be demonstrated.


[Bacteremia and tonsillectomy].

[Bacteremia and tonsillectomy]. A comparative study on the course of bacteremia and the postoperative behavior in 132 patients requiring tonsillectomy and adenoidectomy has been conducted. A control group including 33 patients was compared to three groups of an even number of cases treated with either doxycycline or amoxycyllin, or receiving gamma globulin immunotheraphy. Choice was guided by (1) the occurrence of bacteremia during surgery and the search for the various microbial strains involved, and (2) the confirmation of the advantages of the drug used within the first week of treatment.


The anal transitional zone. A method for macroscopic demonstration. The anal canal extends from the upper to the lower border of the internal sphincter. The canal can histologically be divided into three zones according to the epithelial lining, being of colo-rectal type in the upper part and squamous in the lower part, while the middle part, where the epithelium varies, is called the anal transitional zone (ATZ). This zone can be demonstrated macroscopically using whole mount staining with Alcian dyes, which reveal it as light green or blue, contrasting to the dark stained rectal type mucosa above and the unstained squamous epithelium below. Comparison with histological section shows that this zone corresponds with reasonable accuracy to the anal transitional zone.


Crossed immunoelectrophoretic analysis of Neisseria meningitidis antigens and of corresponding antibodies in patients with meningococcal disease. Sixty-three different antigens of Neisseria meningitidis groups A, B and C were demonstrated by means of crossed immunoelectrophoresis against rabbit antiserum. The group-specific polysaccharides A and C were identified in the immunoprecipitate pattern. The majority of the remaining antigens were common to all three groups of meningococci. A clearcut rise in antibodies was found in all of 27 patients with meningococcal meningitis or septicaemia. These antibodies were directed against both group-specific antigens and common antigens. No such rise was seen among the 22 patients with purulent meningitis of non-meningococcal etiology. Altogether 15 precipitins were detected in the patients with meningococcal disease. Nine of these antibodies could be identified by comparison with the rabbit antiserum. The antibody rise was semiquantified by means of a scoring system. The rise in the precipitin score of antibodies against common antigens in patients infected with group B meningococci was significantly higher than in patients infected with group A meningococci.


Fluorescent staining of hair cells with ethidium bromide. The present study evaluated ethidium bromide, a nucleic acid-specific fluorescing stain for cochlear applications. Tissue exposed to acoustic stimulation did not exhibit the loss of fluorescence in hair cells described in studies on other fluorescing stains. The ethidium bromide fluorescence technique was, however, found to be useful in detecting subtle damage in cell nuclei even before gross structural alterations in cochlear cytoarchitecture appeared. The implications of the use to ethidium bromide staining for histologists are discussed.


Competence-related increased enzyme release from Streptococcus sanguis (Wicky) cells. The ablity of competent and noncompetent Streptococcus sanguis (strain Wicky) cells to release enzymes to the environment was studied. Both competent and noncompetent cells leaked the enzymes tested (aldolase, phosphatase and deoxyribonuclease), but the activities liberated from the competent cells were always roughly 2-fold higher than those released from noncompetent cells. This increased enzyme leakage from competent cells occured in all kinds of media and procedures employed. The leakage of enzymes followed a time-dependent kinetics (different for aldolase and phosphatase), was temperature sensitive and had a pH optimum. The increased enzyme release was most likely not due to cell disruption, but seemed to be rather a consequence of alteration in cell barrier permeability. These results strongly support the "unmasking" model proposed for explanation of competence development in bacteria.


Respiratory mutation and galactose metabolism in yeast Saccharomyces cerevisiae. Restriction in growth on galactose as unique source of energy due to respiratory deficiency resulting from mutation in a gene gal probably different from gal 3 is described.


Genetic properties of the Salmonella enteritidis R404 plasmid aggregate. II. Separation of plasmids by transformation. Transformational separation of plasmids from R404 plasmid aggregate found in Salmonella enteritidis strain was performed. Three classes of transformants differing in their resistance patterns were isolated. Genetic properties of the transformants suggest that their resistance is determined by single plasmids. Plasmid pCK3 (Tra-ApCbCrSuSm) and pCK4 (Tra-ApCbCrCm) are nonconjugative while plasmid pCG1 (TraApCbCrSuSmTcKmNm) is conjugative. Separation of all plasmids of R404 plasmid aggregate allowed to determine their genetic properties and the manner of conjugational transfer of R404 plasmid aggregate R-determinants.


Polypeptide antibiotic 26a from Bacillus subtilis. I. Taxonomy and fermentative production. In surface cultures on NK/2-Sym's medium, the isolate No. 26a of Bacillus subtilis from the intestinal tract of Galleria mellonella larvae produced three antibacterial substances which were separated by gel filtration on Sephadex G-25 column. The major bioactive compound named 26a had a close resemblance to bacitracin family of polypeptide antibiotics. Two minor active compounds, i.e. a bacteriolytic enzyme with endo-beta-N-acetylmuramidglycanohydrolase (EC. 3. 2. 1. 17) activity and other unidentified factor were usually synthetized in trace amounts. Maximum yield of 26a generally occurred after 120 hour incubation, when the producer reached the stationary growth phase and general sporulation of the bacterial cultures was found. The basal medium of NK/2-Sym supplemented by addition of manganese ions (10(-4) M), d-glucose (1%) and inorganic nitrogen beneficially resulted in antibiotic potency of the fermentation broth. The antibiotics produced by other isolates (Nos 5AK, 15 and 92) have been also analyzed and from their properties they can be tentatively classified as members of bacitracin group polypeptides. A possible role of the antibiotics produced by intestinal Bacillus spp in the formation process of typical gut microflora of G. mellonella is discussed.


Polypeptide antibiotic 26a from Bacillus subtilis. II. Isolation and purification procedures. Both the analytical and preparative methods by which the preparations of 26a bydrochloride salt with a high antibacterial activity and 20--30% recovery have been obtained from the fermentation fluids of Bacillus subtilis are presented. On an industrial scale the antibiotic can be yielded by absorption of bioactivity on Amberlite CG-50I column and precipitation with picric acid of crude substance from active elutes as adduct which was divided on equilibrated CM--cellulose and finally purified by gel filtration on Sephadex G-25 column. The purified preparation gave a single band by SDS-polyacrylamide gel electrophoresis and one ninhydrin-positive spot by thin-layer chromatography on silica gel G plates corresponding to single zones of bioactivity on bioautograms, and moved as a single peak of almost constant antibacterial activity on Sephadex G-75, G-100 and G-200 columns. The potency of the purest preparations, lot Sephadex G-25, was 6,500--7,000 arbitrary units/mg, and were characterized as follows: purification factor, 57; purity of 98--100% by densitometer scans of SDS-polyacrylamide gels; MIC for Sarcina lutea by twofold agar dilution assay, 0.306 microgram/ml.


Effect of various nitrogen salts in beet pulp medium on polygalacturonase activity of Penicillium sp. 7/4B/EI 1 mutant. The highest PG activity was obtained in beet pulp with (NH4)2HPO4 in amount equivalent to 0.14--0.28% N after 7 days of growth; At optimal concentration, (NH4)2HPO4 did not influence the biomass production, but increased the pH of the culture media to above 6.0. The PG was an extracellular enzyme, acting mainly on highly esterified pectin. The attack was of a random manner, characteristic for the endo-enzymes. The enzyme was active at temperature 20 degrees C--40 degrees C and pH 5.0--6.0.


Activity and distribution of bacteriolytic N-acetyl-muramidase during growth of Acanthamoeba castellanii in axenic culture. Bacteriolytic endo N-acetylmuramidase of Acanthamoeba castellanii has been studied. In amoeba cells the enzyme, like exo N-acetylglucosaminidase and acid phosphatase, is attached to the lysosomes, as it is sedimentable when homogenates are prepared in medium containing sucrose. The sedimentability could be abolished by treatment with Triton X-100, thermal disintegration or by osmotic shock. The sedimentability and acid pH optima of the enzyme are highly characteristic of lysosomes. However, in young cultures over 50 per cent of enzyme activity was secreted by amoeba cells to the environment. The enzyme activity changed with the phase of growth cycle. The activity of enzyme expressed as units per mg of amoeba protein or per constant number of cells has been found to increase over 10 fold on aging of amoeba cultures. The increase in enzyme activity was stopped by actidione. The possible mechanisms of the regulation of the activity of lysosomal enzyme synthesis by amoebae are discussed.


Fluorescent pigments in the newly isolated methylotrophs: Pseudomonas J16 and Methylomonas Pl1. The pigments showing fluorescence maxima at 390, 366, 450-460 and 520 nm at excitation wavelength 254, 366 and 450 nm respectively, were detected in the cells and culture media of the obligate methylotroph Methylomonas Pl1 and facultative methylotroph Pseudomonas J26. The maximum at 520 nm is associated with the occurrence of a flavin pigment enabling growth of Lactobacillus casei E ATCC-7469 on the vitamin B2 deficient medium. The remaining fluorescence maxima are related to the prosthetic group of methanol dehydrogenase.


Studies on the morphology of colonies of bacilli of BCG-Poland substrain. I. The influence of iron on the type of BCG-Poland colonies. The influence of iron concentration in Sauton's medium solidified with agar on the type of colonies of BCG-Poland substrains, BCG-Rio de Janeiro, BCG-France, BCG-Denmark and BCG-Japan substrains has been examined. Of all the studied BCG substrains only the BCG-Poland substrain formed rough (R) and smooth (S) colonies. In the investigated substrains rough colonies became smaller with the decrease of iron concentration but they retained their characteristic surface roughness. The smooth colonies which in the same conditions appeared only in BCG-Poland substrain did not display such dependency on iron concentration. When the incubation period was prolonged secondary rough colonies appeared among the smooth ones, regardless of the iron concentration in the medium.


Studies on the morphology of colonies of bacilli of BCG-Poland substrain. II. Dissociation of BCG-Poland substrain on Löwenstein-Jensen egg medium. The dissociation of colonies of the substrain BCG-Poland on Löwenstein-Jensen medium has been studied. It had been stated previously (Lipińska and Rzucidło, 1974) that BCG-Poland substrain undergoes a process of dissociation which manifests itself in the appearance of smooth colonies alongside typical rough colonies. Attempts have been made to obtain pure culture of both colony types. Pure cultures composed of smooth or rough colonies respectively were obtained. The morphology and diameter of the smooth colonies depended on the size of the seed inoculum spread on the medium.


Extracellular release of organic products and growth of bacteria in Anabaena cylindrica (blue-green alga) culture. The studies were made with stationary cultures of Anabaena cylindrica (blue-green alga). The bacterial microflora accompanying blue-green algae is subject to succession and elimination in the course of growth. The bacteria are able to utilize organic products released by the blue-green algae. The products released by A. cylindrica to the environment are peptide-like compounds.


Antigenic glycopolypeptides HA1 and HA2 of influenza virus haemagglutinin. II. Reactivity with rabbit sera against intact virus and purified undissociated haemagglutinin. Rabbit sera produced against either intact virus or purified undissociated haemagglutinin were examined for reactivity with highly purified haemagglutinin glycopolypeptides. Sensitive radioimmunoassay for 125I-labelled glycopolypeptides revealed antibody reactive with either glycopolypeptide HA1, or glycopolypeptide HA2. Antibodies against the carbohydrate moiety were responsible only for a part of the binding activity. Under the conditions employed, the binding activity for glycopolypeptide HA2 was much stronger than for glycopolypeptide HA1. Competition assays suggested that immune reactivities were due to distinct antibody populations (i.e. with a specifity for glycopolypeptide HA1 and glycopolypeptide HA2, respectively). The immune reactivity to both haemagglutinin constituents, glycopolypeptides HA1 and HA2, was also shown by gel double diffusion. The precipitin line(s) corresponding to glycopolypeptide HA1 was (were) usually more distinct than precipitin line(s) corresponding to glycopolypeptide HA2. The glycopolypeptides HA1 and HA2 showed the reaction of nonidentity in immunodiffusion analysis.


Demonstration of neurosecretory substance in previously scanned specimens: adaptation of the Gomori aldehyde-fuchsin method for correlative SEM/TEM/LM histochemistry. The Gomori aldehyde-fuchsin (AF) method for selective staining of neurosecretory substance (NSS) has been adapted to tissue previously prepared for both scanning and transmission electron microscopy (SEM/TEM). The procedure results in precise correlation of light microscopic (LM) histochemistry with SEM/TEM of the same tissue.


Indirect methods of assessing thyroid function. Protein-bound iodine and thyroxine by column chromatography, a 1976 CAP survey. An assessment of the infrequently performed protein-bound iodine determinations (PBI) and thyroxine (T4) determinations by column chromatography is presented after analysis of data contributed by participants in the 1976 College of American Pathologists Chemistry Survey Programs. The two technics yield comparable mean concentrations, but there is considerable interlaboratory variance within method groups, especially among laboratories performing column chromatographic T4 iodine assays.


Comparison of the effects of sleep, exercise and autonomic drugs on ventricular extrasystoles, using ambulatory monitoring of electrocardiogram and electroencephalogram. Ambulatory monitoring of the electrocardiogram (ECG) and the electroencephalogram (EEG) in 12 untreated patients with frequent ventricular extrasystoles showed a significant decrease in both ventricular extrasystoles and heart rate during sleep. The decrease in ventricular extrasystoles correlated more closely with the change in heart rate than with the level of arousal. During wakefulness, similar changes in ventricular extrasystoles and heart rate could be produced by the intravenous administration of propranolol and, to a lesser extent, by phenylephrine. Exercise produced an initial increase in ventricular extrasystoles, with suppression at higher levels in most patients. Thus, the frequency of ventricular extrasystoles is usually reduced at both extremes of heart rate, and the changes that occur during sleep can be explained by autonomic mediation, with the sympathetic limb of the autonomic nervous system having a greater effect than the vagus.


Whipple's disease of the lung.

Whipple's disease of the lung. Described here is a unique case of Whipple's disease in a 54 year old man with chronic severe cough and gastrointestinal symptoms in whom the initial diagnosis of Whipple's disease was made by lung biopsy. This is, to our knowledge, the first reported case in which the bacilliform structures of Whipple's disease have been demonstrated in tissues from other than the gastrointestinal tract of lymph nodes. Subsequently, a peroral biopsy of the small intestine was performed and revealed identical and pathognomonic features of Whipple's disease. The pulmonary roentgenologic findings are described and the histologic differential diagnosis of histiocytic infiltrates in the lung, which may be histologically similar to Whipple's disease, are briefly reviewed.


Automated treatment for flight phobia: a 3 1/2 year follow-up. The authors contacted 43 patients who had been given audiovisual treatment for flight phobia 3 1/2--5 1/2 years previously. Of the 26 subjects who had flown successfully by the end of treatment, 23 had maintained their ability to fly at follow-up. Eighteen said their attitude toward flying was more positive since treatment, and 21 rated their comfort level while flying as "much better" or "better"; however, only 3 said they were "cured." Eleven patients said the treatment had helped to alleviate other fears or anxieties.


Treatment of liver cancer with regional intraarterial 5-FU infusion. The results of a retrospective three year study of forty-six patients with cancer of the liver treated with regional intraarterial infusion of 5-FU are reported. No primary mortality was noted. Oblective overall remission rate was 43 per cent. Overall median survival from onset of treatment was six months. The one year survival rate  was 33 per cent and the two year survival rate 11 per cent. Patients with an objective response had a significantly prolonged survival as compared with nonresponders, especially in the colorectal group: sixteen months versus four months. Survival was not related to tumor size and involvement of the liver. During treatment 42 per cent of the patients developed extrahepatic metastases. Quality of life was improved in 63 per cent of the patients. The results indicate that infusion therapy induces reasonable response and palliation but is inadequate for the control of extrahepatic tumor growth.


Histopathologic findings after cis-platinum bleomycin therapy in advanced previously untreated head and neck carcinoma. Eleven patients with unresectable or marginally resectable (stage III and IV) cancer of the head and neck were treated according to protocol with preoperative chemotherapy, surgical resection, and postoperative radiotherapy. Chemotherapy consisted of a combination of cis-diamminedichloroplatinum (II) (cis-DDP), 120 mg/M2, and bleomycin, 15 mg/M2, given sequentially during a three week treatment period. Seven patients initially had unresectable lesions which became amenable to surgical resection after chemotherapy. All eleven patients had approximately a 25 to 100 per cent reduction in tumor size. Histopathologic examination after chemotherapy showed a marked tendency towards cellular differentiation and keratin formation. Tumor necrosis was conspicuous by its absence. These histologic changes appear to be different from those seen after the use of other chemotherapeutic agents and radiotherapy. The histopathologic results closely resemble those found after the administration of bleomycin alone, although considerably accentuated.


Standardization of allergen extracts with appropriate methods. The combined use of skin prick testing and radio-allergosorbent tests. The paper presents recommendations for standardization of allergen extract by the combined use of skin prick tests and radioallergosorbent tests. These tests provide appropriate means for quantitation of the total allergenic activity of an extract. Advantages and limitations are discussed with reference to the literature.


Cerebellar afferents from the paramedian reticular nucleus studied with retrograde transport of horseradish peroxidase. Details in the cerebellar projections from the paramedian reticular nucleus (PRN) were studied in cats and monkeys by means of retrograde axonal transport of horseradish peroxidase (HRP). In the cat the majority of the fibres projects to the anterior lobe and to the vermis of the posterior lobe (with the exception of lobules VIIB and VIIIA). A less conspicuous projection was found to the lobulus simplex, the crura and the flocculus. The cerebellar nuclei, the paramedian lobule and the paraflocculus appear to be weakly connected with the PRN. A similar distribution of the cerebellar afferent fibres was found in the monkey material. The three subgroups of the PRN in the cat are not equal in their projection. The dorsal group appears to be connected with the greater part of the cerebellar cortex and with all nuclei. The ventral group lacks a connection with lobulus IX, the flocculus and the paraflocculus, and the accessory group appears to have its strongest connection with lobulus I (lingula), the flocculus and the vermal lobules VII-X. The findings are discussed in relation to other studies on the efferent and afferent connections of the nucleus.


The effect of cromolyn sodium on hypoxia-induced histamine release. In 16 guinea pigs the pulmonary circulation was isolated from the pulmonary systemic circulation and perfused with Tris buffer or with Tris buffer containing cromolyn sodium. The lungs were first ventilated with 100% O2 and then 100% N2 to induce alveolar hypoxia. The effluent was collected from the aorta and assayed for histamine by the fluorometric method. In all seven animals perfused with Tris alone (no cromolyn) a marked elevation of the effluent histamine was demonstrated. In the group perfused with buffer containing cromolyn there was a substantial diminution in the response to hypoxia. Therefore, cromolyn sodium partially blocked hypoxia-mediated histamine release.


Immediate (IgE-mediated) skin testing in the diagnosis of allergic disease. Immediate (IgE-mediated) skin tests are widely used in the diagnosis of allergic diseases. Skin tests correlate well with more specialized studies (RAST, histamine release and provocation tests) in the diagnosis of allergic disease. Lack of standardization and quantitation of biologic potency of allergens make critical comparison of skin test results impossible. A survey of practicing allergists yielded widely divergent opinions concerning the effect of anti-allergic drugs on skin tests. The results of published studies indicate that only antihistamines cause significant depression of skin reactivity. Therefore, therapy for asthma may be continued while diagnostic skin testing is in progress, avoiding the possible morbidity associated with discontinuing pharmacologic therapy.


[Allergy to suxamethonium. Case report]. The authors describe a clinical case of an allergy to suxamethonium (succinylcholine) chloride which prompted--a posteriori--an allergological work-up. This, in turn, demonstrated all the factors favoring histamine-release: atopic predisposition, tendency of nonspecific histamine-release, and real allergy to the muscle relaxant. This study has enabled the induction of anaesthesia without any problems, by avoiding the allergens through preventive therapy.


[The humoral immune response in recent pulmonary tuberculosis (author's transl)]. The average serum concentration of immunoglobulins, alpha-1-antitrypsin, haptoglobin and alpha-2-macroglobulin, calculated in 45 adults with pulmonary tuberculosis increased in a variable way for each of the six parameters studied. Tuberculosis does not induce new correlations between the parameters but modifies the intensity of existing links.


Therapeutic efficacy of inosiplex (Isoprinosine) in rhinovirus infection. Inosiplex (Isoprinosine), the paracetamidobenzoic acid salt of inosine dimethylaminoisopropanol, has shown antiviral activity in cell culture and in animals. Controlled challenge studies using the drug in a prophylactic fashion, however, have been disappointing. In vitro studies, as well as uncontrolled clinical trials, have suggested that the drug might be more effective when used therapeutically. We therefore undertook to test inosiplex in a controlled, double-blind, therapeutic study of volunteers challenged with rhinovirus. Thirty-nine volunteers were randomly divided into groups receiving either inosiplex or placebo tablets. Drug or placebo was started either at the time of, or 48 hours after challenge with rhinovirus Type 21. Illness was assessed in terms of the classical common cold symptoms, and infection was also determined by viral isolation from daily nasal wash specimens and by serum antibody rises. Five of 19 volunteers in the inosiplex group became ill, whereas 14 of 20 in the placebo group were sick (p less than 0.01). There was no difference between the control and inosiplex groups in the number of volunteers from whom rhinovirus was isolated. There was, however, a reduction in the duration of virus shedding in the inosiplex group. Seroconversion was also slightly less common in the inosiplex group. Immunologic studies suggest that inosiplex stimulates the lymphocyte mitogenic response. The results suggest that inosiplex exerts significant therapeutic benefits in rhinovirus infection.


Base specificity in the inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases by antitumor drugs. Adriamycin, daunomycin, acridylmethanesulfonanilide, and alkoxybenzophenanthridine alkaloids (coralyne acetosulfate, fagaronine chloride, and nitidine chloride) inhibit template-directed nucleic acid polymerizing enzyme activities like reverse transcriptase, DNA polymerase, and RNA polymerase. Enzyme reactions with poly(dA-dT), poly(rA)-oligo(dT) and poly(dA)-oligo(dT) are more strongly inhibited by the drugs than those with poly(dC)-poly(dG) and poly(rC)-oligo(dG). These results suggest that the antitumor drugs inhibit nucleic acid polymerases by a specific interaction with A:T base pairs of the templates.


Inactivation and inhibition of Rous sarcoma virus by copper-binding ligands: thiosemicarbazones, 8-hydroxyquinolines, and isonicotinic acid hydrazide. We have shown that three types of copper-binding ligands, thiosemicarbazones, 8-hydroxyquinolines, and isonicotinic acid hydrazide and their copper complexes, inactivate the transforming ability of RSV and inhibit its RNA-dependent DNA polymerases. Three other compounds, 2-pyridine thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone, and diphenyl thiocarbazone inhibit transformation by RSV intracellularly. Most but not all of these compounds bind to nucleic acids in the presence of copper, which may be important in their mode of action.


Interruption of oncornavirus replication by modified rifamycin antibiotics. Thirteen rifamycin SV derivatives containing 3'-alkylaminomethyl substituents fail to inhibit the activities of the simian sarcoma virus Type 1 DNA polymerase, and of cellular DNA, RNA, and poly(A) polymerases prepared from NIH Swiss mouse embryos. These compounds show a range in their toxicities for NIH Swiss mouse 3T3 cells and in their capacities to inhibit production of foci of morphologically altered cells by murine sarcoma virus (MSV). Three compounds--the N-methyl-N-hydroxyethylaminomethyl, the N,N-dimethyl-aminomethyl, and the N4-methylpiperazinomethyl rifamycin derivatives--are comparable to adenine arabinoside and ribavirin in their toxicity for 3T3 cells, but these compounds show superior focus inhibition. These compounds inhibit oncornavirus production apparently by exacerbation of a delay in growth that results from infection of 3T3 cells with MSV.


Basic aspects of calcium chemistry and membrane interaction: on the messenger role of calcium. To summarize the perspective developed in this lecture we begin by considering it as axiomatic: (1) that aqueous domains delimited by lipid membranes typify cellular structure; (2) that different compositions of extracellular and intracellular aqueous domains and differences among intracellular aqueous domains require selective permeation of lipid membranes; and (3) that inorganic ion movements across lipid membranes are a common denominator in permeation. This set of axioms lead to the following set of postulates: (1) Evolutionary solutions to the problematic apposition of ions and lipid barriers are fundamental aspects of cell function. (2) An effective messenger role for communication between aqueous domains requires (a) meticulous modulation of movement across lipid membranes and (b) selective interactions within aqueous domains. (3) An ion would be an effective messenger. In a search for an appropriate ionic messenger it is noted that inorganic cations have a wider range of interactions with biomolecules than anions, that the prevalent monovalent cations have too high a flux across lipid membranes and too weak an interaction with molecules in aqueous domains, that trivalent cations cannot as effectively be transported across lipid membranes, that divalent cation movement across lipid membranes can be well modulated and their divalent charge allows for a wide range of binding constants with biological molecules, and that for reasons of radius-compatibility with polypeptide chelation and due to the lack of stringent crystal field requirements, Ca2+ is a most suitable divalent cation for a messenger role.


Phase specific proteins in human malignant neoplasms. This is a review of the following human gene products which appear in the prenatal period, subsequently are repressed, and reappear in malignant neoplasms: alpha fetal protein; carcinoembryonic antigen; Regan's isoenzyme; fetal sulfoglycoprotein; a fetal liver ferroprotein; beta-S-fetoprotein; gamma-fetoprotein; carcinofetal glial antigen; leukemoembryonic antigens; fetal pancreatic carcinoma antigens; universally reacting oncofetal antigens; and potential oncofetal markers.


[Differential spectrophotometric method of analysing levorin in the culture broth and in the mycelium]. It was shown on model experiments that the microbiological method was not applicable for determination of levorin content in industrial intermediate products containing in addition levoristatin, since the presence of the latter made higher the results of the microbiological assay. Because of this till to the present date the quantitative content of levorin in the industrial intermediate products was determined photometrically using alcohol (pure solvent) as the reference solution. Still, this method also made higher the results of the assay, especially when the content of levorin was determined in the fermentation broth. In the solid phase levorin is contained in the mycelium which occupies only 1 to 2 per cent of the fermentation broth, while the liquid phase or the fermentation broth filtrate occupies 98 to 99 per cent. It was found that the fermentation broth filtrate contained protein admixtures which coagulated on addition of alcohol to the fermentation broth and formed fine colloid solutions. As a result the absorption values became higher. In the present study not the pure solvent but an extract of the fermentation broth filtrate containing neither levorin, nor levoristatin was used as the reference solution. Such a differential method provided elimination of all errors due to the presence of various metabolites in the fermentation broth filtrate which varied both qualitatively and quantitatively.


Associated problems of protein electrophoresis, staining and densitometry. The process of electrophoresis, a separation phenomenon, is mistakenly understood to include the sequential processes ancillary to analyte resolution, that is, staining and quantification, where the latter could be elution followed by photometry or integrating-calculating-densitometry. The theories involved in electrophoresis itself are well worked out and equally well understood but the problems which are associated with separation, chemical reaction to generate a chromogen and quantification, perhaps partly forgotten and perhaps partly ignored, are taken up and described here. They include albumin trail, resolution, unequivalent staining, prestaining and the densitometry problems associated with band widths, opacity effects and polychromaticities.


Inosiplex for localized herpes zoster in childhood cancer patients: preliminary controlled study. By multiple criteria, inosiplex-a reputed stimulator of virus-sensitized lymphocytes-had no demonstrable therapeutic effects in a preliminary controlled study of patients with localized herpes zoster and cancer. Lymphocytes from the six drug-treated patients were no more responsive to varicella-zoster antigen and phytohemagglutinin than were lymphocytes from seven patients who received a placebo.


Nursing care of the infant in surgery.

Nursing care of the infant in surgery. The operating room nurse, as an important team member, actively participates in the specialized care of the infant undergoing surgical intervention. Using the steps of the nursing process, he or she initiates the assessment preoperatively, collecting data about the health status of the patient. Based on these data, the nurse plans and prepares for the intraoperative phase and implements nursing actions while continuously and systematically reassessing the patient's condition and environment. In general, the most significant areas to consider in assessment, planning, and implementing care for infants undergoing surgical procedures are temperature regulation, fluid balance, readiness of the OR to receive the patient, prevention of infection, safe and reliable monitoring devices, careful tissue handling, and organization of priorities and interventions, especially to make efficient use of time.


Curative and palliative surgical treatment of pancreaticoduodenal adenocarcinoma. In the period 1965 to 1976 inclusive, 55 patients suffering from duodenopancreatic adenocarcinoma were surgically treated at the Free University Hospital. Twenty of these patients underwent a 'curative' Whipple pancreaticoduodenectomy for a resectable tumor. The difference in survival time makes a differentiation important between carcinomas occurring in the head of the pancreas and those of the peri-ampullary region. In our series, 11 of the former were found and 9 of the latter group. Of each group one patient died within 30 days of the operation. The average survival time of 9 patients, operated on for a tumor in the head of the pancreas, was 10.2 months, with a range from 2 to 23 months. One patient is still alive 23 months after the operation. The average survival time of 5 patients with a periampullary tumor was 22 months with a range from 6 to 52 months. Three patients are still alive, one more than 12 years and 2 more than 19 months after operation. Considering the bad results, and the fact that 30 percent of pancreatic carcinomas are multifocal, it would seem that the classical Whipple operation is a thing of the past. One can then make a plea for total pancreaticoduodenectomy or even for a regional pancreatectomy. Thirty-five patients underwent a palliative procedure, consisting of a biliary bypass combined in a number of cases with a gastroenterostomy. Five patients died within 30 days of the operation. The average survival time for the remaining patients was 9.5 months with a range of 1.5 to 30 months.


Organophosphorus pesticide poisonings in humans: determination of residues and metabolites in tissues and urine. The analyses of four organophosphorus pesticide poisoning cases, three of which resulted in death, are reported. The case histories of the subjects, along with the analysis of tissues, urine, and blood for the levels of pesticides and metabolites are given. The pesticides involved include dicrotophos, chlorpyrifos, malathion, and parathion. The methods of analysis were adapted from previously published methods that provide a very rapid means of identification of organophosphorus pesticides in the tissues or in the blood of poisoned patients.


[Infusion therapy complications in newborn and nursing infants]. The case histories of 306 babies dying at the age under 6 months were analysed. All the babies were given medicinal and nutrient solutions mainly via the subclavical veins for different diseases. In the process of the infusion therapy complications were observed which were distributed into 5 groups: 1--traumatic injuries, 2--air embolism, 3--thrombosis, 4--diffuse hyalin thrombi predominantly in the lung vessels, 5--acute renal insufficiency (ARI). Formation of the hyalin thrombi appeared to be due to the damaging effect of the administered solutions on the vascular endothelium and changes in the properties of erythrocytes and blood plasma. In the development of ARI some importance is ascribed to infusion overloading of the structurally and functionally immature kidneys of young infants.


X-ray microanalysis of 'psuedo' hyaline bodies in odontogenic cysts. X-ray microanalysis has revealed qualitative differences in the elemental composition between so-called hyaline bodies occurring in the connective tissue wall of an odontogenic cyst and hyaline bodies occurring within the epithelial lining of these cysts.


Physicochemical and immunochemical properties of carcinoembryonic antigen (CEA) from different tumour sources. The physical, chemical and immunochemical properties of carcinoembryonic antigen (CEA) purified from hepatic metastases of eight tumours, originating in the colon (6), stomach (1) and lung (1), have been examined. Differences were observed in the overall molecular charge, and also in the carbohydrate composition of the different preparations (both total % carbohydrate, and mole % of the individual sugars). Negligible differences in amino acid composition were found. Gel filtration analysis of these CEA preparations and an additional four partially purified preparations (from pancreatic, hepatic, breast and oesophageal tumour tissues) revealed a single CEA-active peak of similar molecular weight (about 200,000-300,000 daltons) in all preparations. Radioimmunoassay data for the twelve CEA preparations indicated that all preparations contain the same antigenic determinants, as detected by our antiserum, but that there are differences in the expression of these determinants in different preparations.


The effects of triton WR1339 and asialo-fetuin on the hepatic uptake of circulating native and asialo-carcinoembryonic antigen. Uptake of carcinoembryonic antigen from the circulation of the mouse is inhibited by treatment of the animal with Triton WR1339, but not by asialo-fetuin. Uptake of asialo-carcinoembryonic antigen is inhibited by asialo-fetuin, but not by Triton WR1339. These results reflect the different mechanisms of uptake of the glycoproteins. The presence or absence of sialic acid does not seem to be important in governing Kupffer-cell uptake, but when terminal galactoses are exposed on a glycoprotein, uptake by hepatocytes is preferred. Kupffer-cell uptake of carcinoembryonic antigen is not due to the formation of high-molecular-weight complexes in the blood stream. The effect of asialo-fetuin and Triton WR1339 on the biliary excretion of carcinoembryonic antigen and asialo-carcinoembryonic antigen is discussed.


Resurgence of killing and in vivo protection mediated by lymphocytes cultured from lymph nodes draining Moloney sarcomas. We have previously documented the development and subsequent disappearance of cytolytic activity mediated by lymphocytes from lymph nodes draining Moloney sarcomas destined either to regress or grow progressively. We now report that these tumour-draining lymphnode cells (LNC) that were no longer cytotoxic, spontaneously regenerated peak levels of killing after culture in vitro for 4 days in the absence of exogenous tumour antigen. Cytolytic activity, which was antigenically specific, was mediated by T lymphocytes. Resurgence of cytolytic activity in vitro was accompanied by proliferative changes (DNA synthesis, blast transformation, cell division) which peaked on the 3rd day of culture. Although normal, nonimmune LNC underwent quantitatively similar proliferative changes in culture, the killing that developed was weak and antigenically nonspecific. Transfer of cultured, tumour-draining LNC to immunologically compromised, syngeneic mice conferred complete protection from Moloney sarcoma progression. Adoptive transfer could be delayed for 6 days after tumour induction without loss of protection. These results suggest that there exists in Moloney sarcoma-bearing mice a mechanism that limits the differentiation of pre-killer cells into cytolytically active T lymphocytes, and that such inhibition is eliminated when LNC are explanted into culture.


Restricted autologous lymphocytotoxicity in lung neoplasia. Blood lymphocytes from 47 patients with lung carcinoma have been tested for cytotoxicity against cells isolated from the autologous tumour. Significant cytotoxic potential was found in 15 cases. The effectors were also tested against allogeneic tumour targets from lung and other sites. Reactions were only rarely detected (2/32 positive against lung and 1/13 positive against non-lung cells). The restriction of cytotoxicity to the autologous combination was also apparent in in vitro-generated effectors. Blood lymphocytes were co-cultivated with autologous tumour and subsequently tested against autologous or allogeneic targets. Cytotoxicity was found in 13/17 lung tumours against autologous tumour, with no reactions recorded against allogeneic tumour targets, but one case positive against the K562 cell line. These data suggest either the expression of individually distinct antigens on human pulmonary neoplasms, or the requirement for histocompatibility between target and effector in cytotoxicity reactions in man, and therefore differ from previously described patterns of lymphocytotoxicity against human tumours.


Cell-mediated immunity to encephalitogenic factor (MMI test) in women with cervical dysplasia and carcinoma in situ: the effects of serum. Lymphocyte sensitivity to encephalitogenic factor (EF) was measured with the macrophage migration inhibition (MMI) test in 60 women with dysplasia or carcinoma in situ of the cervix, in 10 women with invasive cervical carcinoma, and in 20 women with a variety of benign gynaecological conditions. Significant migration inhibition with EF (P less than 0.01) was seen with lymphocytes taken from 7/13 (54%) women with mild and/or moderate dysplasia, from 22/47 (47%) women with severe dysplasia and/or carcinoma in situ, from 6/10 (60%) women with invasive cervical carcinoma and from 3/20 (15%) women with benign gynaecological conditions. Autologous serum was seen to abrogate EF-mediated migration inhibition in 3/4 sensitized women with mild and/or moderate dysplasia, in 5/7 sensitized women with severe dysplasia and/or csrcinoma in situ and in 2/3 sensitized women with invasive cervical carcinoma. Autologous serum from 2 sensitized women with benign gynaecological conditions did not abrogate the response of their lymphocytes to EF.


Surface antigens of rat liver epithelial cells grown in medium containing foetal bovine serum. Cultured rat liver cells induced a strong antibody response in syngeneic rats, directed against foetal calf serum components which were incorporated into the liver cell surface from the cell-culture medium. This antibody could be removed by absorption with liver cells or glutaraldehyde-fixed foetal calf serum. It is possible that the antigenic cross-reactivity observed in earlier studies with cultured cells treated with carcinogens could be due to this foetal calf serum component.


Influence of hydrocortisone on the modulation of the inflammatory response. In vitro hydrocortisone, in pharmacologically attainable concentrations, binds nonspecifically to rat peritoneal mast cells and amplifies the stimulating effects of PGE1 on membrane-bound adenylate cyclase. As a consequence, the intracellular concentration of cyclic AMP in the target cells increases and histamine release is markedly reduced. Deoxycorticosterone, at the same concentrations, has no effect. These findings may in part explain the mechanism of action of anti-inflammatory steroids, possibly related to the modulating effects of E-type prostaglandins.


On the latency of tumour cells.

On the latency of tumour cells. The present experiments demonstrate that animals carrying large peripheral intramuscular tumours were free of spontaneous pulmonary metastases. Secondaries in the lung emerged, however, after administration of agents such as trypsin, 10% dextrose or antiserum to alpha-2-macroglobulin (AMG). Such metastases also appeared in animals treated with trypsin after amputation of the tumour-bearing limb. It is believed that the pulmonary vessels of tumour-bearing animals are lined with a layer of tumour-associated AMG. The presence of this peptide on vascular endothelium blocks the transmigration of tumour cells. Tumour emboli may remain dormant, i.e. unattached, in the vascular lumen. Agents inactivating AMG or enhancing vascular permeability (proteases, antisera to AMG or vasodilators) may promote the emergence of a latent tumour cell into an overt state. This is confirmed by the above experiments and by the microscopic appearance of the pulmonary vessels of test animals (shift of tumour cells from the intravascular to the perivascular space). It is suggested that latency is determined by the state of permeability of the vessels harbouring tumour emboli.


Effects of corticosteroids on the growth and metabolism of fibroblasts cultured from human skin. Hydrocortisone, betamethasone 17-valerate, clobetasone butyrate and clobetasol propionate were tested in vitro for effects on the proliferation and metabolism of six strains of fibroblasts from normal human skin. The different cell strains gave similar results: hydrocortisone and betamethasone valerate slightly enhanced growth at all concentrations (0.0001-10 microgram/ml), but high concentrations of clobetasone butyrate and clobetasol propionate significantly reduced proliferation. Secretion of acid mucopolysaccharide was most inhibited by clobetasone butyrate and clobetasol propionate, then by betamethasone valerate, with hydrocortisone having the least effect. Clobetasol propionate and betamethasone valerate at 10 microgram/ml both reduced collagen synthesis by about 50%; other protein synthesis was less affected.


The aniline blue fluorescence staining of eosinophilic granulocytes. An aniline blue fluorescence staining technique specific for eosinophils was compared to haematoxylin and eosin to determine the percentages of eosinophils in the peripheral blood of patients with atopic or with allergic contact dermatitis. The aniline blue technique proved to be excellent for demonstrating eosinophilic granulocytes. Although the eosinophilic granulocytes were reasonably demonstrable in thin layers stained with haematoxylin and eosin, the aniline blue staining seems to be better in cases of doubt. Using the same techniques the presence of eosinophil granulocytes was studied in 5 punch biopsies taken from positive patch tests (after 48 h) and 5 biopsies from positive skin reactions after and intradermal injection with an atopic allergen (after 20--30 min). In all punch biopsies taken after an intradermal injection with an atopic allergen, eosinophilic granulocytes, often numerous, were seen in the vessels of the dermis. In punch biopsies taken from positive patch tests the eosinophilic granulocytes were seen scattered through the dermis in variable numbers.


Platelet and plasma beta thromboglobulin in myeloproliferative syndromes and secondary thrombocytosis. Elevated plasma beta thromboglobulin (betatg) and decreased intracellular platelet betatg were found in patients with various myeloproliferative disorders. In secondary thrombocytosis, similar, but less marked changes were found. The abnormalities were increased during episodes of clinical thrombosis and could be suppressed in two-thirds of cases by aspirin therapy.