Experience with second marrow transplants. This report summarizes the experience with 25 patients who received a second marrow transplant. The marrow donor for the first transplant was an identical twin in four cases and a sibling matched at the major histocompatibility complex in 21 instances. The donor for the second transplant was the same as the first except for three patients whose second donor was another matched sibling. Nine patients with aplastic anemia rejected their first graft. Four of these patients were prepared for the second graft with a regimen of procarbazine and antithymocyte globulin (ATG) followed by cyclophosphamide or total body irradiation and were successfully regrafted. One rejected the second graft, two died of septicemia and one is alive and well 10 months after the second graft. Twelve patients with hematologic malignancy had a recurrence of disease after the first transplant. Despite preparation for the second graft with a variety of intensive chemotherapeutic regimens, the five patients who did not succumb to infection showed an early recurrence of disease. Four patients with hematologic malignancy had a failure of the first graft for unknown reasons, possibly related to the administration of ATG or methotrexate. One patient prepared for the second graft with procarbazine and ATG showed evidence of engraftment but died of infection. Two out of three patients given no additional preparation were successfully grafted. One died of recurrent central nervous system leukemia after 18 months and one is alive and well 26 months after the second graft.


Weak neuronal accumulation of octopamine in dopaminergic neurons of the rabbit retina. Dopaminergic retinal neurons become weakly radioactive after the injection of tritiated octopamine into the vitreous, but no other neurons do so. This indicates the absence of any effective mechanism for the accumulation of octopamine in rabbit retina.


Localization of peroxidase activity in Trypanosoma cruzi microbodies. Electron microscopic observation of Trypanosoma cruzi epimastigotes reveals the presence of microbody-like structures (microperoxisomes) in which 3,3'-diaminobenzidine (DAB) is peroxidized to electron-opaque material. The role of peroxidase in DAB peroxidation is supported by the enzyme demonstration in disrupted epimastigotes and the microbody-containing cell fractions.


Theories of enzyme specificity and their application to proteases and aminoacyl-transfer RNA synthetases. The question of enzyme specificity which is a corollary of the phenomenon of biological recognition is reviewed. The following theories are outlined briefly: non-productive binding, induced fit, transition state binding, the general strain theory and the kinetic proofreading hypothesis. Data on proteolytic enzymes and aminoacyl-tRNA synthetases are discussed in the light of predictions made by the various theories. The specificity of inhibitor and substrate binding to chymotrypsin and subtilisins is revealed at the sub-molecular level as an example of binding specificity. Kinetic specificity is experimentally distinguished from binding specificity. Conformational adaptability of enzyme and substrate, which is crucial in some theories, is documented by data on aminoacyl-tRNA synthetases. Expected and observed specificity of tRNA charging is discussed with regard to a theoretical limit of specificity. Additional means seem necessary beside those contained in the isolated enzyme-substrate system to account for the high specificity of most synthetases. In conclusion, we have arrived at quite good explanations for moderate specificity such as is displayed by many proteases, but there are still ample difficulties in the understanding of highly specific enzyme reactions.


Localization of wheat germ agglutinin receptor sites on yeast cells by scanning electron microscopy. WGA receptor sites on the surface of Saccharomyces cerevisiae cells pretreated with an alpha-mannanase were localized by gold granules labelled with WGA. The receptor sites were found on the bud scars, the mother cell-bud junction (chitin) and the bud, but not on the mother cell.


Possible significance of adverse reactions to glutamate in humans. Of those exposed to Chinese restaurant food, our studies indicate that 25% report adverse reactions (Chinese restaurant syndrome (CRS)), presumably to the mono-sodium glutamate (MSG) content. The possible significance of the symptoms is discussed in the light of the known neuroexcitatory activity of MSG. It is suggested that CRS may result from a "benign" inborn "error" of metabolism that is deserving of further study, particularly in individuals with certain other metabolic abnormalities or who are on certain types of drug therapy.


Dependence of translation on 5'-terminal methylation of mRNA. Many eukaryotic cell and viral mRNAs contain 5'-terminal m7G(5')ppp(5')N. Methylation is important for the in vitro translation of vesicular stomatitis virus and reovirus mRNAs. Unmethylated viral mRNAs are methylated by cell-free extrascts of wheat germ and L cells to form 5'-terminal structures of the type, m7GpppN and m7GpppNm, respectively. Rabbit globin mRNA also contains 5'-terminal 7-methylguanosine (m7G). Removal of the m7G by beta-elimination decreases translation. The efficient binding of mRNA to ribosomes is dependent on the presence of 5'-terminal m7G.


Genetic defects of iron transport.

Genetic defects of iron transport. Five genetic traits in man and laboratory animals have major effects on iron transport. The heterogeneous condition, hemochromatosis, in some families appears to segregate as a Mendelian trait, and is associated with defective control of intestinal iron absorption. In the very rare human autosomal recessive trait, atransferrinemia, there is an almost total lack of transferrin and gross maldistribution of iron through the body. In mice, sex-linked anemia (an X-linked recessive trait) causes iron deficiency through defective iron absorption, at the "exit" step; a similar defect probably exists in placental iron transfer. In microcytic anemia of mice, an autosomal recessive trait, iron absorption is also impaired because of a defect of iron entry into cells, which is probably generalized. Belgrade rat anemia, less understood at present, also may involve a major disorder of iron metabolism. Study of these mutations has provided new knowledge of iron metabolism and its genetic control Their phenotypic interaction with nutritional factors, especially the form and quantity of iron in the diet, may provide new insights for the study of nutrition.


Cellularity of adipose tissue in meat animals. Present information indicates that for meat animals adipocyte number is achieved most rapidly in the perirenal depot and least rapidly in the interfascicular of intramuscular depot. Adipocyte volume appears to be largest in the perirenal depot and smallest in the interfascicular and intermuscular depots. The best estimates available suggest that adipocyte hyperplasia is completed by 14 months of age in bovine animals and 5 months of age in porcine animals. However, because of certain technique limitations and the presence of many small adipocytes in very obese animals, these estimates must be considered very tentative. Studies in ovine and porcine animals indicate that early under-nutrition is not effective in reducing the number of subcutaneous and perirenal adipocytes later in life. However, the number of interfascicular adipocytes may be reduced. Several studies have demonstrated that the interfascicular adipocytes are very late developing and that adipocyte number is very important to the total quantity of intramuscular lipid.


Theoretical model of ruminant adipose tissue metabolism in relation to the whole animal. Based on theoretical considerations and experimental data, estimates of contributions of adipose tissue to energy expenditures in a lactating cow and a growing steer were developed. The estimates indicate that adipose energy expenditures range between 5 and 10% of total animal heat production dependent on productive function and diet. These energy expenditures can be partitioned among maintenance (3%), lipogenesis (1-5%) and lipolysis and triglyceride resynthesis (less thatn 1.0%). Specific sites at which acute and chronic effectors can act to produce changes in adipose function, and changes in adipose function produced by diet and during pregnancy, lactation and aging were discussed with emphasis being placed on the need for additional, definitive studies of specific interactions among pregnancy, diet, age, lactation and growth in producing ruminants.


Uterine skin grafts and fertility control in the rat. Autologous intrauterine skin grafting was studied as a method of fertility control in the rat. Skin taken from the ear was grafted onto the right horn in 52 rats. All skin grafts "took" and developed into one of three forms: (1) replacement of endometrium over a wide area, (2) polypoid formations, or (3) skin bridges. Curettage before the skin grafting did not affect the "take" or subsequent course of the graft. After mating, no pregnancy occurred in skin-grafted horns, whereas control horns behaved like those in control rats. Results obtained in rat uteri indicate another approach to the treatment of uterine bleeding and possibly to contraception.


[Clinical application of synthetic LH-RH for anovular women unresponsive to clomiphene therapy (author's transl)]. The purpose of this study is to clarify the significance of synthetic LH-RH (RH) as a therapeutic agent in the treatment of anovular women who fail to respond to clomiphene therapy. Fifteen women with hypofunction of the hypothalamus-pituitary system who were given the RH-test were divided into two groups according to the maximum increased level of LH shown by each. Group I consisting of 7 women who showed increased levels of over 20miu/ml received a combination of clomid+estrogen+RH(C.E.R). Blood levels of LH, FSH and estradiol were measured in each. Group II consisting of 8 women who showed maximum levels of LH below 20 miu/ml received RH intramuscularly, 100 mug per day for 20 to 30 days (referred to as RH treatment). The RH-test was performed in this group before treatment, and 1, 7 and 21 days after treatment. Blood levels of estradiol were also determined before, during and after treatment. 1) Ovulation occurred in 5 of the 7 women in group 1 and 3 became pregnant. The LH surge was prolonged and hormonal secretion increased with administration of C.E.R.. The normal estrogen surge and gonadotropin surge occurring in the ovulatory cycle were thus produced artificially. Since administration of clomiphene alone tends to produce insufficiency of cervical mucus secretion because of its anti-estrogen effect, the addition of estrogen to the combination of C.E.R. probably increases the cervical secretion of mucus and enhances the probability of impregnation. 2) Compared to pretreatment levels, RH treatment clearly increased the pituitary secretion of LH and FSH. Even 3 weeks after RH treatment, the pituitary secretion of gonadotropin was definitely higher than before treatment. Fluctuations in blood levels of estradiol during and after treatment were not significantly different than before treatment. These observations would suggest that prolonged administration of RH enhances the gonadotropic function of the pituitary, not only in the secretion of the hormones but also in the synthesis of gonadotropin. Judging from the insignificant effect on the blood level of estradiol, it would appear that RH itself possesses the ability to produce gonadotropin.


Urbanization and de-urbanization of the black population before the Civil War. Pre-Civil War black urbanization is examined using data from federal census records, 1790 to 1860. The black population is found to be as urban as the white population initially, but its urbanization underwent relative decline in the last two decades before the Civil War. Foreshadowing current patterns, the northern black population was heavily concentrated in the largest cities, and the free black population was the most urban of all groups. The timing of black urban decline in the North, as well as regional and size of place differences in that decline, suggest that both competition with immigrants in major eastern seaboard cities and the passage of the Fugitive Slave Law in 1850 contributed to black de-urbanization. For the South, the explanations of black urban decline proposed by Wade, Conrad and Meyer, Goldin, and Bonacich are evaluated, and Bonacich's split labor market theory is judged to be most consistent with the demographic trends.


Pemphigus-like antibodies in dermatitis herpetiformis. Pemphigus-like antibodies were demonstrated in a patient with dermatitis herpetiformis. The patient was a 28-year-old Japanese who showed itchy tense bullae on the back, chest and shoulders. We speculate the antibodies are similar to those found in burns, drug eruptions and certain other skin diseases.


Topical corticosteroid therapy and its effect on the hypothalamic-pituitary-adrenal axis. All clinically effective topical corticosteroids have the potential for suppressing the pitutary-adrenal axis if large amounts are applied under occlusion on extensive areas. Recovery of the axis function occurs rapidly. In children, however, the risk of chronic suppression of the adrenal axis function with impairment of growth after topical treatment with potent steroids is a real one. Potent steroids in children should, therefore, only be used on refractory areas with carefully controlled quantities.


Clinical trial comparing hydrocortisone 17-butyrate to betamethasone 17-valerate in a series of patients with eczematous skin diseases. A randomized, double-blind, left-right comparative study was carried out to compare the value of hydrocortisone 17-butyrate with that of betamethasone 17-valerate in the treatment of eczematous skin disorders. In a series of 23 patients with such disorders, no differences between the two preparations was demonstrated with regard to effectiveness.


Clinical experiences with hydrocortisone 17-butyrate. In a double-blind comparative study, by 29 dermatological departments, the activity of hydrocortisone 17-butyrate (HC 17-B, Locoid), triamcinolone acetonide (TA) 0.1% and hydrocortisone 21-acetate (HA) 1%, were compared in patients suffering from acute eczematous dermatitis, atopic dematitis and psoriasis. After a 7-day period of observation, the results were evaluated by means of a chi2 test, and an Armitage tests. The following results were obtained: in acute eczematous dermatitis HC 17-B was found to be superior to the placebo and equal to TA; in atopic dermatitis HC 17-B was found to be superior to the placebo and HA,  equal to TA; in psoriasis vulgaris HC 17-B was found to be superior to the placebo, HA and TA.


Efficacy of a live oral cholera vaccine in human volunteers. A live attenuated oral cholera vaccine has  been given to volunteers with complete safety. The vaccine strain appeared to multiply significantly in intestinal contents and to result in appreciable vibriocidal antibody response. Subsequent challenge with virulent Inaba vibrios demonstrated substantial protection from clinical illness and from  vibrio shedding. The possibility of reversion to toxin production is discussed.


LH-RH-dependent synthesis of protein necessary for LH release from rat pituitary glands in vitro. Anterior pituitary glands of intact diestrous and gonadectomized female rats were incubated with a supramaximally active dose of LH-RH. Puromycin (P) and cycloheximide (C) did not consistently affect the LH release from glands of ovariectomized rats. In intact rats, LH release induced by LH-RH occurred in two phases, an initial one (relatively slow rate of release) and a secondary one (high rate of release). P and C had no effect on the initial phase, but prevented the secondary one. Pre-incubation with LH-RH prevented the effect of P and C added after 4 hours. Since P and C did not affect the total amount of LH present in media and hypophyses, the LH-released during the P- and C-sensitive phase is not newly formed LH. It is concluded that LH-RH induces the synthesis of protein which is necessary for LH-RH-induced LH release. The initial phase of LH release is made possible by protein already present in the glands at the beginning of the experiment.


Compared efficiency of a killed vaccine of Salmonella typhimurium, a live vaccine and an antigenic fraction in oral immunization of mice. In an attempt to determine the best method of immunizing mice by oral route against Salmonella typhimurium, the animals were vaccinated by means of a killed-pathogenic strain, an avirulent mutant of the same bacteria, and a protective antigen removed from the supernatant culture of this mutant. After changing doses of vaccines and the interval between vaccination and challenge, the results obtained show the superiority of the live vaccine and protective antigen with regard to the killed one. Under our experimental conditions enteral vaccination appears to be more effective than the parenteral one.


Criteria in the evaluation of live intranasal influenza virus vaccines. Live influenza virus vaccines should meet the following criteria: attenuation, immunogenicity, lack of spread, genetic stability, production in a suitable cell substrate, and  stability during storage. In addition, they should be able to induce a wide antigenic protection. These various aspects will be discussed with reference to the "Alice" strain of live influenza A virus, which possesses all the properties for a good live attenuated virus vaccine.


Experience of nasal application of inactivated influenza vaccine. The present experiment shows the efficacity of the sesame-oil adjuvant influenza vaccine. The plain inactivated vaccine merely shows a tendency towards effectiveness and only in a field study was a statistically significant effectiveness observed. We had hitherto made such a field experiment in which the plain inactivated influenza vaccine showed much more effective values. It is not clear that in the present experiment such a result was obtained.  The efficacy of intranasal application of inactivated influenza vaccine seemed to be fairly good and appeared quite soon after spraying, although its effect lasted no more than one month.


Antagonistic activity of analogs of luteinizing hormone-releasing hormone (LH-RH) in vitro. The ability of eighteen analogs of LH-RH to inhibit LH-RH-induced LH release was tested in primary cultures of rat anterior pituitary cells. [Des-His2]LH-RH, [Des-His2, D-Leu6]LH-RH and [Des-His2, D-Phe6]LH-RH inhibited 50% of LH-RH-induced LH release at molar ratios (MR50S) of 3000, 500 and 60, respectively, while [D-Phe2]LH-RH, [D-Phe2, D-Leu6]LH-RH and [D-Phe2, D-Phe6]LH-RH had similar effects at MR50S of 1000, 150 and 25, respectively. This indicates that substitution of D-phenylalanine for histidine at position 2 of LH-RH leads to compounds approximately 3-fold more potent than the corresponding [Des-His2]-analogs. [D-Phe2, D-Phe6]LH-RH, the most potent antagonist tested has however a slight agonistic activity (0.003% that of LH-RH itself). [D-Phe2, D-Phe6, Phe7]LH-RH, [D-Phe2, Phe3, D-Phe6]-LH-RH and [D-Phe2, Phe5, D-Phe6]LH-RH inhibit 50% of LH-RH action at MR50S of 400, 100 and 75, respectively. All of the analogs mentioned in the last group have LH-releasing activities below 1/100,000 that of LH-RH itself.


Clinical evaluation of neuraminidase monospecific (HEqN2) recombinant influenza vaccine in children. Phased clinical trials were undertaken to evaluate the efficacy of neuraminidase specific recombinant (HEqN2) inactivated influenza vaccine in a population of school children. Groups of subjects were immunized under code, with influenza A2 Port Chalmer (H3N2), Port Chalmer neuraminidase recombinant (HEqN2), and placebo vaccines (vaccine diluent) before the onset of A2 strain influenza epidemic in this population. Preliminary results have provided the following information. Immunization with commercial Port Chalmer (H3N2) or neuraminidase recombinant influenza A2 (HEqN2) vaccines, in a childhood population was safe and without any major adverse effects. Vaccination with H3N2 vaccine regularly induced seronconversion for specific hemagglutination-inhibiting (HAI) antibodies in over 60% of vaccinated subjects. The mean titers of antineuraminidase antibody (ANAB) in H3N2 recipients who were seropositive prior to immunization increased five-fold while the ANAB titers of individuals who were seronegative prior to immunization did not rise significantly after immunization. On the other hand, immunization with HEqN2 vaccine resulted in little or no HAI response against H3, while specific ANAB response was observed in over 70% of such vaccines. The ANAB titers increased approximately 10 fold in the vaccines who were seropositive prior to immunization, and the titers in subjects seronegative prior to immunization were 5-6 fold higher than the post immunization titers observed in seronegative individuals in the H3N2 vaccinated group. Preliminary data on protection against natural reinfection suggested that, although the incidence of serological reinfection was similar in all vaccine groups, the expression of clinical disease was somewhat milder in HEqN2 vaccinees and in individuals with high levels of ANAB. These studies provide tentative support to the potential use of neuraminidase specific vaccine for mass immunoprophylaxis against influenza A2 virus.


Compartmentalization and movement of calcium in the thyroid. The present work suggests that in dog thyroid tissue Ca2+ is distributed at least in two compartments (A) and (B). Compartment (A) could be the extracellular space, and extracellular binding sites for Ca2+. The uptake of Ca2+ in this compartment is increased and the release is decreased at 0 degrees C. The release is not influenced by the ionophore A23187 or by metabolic inhibitors (NaF, iodoacetate, dinitrophenol) or by thyrotropin (TSH). Compartment (B) is defined functionally as a slowly exchangeable store of Ca2+. Uptake and release from this compartment are temperature dependent. The release is accelerated by A23187 and by antimycin A, this suggests an intracellular, presumably mitochondrial, location. TSH stimulates the efflux of Ca2+ originating from the cellular compartment (B). Our data are compatible with the hypothesis that, as in other tissues, the translocations of stored intracellular calcium may be a crucial step in the activation of the thyroid cell.


Immunization of man and animals against influenza by oral and intranasal routes. Live human and equine influenza virus strains modified by serial passage on allantois-on-shell system (AOS) in the presence of normal horse serum were administered orally or intranasally to volunteers or horses. Mostly mild clinical short-lasting reactions, replication in nasal mucosae, transmission to placebo recipients and significant local or circulating antibody rises were observed following administration to volunteers of strains modified by five or less serial passages on AOS in the  presence of normal horse serum (NHS). Milder clinical reactions, no replication, no viral transmission and lower immunogenicity were observed when up to ten serial passages on AOS+ NHS were carried out. Similar results were observed in horses and colts. Heavy shedding of A/Eq-2 strain following the challenge was observed in placebo recipients. Colts immunized intranasally were completely protected while 33% of those immunized orally shedded small quantities of A/Eq-1 and A/Eq-2 viruses. However, a sharp rise of local antibodies against both strains was measured two days after the challenge in the three groups.


The use of live attenuated influenza vaccine ts-1(E) in man. Live temperature-sensitive influenza virus vaccines were tested in two volunteer experiments. The vaccine virus was originally derived from a temperature-sensitive mutant of influenza A/Great Lakes/1965 (H2N2) produced by chemical mutagenesis with 5-fluorouracil. The ts lesions of this strain were subsequently transferred (HI) antibody. Only 9 men (13%) were infected, presumably as a result of over-attenuation of the virus and/or insufficient titer of the inoculum. In the second experiment (1974), 20 young adults were given 0.5 ml per nostril of vaccine containing a recombinant of influenza A/Udorn/307/72 clone 24 (10(5.5) TCID50/ml) with an in vitro shutoff temperature of 38 degree C. Virus was shed by seven volunteers (maximum titer, 10(2.5)TCID50/ml). None of 21 isolates contained revertant wild type virus. Serum HI and antieuraminidase (NI) and nasal wash neutralizing antibody responses occurred in 11 (55%), 7 (35%), and 8 (40%) volunteers, respectively. Post-vaccination serum HI and NI and nasal  neutralizing antibody geometric mean titers were 3.0, 9.4, and 1.7 lob2, respectively. Seven volunteers judged they had colds (symptom scores 4-32). Rhinitis and mild pharyngeal discomfort were the only consistent complaints and fever was absent. The findings in the latter trial will be compared with results of volunteer experiments with Udorn/72 ts-1-(E) in other laboratories and to studies with standard inactivated influenza vaccines given parenterally.


Use of an inhibitor-resistant live attenuated influenza vaccine in normal and asthmatic adults. The efficacy of a monovalent live attenuated influenza A (H3N2) vaccine (an inhibitor-resistant recombinant strain named "Alice") and of a bivalent vaccine composed of "Alice" and influenza B strain R75 (also inhibitor-resistant), was tested in healthy and asthmatic adults. Two intranasal doses of the monovalent "Alice" vaccine were given to 95 healthy adults in the winter of 1973-74. Ninety-three % of 68 subjects with initial serum hemagglutination (HI) titers of less than or equal to 1:40 had a significant (4-fold or greater) antibody increase in post-vaccination sera. Overall, 77% of the vaccinees had significant antibody rises. Two doses of the bivalent (A/B) vaccine were given to 53 healthy adults in the winter of 1974-75. Eighty-two % of 34 subjects with initial HI titers of less than or equal to 1:40 had 4-fold or greater antibody rises to influenza A, and overall 57% of the vaccinees responded. The B component of the bivalent vaccine was less effective; only 56% of persons with initial HI titers of less than or equal to 1:40, and 28% of all vaccinees had significant antibody rises. Both tf asthmatics who received "Alice" and one of 10 (10%) who received the bivalent vaccine had serologic responses to influenza A. None of the asthmatics responded to the B component of the bivalent vaccine. Analysis of the incidence of febrile respiratory illness during an influenza outbreak in the winter of 1974-75 revealed no differences in the attack rates of placebos and vaccines. In conclusion, both the "Alice" and bivalnet (A/B) vaccines were effective in eliciting serologic responses to influenza A in healthy persons. They were less effective in asthmatics. The lack of protection observed may have been due to the onset of influenza before the vaccine could take effect or to the failure of the vaccine itself.


Vaccination by non-parenteral routes: characteristics of immune response. Antibody and cell-mediated immune response in systemic  and external mucosal sites was studied after natural or vaccine induced infections with rubella and mumps viruses. Natural rubella infection or immunization with RA27/3 rubella vaccine by intranasal and frequently by the subcutaneous route resulted in regular appearance of antibody response in the serum and respiratory tract and cellular immunity in circulating lymphocytes and tonsillar lymphoid tissue. Subcutaneous immunization with HPV-77 and Cendehill rubella vaccine resulted in antibody response in the serum with little or no response in the respiratory tract. A minimal cell-mediated immune response in systemic or respiratory lymphoid tissue was observed after such immunization. Intranasal immunization with HPV-77 frequently elicited a transient antibody and cell-mediated activity in the respiratory tract with no response in the serum and peripheral lymphocytes. Studies carried out with natural mumps infection or subcutaneous immunization with live attenuated mumps vaccine suggested that either route of infection may result in the development of antibody and cell-mediated immune responses in systemic sites as well as in the respiratory tract. These observations suggest that the immunologic outcome of  immunization by non-parenteral route may be determined by the types of viral antigen employed, the nature of locally available immuno-competent tissue, the ability of mucosal site to capture an antigen or accept replication of live virus vaccines, and the degree of prior sensitization with the same antigen.


Natural challenge of subjects vaccinated with WRL 105 strain live influenza vaccine in a residential community. In the spring of 1975 an outbreak of influenza associated with influenza virus A/Scotland/840/74 virus occurred in a residential college where the previous autumn some students had been immunised with a single intranasal dose of Recombinant WRL 105 (H3N2) (A/Okuda/57xA/Finland/4/74) strain live attenuated infleunza virus vaccine. During the outbreak none of seven students who had been vaccinated suffered from influenza but an influenzal illness did occur in four of eleven who had received placebo nose drops only. Fourfold or greater increases in hemagglutinating inhibiting antibodies between sera collected three weeks after vaccination and those collected three months later following the influenza epidemic were found in one of seven vaccinated and in  nine of eleven placebo treated subjects and also in one student who had received neither  vaccine nor placebo; a difference in serological response which is statistically significant (p less than 0.01). Thus recombinant WRL 105 live attenuated vaccine was found to have conferred substantial protection against a current wild strain of influenza A virus without causing any appreciable untoward reactions.


A clinical trial of WRL 105 strain live attenuated influenza vaccine comparing four methods of intranasal vaccination. A single intranasal dose of 10(7.0)EID50 recombinant WRL 105 strain live attenuated influenza vaccine was administered intranasally to 193 volunteers either as nose drops or by one of three spray devices which produced sprays of differing physical characteristics. In volunteers with homologous hemagglutinating inhibiting antibody titres of less than or equal to 20 before vaccination, seroconversion rates varied widely from 80% following the administration of drops to 71%, 57% and 28% with each of the spray devices. In the week following vaccination 16 (22%) of 74 volunteers who were found to show a fourfold or greater antibody response took analgesics to control symptoms in comparison with 4 (7%) of 58 volunteers who exhibited no serological response to vaccination (p less than 0.05). However, neither of the occurrence of  upper respiratory nor systemic symptoms were significantly different in these two groups and the level of attenuation of the recombinant WRL 105 strain appears to be acceptable for future use.


Clinical trials with intranasally administered WRL 105 strain live influenza vaccine in volunteers. The results of clinical trials carried out  with WRL 105 strain live influenza vaccine are reviewed. These studies aim to assess the immunogenicity and reactivity of the strain and its propensity for transmission to unvaccinated contacts. The advantages of one and two dose schedules are discussed.


Preliminary results of oral influenza vaccination with live attenuated viruses. 151 subjects, vaccinated by oral route with live influenza viruses attenuated in the USSR (bivalent  A/England/42/72-B/Hong Kong/5/72 vaccine) and 66 non-vaccinated cohabitants have been studied. The vaccination did not cause any important side effect. The vaccine showed good immunizing activity: HI antibodies appeared in 91% of the subjects initially devoid of antibodies against A type and in 70% against B type. No viral diffusion occurred from the vaccinated to the cohabitants. During an A/Port Chalmers/1/73 epidemic the morbidity (3.3%) among the orally vaccinated patients turned out significantly lower than that among the non-vaccinated cohabitants (12.1%). The protection index was 72.6%.


Clinical trials carried out to assess non-parenteral routes for administration of Wistar RA 27/3 strain live attenuated rubella vaccine. The problems encountered in obtaining acceptable seroconversion rates following intranasal and buccal administration of Wistar RA 27/3 strain live attenuated rubella vaccine are discussed with reference to vaccination technique, virus dose and other factors. Results from buccal administration of vaccine were not encouraging. However, intranasal vaccination may be acceptable if devices can be developed for the administration of vaccine which give reproducible sero-conversion rates equivalent to those obtained by subcutaneous vaccination.


Antigenicity testing of inactivated oral enteric bacterial vaccines for human use. This study deals with the laboratory testing of the antigenicity of inactivated oral enteric bacterial vaccines for human use, viz. typhoid, dysentery, Escherichia coli and cholera vaccines. For the assays the following methods are applied : 1) various types of active mouse protection tests 2) serum and coproantibody determinations in immunized persons and experimental animals, 3) protective ability of the immune sera in mice and embryonated eggs, 4) hemolytic and bacteriolytic plaque assays. It is pointed out that the most important question: how far the results of these tests are in agreement with the degree of efficacy of vaccines in man, requires to be clarified.


Vaccination against typhoid fever with a live oral vaccine. A Salmonella typhi gal E mutant, designated Ty 21a, has been developed on the basis of virulence and protection  studies with similar Salmonella typhimurium mutants in mice. Gal E mutants are characterized by a block in the enzyme UDP-4-galactose-epimerase. They owe their outstanding immunizing capacity when used in live oral vaccine to the fact that when galactose is supplied exogenously, as occurs in vivo, wild-type cell wall structures are synthesized. On the other hand, avirulence of these mutants is based upon the fact that when galactose is taken up it is partly accumulated as galactose-1-phosphate and UDP-galactose, which induces lysis of the bacteria. Strain S. typhi Ty 21a does not revert to wild type in vivo and in vitro. Its safety for man has been demonstrated in studies involving 137 adults and 370 children. S. typhi Ty 21a also has been shown to protect against challenge with virulent S. typhi in human volunteers.


Efficacy of a live oral typhoid vaccine in human volunteers. A live oral attenuated vaccine, lacking the enzyme epimerase, has been given with complete safety to 173 men. Two preparations of the vaccine, one with and one without galactose in the initial culture media, led to somewhat differing results. Vaccine A, prepared with galactose, was more readily identified in the stool specimens of its recipients and was more likely to provoke an O antibody response than was vaccine B. Furthermore, the clinical protection from typhoid fever was significant in the vaccine A group, whereas not so with the vaccine B counterpart. The protection afforded by vaccine A exceeds that of any of our previous candidate strains. It is perhaps not presumptuous to imagine that such a vaccine would be equally effective in an area endemic for typhoid fever, where the vaccine might act as a booster effect in a previously exposed population. Remaining questions to be answered include the duration of the protection, and the efficacy of a lyophilized preparation.


Controlled field  trials of three different oral killed typhoid vaccines in India. Three vaccination trials against typhoid fever  were carried out in 1968/69, 1970/71 and 1974 in New Dehli. The vaccine was generally administered in tablet form  on three consecutive days. Each new trial consisted of a larger number of killed bacteria: 100.10(9), then 300.10(9) and finally 400.10(9) killed S. typhi. The placebo and vaccinated groups were composed of 6,000 to 7,000 persons, sometimes only  children from 6 to 17 years. The number of typhoid fever cases which appeared under normal conditions of infection did not show significant difference between the vaccinated and non-vaccinated subjects during the 18 month  period of observation.


The split-brain neonate: a surgical method for corpus callosum section in newborn kittens. One way to determine the importance of interhemispheric interaction in the development of adaptive and acquired behavior is to section completely the corpus callosum about the time of birth before myelination commences and before any significant hemispheric interaction takes place. Therefore, we developed a technique for commissurotomy in the neonatal kitten 36 to 72 hr of age. A specially designed "commissurotomy knife" was used which eliminated retraction of the hemispheres. Histology showed completeness of corpus callosum section as well as commissure of the fornix without any apparent damage to cortical or subcortical structures. This technique meets the following criteria: (1) reproducibility or lesions without additional nonspecific damage; (2)minimal exposure and manipulation of the delicate newborn brain: (3) brief operational procedure minimizing risk of infection; and (4) low mortality rate.


Stimulation of glucagon secretion by scorpion toxin in the perfused rat pancreas. Toxin from the scorpion Leiurus quinquestriatus was used to release norepinephrine from sympathetic nerve endings in the perfused rat pancrease. Addition of toxin, 10 mug./ml., to perfusate containing 0.3 mg./ml. glucose caused a large increase in release of norepinephrine and glucagon. Glucagon secretion was suppressed by perfusate containing 3.0 mg./ml. glucose but still responded to stimulation with scorpion toxin. Atropine, 10 muM, had no effect on either norepinephrine or glucagon release in response to scorpion toxin. The release of glucagon was blocked by 100 muM propranolol, 10 muM phentolamine, or 30 muM phenoxybenzamine. Somatostatin, 55nM, did not affect the release of norepinephrine by scorpion toxin but totally inhibited the glucagon response. These results suggest that pharmacologic stimulation of the adrenergic nerve endings in the rat pancreas can elicit a rapid release of glucagon. This response can be prevented by appropriate concentrations of either alpha or beta adrenergic blocking agents or somatostatin.


Comparison of peripheral and portal routes of insulin infusion by a computer-controlled insulin infusion system (artificial endocrine pancreas). This study was undertaken to determine the different consequences of portal and peripheral routes of insulin administration by the artificial endocrine pancreas. Intraportal glucose was infused (10 mg./min./kg. for 60 minutes) in anesthetized normal and pancreatectomized dogs while blood glucose concentrations were monitored continuously. During computer-controlled insulin administration normal glucose tolerance was restored by both portal and peripheral routes of insulin delivery. There were also no significant differences in (1) glycemic patterns, (2) insulin infusion patterns, (3) peripheral IRI levels, and (4) total insulin requirements between the two routes. It is apparent that the peripheral route, which is more readily accessible than the portal route, may be an appropriate infusion site for an implantable or portable prosthesis for controlling blood glucose concentration.


Immunopathology of renal extracellular membranes in diabetes mellitus. Specificity of tubular basement-membrane immunofluorescence. This study documents the presence of marked immunofluorescence for IgG and albumin in renal extracellular membranes, especially tubular basement membranes (TBM), of patients with severe diabetic nephropathy. A comprehensive immunofluorescent analysis was carried out on kidney tissue from 83 patients--Group I: 24 living normal renal allograft donors and two infants less than one week of age. Group II: 24 patients with severe nephropathy who had juvenile onset of diabetes 16 to 30 years previously and who ranged in age from 20 to 47 years. Group III: 33 patients with severe kidney disease of varied etiologies with an age range of five to 63 years. The sections were assayed for a variety of proteins (immunoglobulins, complement components, and tissue antigens). Kidney sections of all patients with severe diabetic nephropathy were readily distinguished from kidneys of other patients and normals by the intense linear staining of the extracellular membranes, especially the tubular basement membrane for IgG and and albumin. Dual-labeled studies using FITC anti-basement membrane (BM) and tetramethyl rhodamine (TMR) antialbumin demonstrated localization of the albumin predominantly to the outer but also the inner TBM while the BM antisera reacted more intensely with the inner membrane. There is no evidence that an immunologic process is responsible for these findings. These immunofluorescent findings are specific for severe diabetic nephropathy and may reflect structural changes in the renal extracellular membranes that permit entrapment of serum proteins, possibly due to changes in permeability.


Immunopathology of renal extracellular membranes in kidneys transplanted into patients with diabetes mellitus. Kidneys of patients with severe diabetic nephropathy demonstrate marked linear immunofluorescent staining of extracellular membranes, including the tubular and glomerular basement membranes (TBM and GBM) and Bowman's capsule. Immunofluorescent studies were carried out on kidney tissue obtained from 12 diabetic and 17 nondiabetic patients from two to 12 years following renal transplantation. The frequency and intensity of SgG and albumin staining of these membranes were significantly greater in the diabetic than in the nondiabetic patients (P less than 0.0005). TBM, GBM, and Bowman's capsule staining did not occur in any of the seven kidneys studies at the time of their transplantation into diabetic recipients. Thus, the abnormalities leading to the deposition or trapping of proteins in renal extracellular membranes occur early after the placement of normal kidneys into the abnormal metabolic environment of the diabetic transplant recipient. The present study supports the concept that basement membrane alterations in diabetes are a consequence of the biochemical perturbations of diabetes rather than a separately inherited genetically linked disorder.


Glucagon release precedes insulin release in response to common secretagogues. The dynamics and interrelationships of glucagon and insulin secretion were studied in the isolated perfused rat pancreas by utilizing a series of compounds that stimulate the release of both hormone. Leucine, arginine, prostaglandins F2alpha and E2, bovine growth hormone, and isoproterenol were administered individually over 60-second intervals. The release of glucagon preceded that of insulin in response to all compounds tested. The rapidity of glucagon release varied in response to different secretagogues; the time course of insulin release was fairly constant. The timing and the magnitude of glucagon and insulin release did not correlate statistically. (1) pancreatic alpha cells respond more rapidly than beta cells to the same stimulus; (2) antecedent release of glucagon is not the principal mediator of insulin release in response to stimuli common to both hormones; and (3) endogenous glucagon may at best modify the release of insulin evoked by certain secretagogues.


Major central nervous system malformations notified in Northern Ireland, 1969 to 1973. In Northern Ireland, during the years 1969 to 1973, there were 485 notifications of anencephalus, 525 of spina bifida and 328 of hydrocephalus in a population of 157,725 (live and still) births. The data were based on the voluntary notification system for congenital malformations which has been operating in Northern Ireland and in England and Wales sine 1964. The malformation rates per 1000 (live and still) births were 3-1 for anencephalus, 3-3 for spina bifida and 2-1 for hydrocephalus. Secular trends in these data indicate a decrease in the incidence of all three major central nervous system malformations, but this is significant only in relation to anencephalus. Spina bifida was more common in female births than in male births, and 79 per cent of affected infants were liveborn. Indirect evidence suggests that some 40 per cent of the total number of live and stillborn infants having spina bifida at birth will survive to one year of age.


Comparison of natural and synthetic prostaglandins on gastric and pancreatic secretions and peptic ulcer formation in conscious cats. In conscious cats with chronic gastric and pancreatic fistulas, the natural prostaglandins (PGs) of the E (PGE1 and PGE2) and F (PGF1 alpha and PGF2 alpha) series and synthetic 15-methyl analog of PGE2, 15(S) 15-methyl-PGE2 methylester were compared with regard to their action on gastric and pancreatic secretions and peptic ulcer formation. This study indicates that in comparison with natural PGs, the synthetic 15-methyl analog of PGE, is a more potent inhibitor of gastric secretion regardless of the route of administration and the mode of gastric stimulation.  It more effectively prevents the formation of peptic ulcers in conscious cats.


A fraction isolated from porcine upper small intestine stimulating pepsin secretion in the cat. The preliminary purification of a material, apparently distinct from any hitherto isolated gastrointestinal hormone, with pepsin release stimulating activity in the cat is described. This material has shown no inhibitory effect on pentagastrin-stimulated secretion of acid, no effect of its own on gastric acid secretion and antral motility, and only a weak stimulatory effect on pancreatic secretion of bicarbonate.


Lactoferrin in human pancreas. Immunohistological localization in normal and pathological pancreatic tissues. The protein composition of normal human pancreatic juice and pancreatic juice of men with chronic calcifying pancreatitis (CCP) were compared using immuno-diffusion techniques. An additional protein was found in pathological pancreatic juice and this protein has been identified as lactoferrin. Its concentration has been determined. The indirect immunofluorescence method was used to detect and localize lactoferrin in 9 samples of human pancreas from 3 patients with CCP and 6 patients without CCP. The fluorescence was found in all samples. Lactoferrin staining was localized in lumen acinar and in the cytoplasm of the acinar cells. The fluorescence was stronger in the apical zone of acinar cells. When lactoferrin antiserum was incubated with lactoferrin insolubilized by glutaraldehyde, no fluorescence staining was detected. The differences between our results obtained by immunodiffusion and immunofluorescence techniques are explained by the different sensitivity of the two techniques and these results indicate that lactoferrin is a protein of pancreatic secretion.


Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol, Nuran). The tricyclic compound cyproheptadine (Periactinol, Nuran) inhibited glucose-induced insulin release from the perfused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of 14C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.


Pancreatic polypeptide - a postulated new hormone: identification of its cellular storage site by light and electron microscopic immunocytochemistry. A peptide, referred to as pancreatic polypeptide (PP), has recently been isolated from the pancreas of chicken and of several mammals. PP is thought to be a pancreatic hormone. By the use of specific antisera we have demonstrated PP immunoreactivity in the pancreas of a number of mammals. The immunoreactivity was localized to a population of endocrine cells, distinct from the A, B and D cells. In most species the PP cells occurred in islets as well as in exocrine parenchyma; they often predominated in the pancreatic portion adjacent to the duodenum. In opossum and dog, PP cells were found also in the gastric mucosa. In opossum, the PP cells displayed formaldehyde - induced fluorescence typical of dopamine, whereas no formaldehyde-induced fluorescence was detected in the PP cells of mouse, rat and guinea pig. Also in these latter species, however, PP cells appear to possess amine-handling properties, a feature common to many peptide hormone-producing cells. The ultrastructure of the PP cells was defined by combining immunohistochemistry of semi-thin plastic sections with electron microscopy of adjacent ultrathin sections. PP cells show the ultrastructural features of peptide hormone-secreting cells. The PP cells of cat and dog contain fairly large, rather electron-lucent granules, and are probably identical with the previously described F cells. The PP cells of rat, guinea-pig, chinchilla and man contain small, fairly electron-dense granules. In these latter species no F cells are found. By immunoperoxidase staining of ultrathin sections, the PP immunoreactivity was found to be localized to the cytoplasmic granules. These observations provide support for the view that PP is a true pancreatic hormone.


Effects of sulfonylureas on histochemical and ultracytochemical calcium distribution in B-cells of mice. The study examines the effects of sulfonylurea compounds on the histo- and ultracytochemical calcium distribution within the B-cells of mice using the glyoxal-bis-(2-hydroxyanil) (GBHA) and the pyroantimonate method combined with X-ray microanalysis. Treatment with tolbutamide (200 mg/kg), glibenclamide (2 mg/kg) and glisoxepide (2 mg/kg), causing moderate hypoglycemia and B-cell degranulation, was associated with an unchanged (30, 90 min) or slightly increased (180, 360 min, 4, 42d) GGHA staining intensity of the islet cells compared with controls. Ultra-cytochemically sulfonylureas provoked, compared with controls, a redistribution of calcium-rich, electron dense pyroantimonate precipitates (EDPP). Precipitation predominantly occurred along the inner surface of the plasma membranes and within the granule halos. In contrast, the cytoplasmic matrix, the Golgi complexes and the rough endoplasmic reticulum contained only few fine precipitates. The sulfonylureas investigated exerted identical effects on the histo- and ultracytochemical calcium distribution in B-cells. The results indicate that sulfonylurea-induced insulin secretion is associated with an accumulation and redistribution of calcium within the B-cells. This supports the hypothesis that an altered calcium handling by the B-cell mainly accounts for the insulinotropic effect of sulfonylureas.


The comparative effects of barbituric acid phenobarbital on blood glucose and insulin secretion in mice. The effects of barbituric acid and phenobarbital upon carbohydrate metabolism in mice were compared. An intraperitoneal dose of 100 mg/kg of barbituric acid increased blood glucose concentrations during an intravenous glucose tolerance test, but did not alter the rate of glucose disappearance from the blood. Barbituric acid also antagonized the hypoglycemic effect of intravenously administered tolbutamide. The same dose of phenobarbital had no effect. An in vitro concentration of 100 mug/ml of barbituric acid decreased the responsiveness of isolated mouse pancreatic islets to glucose stimulation (3.0 mg/ml D-glucose). Again phenobarbital, 100 mug/ml, was without effect. The structural similarities between barbituric acid, tolbutamide and alloxan suggest that the effects observed in these experiments might reflect a competition for binding to reactive sites on or within the pancreatic B-cell.


[Clinical experinece using tubular grafts in the reconstruction of the right ventricular outflow tract (author's transl)]. Conduit reconstruction of the right ventricular outflow tract is useful in treatment of a variety of congenital cardiac malformations. Seventeen patients underwent conduit reconstruction at the Texas Heart Institute between December 1965 and June 1974. Fifteen patients survived the operation and have significantly improved. Several different conduits were used: allograft aorta with the aortic valve and mitral leaflet attached, a woven Dacron prosthesis containing a prosthetic valve, a prosthesis containing a xenograft (porcine) valve and a valveless Dacron tube graft. Allograft conduits present difficulties with procurement and inventory and tend to calcify with time. Woven Dacron prostheses are favored because of ready availability in a wide range of sizes. In the case of pulmonary hypertension, we use a conduit containing a xenograft (porcine) value. The largest conduit possible must be used. Indications for conduit reconstruction include anomalous coronary arteries, discontinuity between the pulmonary arteries and pulmonary atresia with a VSD. Our current method of management of pulmonary atresia with VSD includes palliative shunt during infancy to permit full development of the pulmonary arteries for total correction at a more optimal age when a larger conduit may be used.


Topical lidocaine in preendoscopic medication. A double blind study of 111 consecutive elective upper gastrointestinal endoscopies performed with a flexible fiberoptic esophagogastroduodenoscope was made to determine the efficacy of topical pharyngeal anesthesia with lidocaine as an adjunct to intramuscular meperidine, intramuscular atropine, and intravenous diazepam. Patients who received lidocaine rated the over-all endoscopy and passage of the endoscope significantly easier than did those receiving placebo. The endoscopist found that patients who received lidocaine tolerated endoscopy significantly better, although gagging was not affected.


Modification and inheritance of pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae. A meiotic segregant (oliPR1) was isolated with a phenotype of multiple cross resistance and collateral sensitivity. Strain oliPR1 has increased sensitivity to ethidium bromide, dequalinium chloride, acriflavin, paromomycin and neomycin, and increased resistance to oligomycin, rutamycin, venturicidin, triethyltin bromide, antimycin, carbonylcynamide-m-chlorophenylhydrazone, tetra-N-butylammonium bromide, dibenzyldimethylammonium chloride, triphenylmethlphosphonium bromide, chloramphenicol, carbomycin, tetracycline, triton X-165 and cycloheximide. Single gene inheritance of the cross resistance and collateral sensitivity was shown by 2:2 parental ditype segregation and reversion of the complete phenotype by a spontaneous revertant. The locus conferring the oliPR1 phenotype was mapped 11.7 units from an unspecified centromere. Antibiotic resistance showed incomplete dominance, with the level of hybrid resistance dependent upon the inhibitor tested. Resistant diploids that produced four resistant ascospores were the result of mitotic recombination prior to meiosis. A partial revertant phenotype (sensitive to all inhibitors except oligomycin, antimycin and carbonylcyanide-m-chlorophenylhydrazone) was shown to be due to a single nuclear gene causing partial suppression of oliPR1. Anaerobic pretreatment, 37degrees and 0.5 MKC1 were observed to reduce the growth of oliPR1 when challenged with seven diverse inhibitors (antimycin, carbonylcyanide-m-chlorophenylhydrazone,-chloramphenicol, cycloheximide, oligomycin, triethyltin bromide, and triphenylmethylphosphonium bromide). Resistance to cycloheximide was not altered by the [rho--] state. A revertant of oliPR1 (sensitive to the above inhibitors but resistant to ethidium bromide, paromycin and neomycin) showed anaerobic and temperature sensitization to ethidium bromide, paromomycin and neomycin. Continuous monitoring of oxygen uptake by the revertant afteranaerobic pretreatment revealed that anaerbiosis sensitized respiratory adaptation of the revertant to neomycin. It is proposed that oliPR1 is a mutation resulting in the alteration of plasma membrane permeability to many diverse inhibitors.


Specialized transduction by bacteriophage P22 in Salmonella typhimurium: genetic and physical structure of the transducing genomes and the prophage attachment site. P22pro-1 and P22pro-3 are specialized transducing derivatives of phage P22 that carry the proA and proB genes of Salmonella typhimurium. These genes lie immediately adjacent to the prophage attachment site on the bacterial chromosome. By examining DNA heteroduplexes in the electron microscope, we found that DNA molecules from P22pro-1 and P22pro-3 each contain a substitution which adds length to the composite genome making the intracellular replicated genome too long to fit into a single phage particle. In this respect, and in many of their biological properties, the proline-transducing phages resemble P22Tc-10, another specialized transducing phage with an oversize, intracellular replicated genome which carries a tetracycline-resistance determinant from an R-factor.--Unlike P22Tc-10, however, P22pro-1 and P22pro-3 fail to integrate normally during lysogenizing infections, even when provided with all known integration functions. These results suggest that the proline substitutions have created a defect in the phage attachment site and suggest that the Campbell model for the formation of specialized transducing phages is applicable to phage P22 with the additional feature that oversize genomes can be produced and propagated.--A physical and genetic map of the P22 genome near the prophage attachment site was constructed which shows that the insertion from the R-factor in P22Tc-10 is not at the attachment site: it is therefore unlikely that P22Tc-10 was formed in an abnormal prophage excision event as envisioned in the Campbell model, but was instead the result of a direct translocation from the R-plasmid to P22.


Specialized transducing phages derived from phage P22 that carry the pro AB region of the host, Salmonella typhimurium: genetic evidence for their structure and mode of transduction. Two independently isolated specialized transducing phages, P22pro-1 and P22pro-3, have been studied. Lysates of P22pro-1 contain a majority of transducing phages which can go through the lytic cycle only in mixed infection; these defective phages transduce by lysogenization in mixed infection and by substitution in single infection. A few of the transducing phages in P22pro-1 lysates appear to be non-defective, being able to form plaques and to transduce by lysogenization in single infection. Transduction by P22pro-3 lysates is effected by non-defective transducing phages, which transduce by lysogenization; these lysates also contain a majority of defective phages which do not co-operate in mixed infection. The P22pro-1 genome is thought to contain an insertion of bacterial DNA longer than the terminal repetition present in P22 wild type, so that at maturation a population of differently defective phages is produced. The exact structure of the P22pro-3 genome is open to conjecture, but it seems clear that the insertion of bacterial DNA is smaller than that in P22pro-1. Both P22pro-1 and P22pro-3 are defective in integration at ataA under non-selective conditions, although both integrate on medium that lacks proline.


[Recombination of mitochondrial markers in yeasts. I. Analysis of isomitochondrial crosses and a study of the influence of locus determining mating type on recombination]. Yeast mitochondrial markers of the resistance to antibiotics (erythromycin, neomycin and monomycin) were used to study mitochondrial recombination in bifactorial crosses both in cis and trans configurations of markers. Our strains of Saccharomyces cerevisiae are isochromosomal and isomitochondrial due to all of them have originated from one haploid pace XII of Sacch. cerevisiae. The following parameters of mitochondrial recombination were examined in random samples of zygotic diploid daughter colonies; a) the asymmetric transmission of parental classes; b) the frequency of recombination; c) the polarity of recombination; d) the effect of cell mating type on these parameters in reciprocal crosses. The data obtained suggest the following features of mitochondrial recombination: a) The distribution of both classes as parental and recombinant is unequal: there is asymmetrical transmission (0,22-1,72) and some polarity of recombination (up to 4,0). b) The effect of cell mating type on asymmetrical transmission was established only is some crosses in trans-configuration of mitochondrial markers. In cis-configuration crosses such effect was not observed. c) Different mitochondrial mutations influenced on all the above listed parameters (asymmetrical transmission of parental classes, the frequency and the polarity of recombination). Some correlation between the high level of asymmetrical transmission of parental classes and the low frequency of recombination was found in crosses with NR and MR mutants. The existence of several different loci among ER, NR and MR mutants is suggested on the basis of the data on the recombination frequency.


[Co60 gamma-ray sensitivity of a series of strains of Saccharomyces cerevisiae yeasts bearing different mutations. I. Radiosensitivity of haploid strains]. Sensitivity to gamma-rays Co60 of haploid strains of Saccharomyces cerevisiae carrying ade1-6 mutations and dominant, semidoninant and recessive suppressors was investigated. It was shown that 3 out of 4 studied strains with ade1-6 mutation had reliable increased radioresistance. The increased radioresistance was observed also in strains carrying, beside ade1-6 mutation, dominant and semidominant suppressors. However the strain carrying a recessive suppressive mutation turned to be radiosensitive. A conclusion is drawn that rediosensitivity of yeast cells can be influenced by different mutations affecting the process of cell metabolism.


[Effect of adenine, adenosine and adenylic nucleotides on the mutagenic action of hydroxylamine]. The effect of some adenyl precursors of DNA synthesis on the mutagenic activity of hydroxylamine (HA) is studied. It is shown that the addition of adenine to a suspension of Escherichia coli B cells increases the yield of mutants by more than two times as compared with HA alone. The effects of adenosine, AMP and dAMP are somewhat different. It is suggested that the increase of the HA mutagenic effect produced by the addition of adenine may be due to: 1) the excess of the amount of adenylic precursors of DNA synthesis over guanilic ones, which promotes the erroneous base-pairing during the replication of the HA modified template; 2) the modification of adenylic precursors by HA into N6-oxy-dATP, and their incorporation into DNA. The mutagenic effect of N6-hydroxyadenosine, the product of the adenine modification by HA, in E. coli B pur- was studied. The experiments showed that N6-hyrdoxyadenosine induced about 1% of mutations, a relatively low lethal effect (the cell survival was 80%), and provided a high mutagenic action of this compound.


[Detection of the products of several T4B phage genes among the proteins of infected Escherichia]. Proteins of wild-type phate T4 and its mutants in genes rII, su(30), stII, stIII, rVI-39 and 60 are studied by means of polyacrylamide gel electrophoresis in the presence of sodium dodecylsulphate of membrane fractions and lysates of infected bacteria. Physiological studies of mutants in these genes carried out by the authors and other investigators allow to suggest that when functions are realized, the products of these genes interact with the plasmatic membrane of the infected bacteria. The product of rIIB cystrone has been indentified as the protein of the membrane of an infected bacterium, its molecular weight being about 30 000. The products of genes su(30), stII, stIII and rVI could not be identified either in lysate or in membrane fraction. The function of gene stII is "superstoichiometric", which may be due to the involvement of a very small product amount when the function of gene stII is realized. Mutants in genes 39 and 60 lack one and the same protein with molecular weight of about 40 000 which is a protein of the membrane of an infected bacterium. This protein may be a product of gene 39, and the functional product of gene 60 is necessary to synthesize it.


[Genetic control of the RecF recombination pathway. II. Effect of recL- and uvrE- mutations]. It was found earlier that the effect of the uvrE- mutation on the yield of recombinants formed via RecF pathway of recombination was mainly due to the decreased viability of the recB-C-sbcB-uvrE- recipient. The results of the present paper show the uvrE- and recL- mutations reduce the recipient ability of the recB-C- sbcB- strains to the same extent. We were unable to find any evidence for complementation between the recL- and uvrE- mutations in transient as well as in stable uvrE-/recL- merozygotes. The recL152 as well as the uvrE502 mutation is lethal for the strains deficient in DNA polymerase I. Both recL- and uvrE- mutations reduce in the recB-C- sbcB- strains the probability of inheritance of the proximal non-selective donor markers as well as selective markers located close to the leading end of the donor chromosome. The former effect however could not be completely due to the latter.


[Isolation and study of bacteriophage T4B mutants according to genes functioning at an early stage of the infectious process]. In previous study irreversible inactivation of rII(ts)-infected lambda-lysogenic bacteria at 42 degrees C was revealed. The inactivationprocess depended on active protein synthesis...


Kidney transplants in patients over 50.

Kidney transplants in patients over 50. Patients with end-stage renal failure shouldn't be denied the only possibility of cure just because they're old or have other chronic diseases. In this study of 69 patients over age 50-the largest series reported from a single medical center-kidney transplants from related donors had the same high rate of success as in younger patients. Over 80 percent of the patients who received kidneys from their children or siblings are still alive, in contrast to 52 percent of those who had to settle for a cadaver kidney. Infection posed the most serious hazard after surgery. Late complications, particularly hypertension and diabetes, were easily controoled and by no means debilitating. Four of the survivors still need hemodialysis, but over two-thirds have recovered completely.


A controlled study of the EEG during transcendental meditation: comparison with hypnosis. A controlled, quantitative investigation of the electroencephalogram (EEG) and transcendental meditation (TM) revealed that EEG changes during TM were rarely as pronounced or consistent as previous reports suggest. There was considerable variation between subjects, some displaying no EEG changes at all during TM compared with an equal period of non-meditation. Any changes that did occur in a particular individual were not necessarily repeated in a subsequent session. A comparison of mean EEG parameters of the experimental group revealed no consistent significant differences between meditation and non-meditation, although trends towards increased theta and decreased beta activity during meditation were apparent. The biggest differences in mean EEG parameters were between subject groups. In particular, the group of meditators exhibited significantly more theta activity (during both TM and non-meditation) than a randomly selected group of individuals that had never meditated or been hypnotized. The EEG characteristics of the group of meditators were similar to those of a group of subjects experienced in self-hypnosis. It is concluded that the most obvious EEG changes during meditation are long-term. In people who regularly practise TM (or self-hypnosis), the EEG gradually (over weeks or months) tends to "slow down." Such a "slowed down" EEG is apparent during both normal waking conditions and altered states of consciousness in these individuals.


[Therapy of duodenal ulcer. Comparative study on the hospital treatment of duodenal ulcer under endoscopic control of progress with and without drug support]. In a controlled study of 4 weeks--performed on 3 groups of 15 hospitalized patients each with endoscopically demonstrated florid duodenal ulcers--the healing process was checked by endoscope after 14 days and 4 weeks. The first group was treated with the preparation Caved-S, the second received an antacid mixture, and the third group was at first given no specific therapy but a placebo and later on an additional small quantity of antacids. The quickest relief of the pain symptoms was seen in the group treated with Caved-S. Healing was assessed endoscopically after the scheme of Ohmori and Miva and yielded after 14 days a varying number of healing stages for all 3 groups; after 4 weeks there was positive healing-up in a varying number of patients. All 45 patients were clearly improved after 4 weeks. The healing rate in those who had received Caved-S was slightly better than in those who had been treated with antacids and significantly better than in those patients who had been given small quantities of antacids only later on. It becomes apparent again that hospitalization alone leads to ulcer healing in over 60% of cases, which excludes the evidence of an influence of drugs.


Attempts at perfect normalization of glucose tolerance test of severe diabetics by artificial beta cell. The artificial beta cell is a Glucose Controlled Insulin (and dextrose) Infusion System (GCIIS) for maintaining normoglycemia in diabetic conditions and other disturbances of metabolism. The insulin and dextrose infusion rates are calculated by a microcomputer according to the static glucose concentration (proportional control) and to its rate of change (dynamic control). The algorithms controlling the computer can be adapted to the subjects' requirements. It has already been shown, that the artificial beta cell is able to maintain blood sugar values in diabetics within physiological ranges during the course of the day. In our present study we examined the response of the artificial beta cell using a 100 gm oral glucose load in severe diabetics. The first type of control algorithms applied effected a rather small initial insulin infusion following OGTT in 8 juvenile diabetics connected with the artificial beta cell. The glucose responses thus obtained were similar to latent diabetes. In contrast, when the computer was controlled by the second type of algorithms with a more responsive dynamic control and a consequently higher initial insulin infusion, in one diabetic OGTT was fully normalized, whereas an improvement was achieved in another diabetic patient. Furthermore it was shown that control algorithms must be varied individually, depending on residual beta cell function and glucose regulatory mechanisms.


Effect of fasting on the incorporation of [3H]-L-phenylalanine into proinsulin-insulin and total protein in isolated rat pancreatic islets. Pancreatic islets of fed, 24 hr and 72 hr fasted rats were incubated with [3H]-L-phenylalanine at verious concentrations of glucose. Total islet protein was isolated by TCA-precipitation, proinsulin-insulin by polyacrylamide gel electrophoresis. The incorporation of label was expressed per mug dry islet weight. Fasting for 24 hr reduced the incorporation of label into (pro)insulin at glucose 3 mg/ml, but not at glucose 1 mg/ml. After 72 hr of fasting the incorporation into (pro)insulin was decreased both at glucose 1 and 3 mg/ml and the slope of the dose-response curve for glucose stimulation was reduced by 31%. In contrast, fasting caused the incorporation into total islet protein to increase. A similar tendency was observed in an unidentified protein fraction, which failed to migrate from the spacer gel on disc electrophoresis. Fasting did not affect the islet DNA content per mug dry weight. These results suggest that fasting reduces the rate of insulin biosynthesis by decreasing the glucose sensitivity of this process. Fasting may stimulate, however, the biosynthesis of an unidentified islet protein component.


Phenylalanyl-tRNA synthetase from baker's yeast: specificity and quantitation of affinity elution with tRNA. TRNAPhe is able to elute phenylalanyl-tRNA synthetase from cation exchangers in a 1:1 ratio. Elution of phenylalanyl-tRNA synthetase in a 1:1 ratio is also observed for four noncognate tRNAs investigated, specific for valine, serine, isoleucine and tyrosine. If protein mixtures are subjected to affinity elution the cognate pair [tRNAPhe-phenylalanyl-tRNA synthetase] is eluted first, followed by noncognate pairs. The unspecific elution is not influenced by complexation of phenylalanyl-tRNA synthetase with an analog of phenylalanyl-adenylate.


The sequence determination of a protein in a micro scale: the sequence analysis of ribosomal protein L34 of Escherichia coli. The complete amino acid sequence of ribosomal protein L34 has been established by improved micro techniques with 3 mg of the lyophilized protein. The protein was digested with trypsin, thermolysin and chymotrypsin and the resulting peptides were isolated from fingerprints performed on cellulose thin-layer plates. The amino acid sequences of the peptides were determined by the combined micro dansyl-Edman technique using 5 - 10 nmol per sample. Aspartic acid and glutamic acid were distinguished from their amides by use of the color reaction of ninhydrin with the respective amino acid phenylthiohydantoins.


Naturally occurring immunosuppressive agents. II. The ability of cell-free liver extracts to modify the rejection of allogeneic skin grafts in the rabbit. It has been demonstrated that cell-free extracts of pig, rabbit and human liver, but not of other parenchymal organs, contain a factor or factors capable of suppressing the proliferative responses of allogeneic and xenogeneic lymphoid cells stimulated with PHA, PWM, Con-A and allogeneic lymphocytes. Intravenous injection of the liver extract is capable of modifying significantly the skin allograft rejection reaction in normal adult outbred rabbits. Work is now in progress to isolate this factor and to determine its composition.


Effect of endocrine manipulation on graft rejection. Immune competence (as determined by xenograft rejection) was measured following classical endocrine ablation and replacement procedures in the adult rat. Graft rejection, expressed as initial rejection time, was not changed by thyroidectomy, adrenalectomy, or hypophysectomy, either with or without appropriate hormone replacement. In concrast, gonadectomy in 3 rat types (female Sprague-Dawley, male and female Long Evans) decreased initial rejection time; administration of physiological doses of 17beta-estradiol plus progesterone returned the initial rejection time of ovariectomized rats to that observed in unoperated controls. Since initial rejection time was neither decreased by secondary ovariectomy (hypophysectomy) nor increased by sex steroid administration to hypophysectomized rats, it was suggested that the increased immune response after ovariectomy may be due to the presence of an immunopotentiating pituitary factor(s). Although commerical preparations of follicle-stimulating hormone, luteinizing hormone, and luteotropic hormone were found to mimic the effect of ovariectomy, the impurity of these preparations (as judged by isoelectric focusing gels) precluded any conclusion as to the nature of the postulated immunopotentiating factor.


The mitotic activity of, and antibody production by, sensitized lymphocytes quantified after transfer into irradiated recipients. Adult thymectomized, irradiated CBA mice were reconstituted with bone marrow and thymus grafts derived from congenic strains differing in immunoglobulin allotype. After challenge with heterologous erythrocytes the allotype of the antibody secreted by the chimaeric spleen cells was the same as that of the bone marrow donor. When mixtures of immune and non-immune cells from the two congenic strains were transferred to irradiated recipients, a preponderance of the immune-donor cells was found dividing in the recipients' spleen 3 days after challenge with the immunizing antigen, and the allotype of the antibody-producing cells 7 days after challenge was almost entirely of immune-donor derivation. Further quantitative studies on the number of mitotically reactive cells observed after immunization with heterologous erythrocytes indicate that after primary and secondary challenge the mitotic activity of these cells is increased respectively four and eight times relative to that found in unsensitized cells.


Biological effects of Escherichia coli lipopolysaccharide (LPS) in vivo. II. Selection in the mouse thymus of PHA- and con A-responsive cells. The effect of LPS injection on mouse thymocytes was examined by in vitro stimulation with PHA and Con A. Thymocytes from LPS treated mice were found more responsive than normal thymocytes to PHA and Con A. The increase of responsiveness was different for PHA and Con A, and dependent on the dose of LPS injected. This dose dependency suggests that LPS in vivo modifies the thymocyte population by progressively eliminating T1 cells and selecting T2 cells. These effects seem to be mediated by corticosteroids because they were prevented by adrenalectomy, a finding in agreement with the notion that the injection of cortisone induces similar cell changes in the thymus.


Local immunie response in experimental pyelonephritis in the rabbit. III. Lymphocyte responsivieness to O and K antigens of Escherichia coli. The response of circulating and infected kidney lymphocytes to the O (lipopolysaccharide) and K (polysaccharide) antigens of an Escherichia coli O6 K 13 H1 strain was determined. Both circulating and kidney lymphocytes showed significant incorporation of [3H-methyl]thymidine into DNA when incubated with the O antigen, whereas neither responded to the K antigen. The lipid moiety of the lipopolysaccharide was required for lymphocyte responsiveness. Upon sequential incubation of O antigen and fluoresceinated homologous antiserum, 24-30 per cent of kidney lymphocytes were shown to have surface receptors for O antigen, whereas none had surface receptors for K antigen. Although the K antigen is an important determinant of invasiveness of the upper urinary tract, it fails to elicit a cellular immune response or attach to lymphocytes from the infected kidney in experimental pyelonephritis.


Chemical properties of antigen-dependent migration inhibition factor in mice. Antigen-dependent migration inhibition factor produced in cultures of mouse lymph node lymphocytes was further characterized. It was found to bind to Concanavalin A and could be eluted by the appropriate sugar. The pI of the activity was found to be between 6-4 and 6-5 by isoelectric focusing.


Response of guinea pigs and hamsters to experimental infection with Mycoplasma pneumoniae. In an effort to further delineate the mechanism of infection and pathogenicity of Mycoplasma pneumoniae infections, the hamster and guinea pigs were used as experimental models. These animals were chosen because of previous experience. The local antibody response in addition to organism growth patterns were examined in detail. Histological examination was carried out to determine the pathological lesions which occur. The significance of these findings is discussed.


The incidence of Mycoplasma pneumoniae infections in Denmark over the past seventeen years: a review. The variations in the incidence of Mycoplasma pneumoniae infections in Denmark over a period of 17 years could be demonstrated in the central serological laboratory which serves the whole of the population. This observation was made possible for the first and major part of this study by testing cold agglutinin (CA) positive sera, which had been kept frozen sine 1958, for antibodies to M.pneumoniae. The second part of the study is based upon results from routine tests for CA and M.pneumoniae antibodies on all samples which we receive. A statistical analysis of the total material indicates that four epidemics of M.pneumoniae antibodies on all samples which we receive. A statistical analysis of the total material indicates that four epidemics of M.pneumoniae infection had taken place from January 1958 to December 1974 and that these epidemics occurred at regular four and a half year intervals. By a follow-up of the study a fifth epidemic was demonstrated during the first eight months of 1975 which broke the regular periodicity by appearing two years earlier than expected. The consequences of including only CA positive sera in this study was investigated. Antibodies to M.pneumoniae were measured by either an indirect immunofluorescence test, an indirect haemagglutination test or a complement fixation test. The observed difference in sensitivity of these tests is discussed in relationship to a possible influence on the overall incidence.


The use of organ cultures and animal models in the study of Mycoplasma pneumoniae infections. Organ cultures of ciliated tracheal epithelium derived from various animal species have been used to study several different mycoplasma infections. Human and hamster tracheal cultures have been used in particular to study Mycoplasma pneumoniae which, of all the human mycoplasmas, is the only one which damages the cultures. One reason for this is the capacity of the virulent organisms to attach to the cells; strains which are prevented from attaching or have lost this capacity do not damage the cultures. The organ culture system is therefore valuable in looking at the organisms-cell relationship but it is necessary to use animal models to study immunological processes. Hamsters, and more recently guinea pigs, have been used in this respect. The hamster model has been used to study the pathogenesis of M. pneumoniae pneumonia and also recovery from and resistance to infection. Humoral immune mechanisms seem more important than cell-mediated mechanisms in resistance, and the probable importance of local immunity is discussed. It is pointed out that it should be possible to establish the mechanisms underlying the development of M. pneumoniae sequelae where conditions, similar to those seen in man, occur in animals. Finally, the way in which the hamster model has been used to study the effect of tetracycline and erythromycin on the course of disease is discussed. As in man, therapy often improves the pneumonia but does not eradicate the organisms. This is probably due, at least in part, to the fact that the antibiotics are only mycoplasmastatic. Drugs with mycoplasmacidal properties are needed and the animal model would obviously prove helpful in evaluating these.


The incidence and aetiology of respiratory tract infections in general practice--with emphasis on Mycoplasma pneumoniae. The incidence of respiratory tract infections in patients seeking medical advice at a community care centre (Dalby) during 1973 and 1974 was studied. About every third patient seen at this primary health station presented with signs of such infections. In the age groups less than 10, 10-19, 20-39, 40-59 and greater than or equal to 60 years, respiratory tract infections accounted for 65, 45, 32, 18 and 9% of the fotal number of diagnoses made during 1974. The aetiology of acute respiratory tract infections in a series of patients seen at this health station was studied. The series included randomly selected cases, but excluded children under seven years of age and patients presenting with signs of acute otitis media and tonsillitis. Attempts to establish the aetiology were made on the basis of the history, the clinical examination, and cultures for beta-haemolytic streptococci and Mycoplasma pneumoniae, complement foxation tests for influenza A and B, para-influenza 1, 2, and 3, adeno, cytomegalovirus and respiratory syncytial virus, and Chlamydia psittaci. Paul-Bunnell test and tests for cold agglutinins were also performed. With this test battery, an aetiological diagnosis was obtained in only 33% of the 101 patients studied. The findings suggest an infection with M.pneumoniae in 16%, with beta-haemolytic streptococci in 9%, and with viruses (adeno and para-influenza) in 7% of the patients. The present communication highlights the role of M.pneumoniae in upper respiratory infections, as few data have appeared on such infections in patients seen in general practice. The difficulty of establishing the aetiology of respiratory tract infections and the consequent treatment dilemma is discussed.


Pathogenicity factors of mycoplasmas.

Pathogenicity factors of mycoplasmas. The pathogenicity of mycoplasmas is caused by several factors, e.g. exotoxin, toxic properties of membrane components, exoenzymes, peroxide, and immunological factors. The absence of a rigid cell wall and the small genome tend to influence the interactions between mycoplasmas and host tissue. Mycoplasmas do not have a cell wass and are therefore resistant to the action of the host's lysozymes. They appear in some patients to be immunologically inconspicuous and in other patients they have been reported to have an immuno-suppressive effect. Recently there have been reports of central nervous system disorders due to mycoplasma. The pathogenic factors involved in these reactions have not been elucidated. Other aspects of Mycoplasma pneumoniae pathogenicity are also discussed.


An examination of the immunology of cancer patients. We have examined 111 cancer patients and 111 control individuals for general immunocompetence (haematological values, "recall" antigen skin tests, PHA and PPD induced lymphocyte transformation, serum Ig levels and lymphocyte subpopulations), for evidence of sensitisation to tumour-associated antigens (leucocyte migration test, serum inhibition of autologous leucocyte migration, lymphocytotoxicity, membrane immunofluorescence and immune adherence) and for evidence of continuing immune reactions (alterations of complement components and anticomplementary activity). Major differences between the cancer patients and controls were demonstrated by several tests of sensitisation and these also detected differences between patients with and without metastases. The only differences detected between cancer patients and controls by the tests of general immunocompetence were in serum IgG and IgA (higher in the cancer patients) and lymphocyte subpopulations ("active" T, autorosetting lymphocytes and lymphocytes forming "super-rosettes" increased in cancer patients). In a comparison of cancer patients with and without metastases, patients with metastases were less often reactive to the Candida DHS and streptokinase-streptodornase antigens and had raised circulating Fc positive cells. Abnormalities of the individual components of complement occurred in about half the cancer patients, but were equally common in those with and without metastases. Serum anti-complementary activity was very rarely detected. The tests of specific sensitisation correlated reasonably well but correlations of tests of general immunocompetence were infrequent.


Circulating immune complexes in sera of patients with Burkett's lymphoma and nasopharyngeal carcinoma. Sera of individuals with Burkitt's lymphoma and nasopharyngeal carcinoma, tested by consumption of hemolytic complement, were found by comparison with healthy individuals to have significantly increased levels of circulating immune complexes. The identity of the immune complexes was established by sucrose density gradient ultracentrifugation, which showed them to sediment between 10 and 19S. As they were adsorbable by rheumatoid factor--Sepharose 4B conjugates, it appeared that these complexes were composed of IgG. The complexes were retained by Concanavalin A--Sepharose columns and eluted by alpha methyl-D-mannoside, suggesting by analogy with model complexes that the antigens might be glycoproteins.


Inhibition of syngeneic tumor growth in rats immunized with allogeneic skin grafts. The growth of a transplantable tumor (KMT-17) in syngeneic Wistar King Aptekman/Mk (WKA) rats was inhibited by preimmunization with allogeneic normal cells from Donryu strain rats. The phenomenon is referred to as allogeneic cell immunity. A slight inhibition was observed in rats immunized with normal liver, spleen, kidney, embryonal cells, whole blood and white blood cells from allogeneic Donryu rats. A strong inhibition was observed in animals which had rejected allogeneic skin grafts, particularly from the Donryu and Kyoto rats. The inhibition was comparatively weak after immunization with skin grafts from the Long Evans, ACI, Buffalo, Ficsher, Sprague Dawley or Tokyo allogeneic rat strains. This immunizing effect was dependent on the viability of the grafts and was easily abrogated by low-dose irradiation. The mechanism of allogeneic cell immunity is considered to be a non-specific stimulation of the immunity against antigenic tumors in the syngeneic host


The misalliance dimension in Freud's case histories: i. The case of Dora. This paper presents an effort to identify sectors of therapeutic misalliance between Freud and his patient Dora based on modifications in the framework of the analytic relationship and situation. Use is made of a template based on the current ground rules and boundaries of the patient-analyst relationship, and three deviations from this template are identified in Freud's analytic work with Dora. The intrapsychia and interactional sequelae of these deviations in technique for Dora and for the course of her analysis are traced out. The consequent sectors of misalliance are identified and the participation of both Dora and Freud is described, as are their respective, largely unconscious efforts to modify these areas of unconscious collusion. Stress is placed on Dora'a unconscious preceptions of the actual implications of Freud's modifications in the frame. The role of Freud's failure to rectify these deviations and to analyze their implications for Dora are considered, including their influence on the patient's premature termination of her analysis.


Psychoanalytic contributions to the relationship between dreams and psychosis--a critical survey. The author surveys psychoanalytic contributions to the relationship between dreams and psychosis as well as adding some of his own observations. He uses as his frame of reference questions relating to the similarities between dreams and psychosis, whether there are psychotic dreams and whether dreams may presage psychosis. There seemed to be some general consensus that the answers to these questions were positive, depending upon the frames of reference used, i.e., whether one referred to the topographical or structural model of the mind, the level of ego cathexis, the function of the ego vis-a-vis reality, etc. Most contributors felt that a dream taken out of context from the overall clinical situation would be difficult to evaluate as either presaging or representing a psychosis despite the fact that many dreams may appear which are suggestive.


[Sugar substitutes in the diabetic diet]. The decreased glucsoe utilization in diabetes mellitus justifies the use of sugar substitutes ("diabetic sugar") if two conditions are fulfilled: 1)The sugar substitute should be a carbohydrate which does not lead, or only to a slight degree, to hyperglycaemia and thus, in this respect, differs distinctly from sugars such as glucose and saccharose. 2) The sugar substitute must not cause undesired side-effects. The absorption, utilization and side-effects of the sugar substitutes fructose, sorbitol and xylitol were investigated. They were found to be more slowly absorbed than glucose and thus to offer the advantage of better utilization under conditions of limited insulin production. However, the particularly slow passive absorption of sorbitol and xylitol can sometimes be a disadvantage, since osmotic diarrhoea may occur after administration of high oral doses. The sugar substitutes enter the metabolism enzymatically and are utilized mainly in the liver. The peripheral state was investigated after intravenous, intraduodenal and oral administration of glucose and fructose to healthy subjects. Liver metabolism was examined (Dietze) by comparing hepatic venous and arterial concentrations after intravenous administration of the sugars. Also, diabetic patients received glucose and fructose orally. As previously demonstrated, the investigations using several techniques showed a smaller influence on blood glucose and serum insulin concentrations after administration of fructose, sorbitol and xylitol than after glucose. If no metabolic changes occur after intravenous administration of high doses, no such changes need be expected after oral administration of small doses. Nor did measurements in hepatic venous blood (Dietze) show any marked effect of fructose on the blood glucose level. The healthy subjects showed no significant changes in blood glucose or serum insulin concentration after either intraduodenal or oral administration of fructose, whereas they showed a considerable increase after glucose administration. Investigations in adult-type diabetics revealed a better utilization of fructose than glucose. With correct dosage, sugar substitutes are able to increase the carbohydrate tolerance and, under certain conditions, to achieve a relative stabilization of the metabolism of unstable diabetics. The antiketogenic activity of sugar substitutes is particularly pronounced. Side-effects such as high blood levels of urea, lactate, triglycerides and bilirubin or a decrease in hepatic adenin nucleotides do not occur after oral administration, nor are they of importance after intravenous administration with correct dosage. The osmotic diarrhoea occurring after intake of sorbitol or xylitol is caused by their slow absorption and limits the consumption of these sugar substitutes. In the often obese adult-type diabetics, the calorie intake inherent in the consumption of diabetic sugars may have an unfavourable influence on their weight...


Possible mechanisms for the cariostatic effect of xylitol. Xylitol appears to be the only known cariostatic natural carbohydrate which meets most of the desiderata for a sweetener in the human diet. Possible mechanisms for this cariostatic action can be derived from a consideration of the factors which may be operating at a molecular and microbiological level. These include: a) Molecular size and e.g. the short, open-chain structure and absence of reducing groups b) Absence or relative lack in most oral microorganisms of xylitol-binding factors in dental plaque c) Lack of bacterial genes coding for xylitol-utilizing enzymes or of inducible or de-repressible genes for this purpose d) Inhibition of enzymes involved in cariogenesis (competitive in case of some isomerases) e) Enzyme specificity requirements f) Higher osmotic pressure exerted by xylitol as compared to hexoses and disaccharides g) Ability of xylitol to produce a favourable electrolyte concentration in the saliva without lowering plaque pH h) Ability of xylitol to increase the secretion and activity of salivary lactoperoxidase and certain other (muco) proteins. Xylitol may enhance the adsorption of glycoproteins on the tooth surfaces and strengthen the acquired pellicle.


Long-term tolerance of healthy human subjects to high amounts of xylitol and fructose: general and biochemical findings. Three groups of volunteers, totalling 125, lived for two years on strict diets so that comparisons might be made with regard to the sweeteners: fructose (F), sucrose (S), and xylitol (X). The sizes of the test groups were: S, 35; F, 38; X, 52. The average monthly amounts of the sugars consumed in a varied assortment of foods were: S, 2.2 kg; F, 2.1 kg; X, 1.5 kg. The highest daily doses of fructose and xylitol were 200 - 400 g (maximum 430 g xylitol). Serum samples were analyzed for several chemical parameters. The dietary regimens did not result in clinically significant changes between the sugar groups. The ability of X to produce osmotic diarrhoea and flatulence was found to depend on the individual physiological responses of each volunteer. In many cases no symptoms were found although high amounts (200 - 400 g) of X were consumed. All pregnancies and deliveries in the F and X groups were normal. Practically all the volunteers accepted the F and X foods (almost 100 varities) and adhered to the dietary regimen for two years. This was due in the main to the fact that most F and X products were comparable to those containing sucrose.


Dextran uptake into, and loss from, corneas stored in intermediate-term preservative. This investigation demonstrates that dextran passes into rabbit corneas stored in M-K medium prior to corneal transplantation. An equilibrium between dextran in the cornea and in the M-K medium is reached at about 24 hours. Post-keratoplasty dextran efflux is rapid with about 70 to 75 per cent being lost within one to three hours and 99 per cent being lost in 12 hours.