Reactogenicity to primary and repeated vaccination with influenza split virus vaccine. Influenza vaccines (split, adsorbed, low nitrogen) of two different antigen concentrations (commercial production) were administered to 1,111 adult persons of both sexes. Up to five previous vaccinations had been given to the population under observation. Their reactions both local and general were not different in primo-vaccinees or boostered persons. Increasing numbers of previous vaccinations were not reflected by increasing rates of complaints. Disregarding immunization history, the group given the higher concentrated vaccine showed a lower rate of side effects while the lower antigen concentration produced a higher rate. The relevance of the observation that no sensitizing effect occurred in persons with up to five vaccinations may be a characteristic of split adsorbed influenza vaccines of high purity.


Strain-specificity of antibody to haemagglutinin following inactivated A/port chalmers/1/73 vaccine in man: evidence for a paradoxical strain-specific antibody response. An analysis was carried out of the anti-haemagglutinin antibody responses in adult human recipients of inactivated whole virus A/Port Chalmers/1/73 (H3N2) vaccine using single radial diffusion combined with antibody adsorption techniques to determine antibody specificity. Antibody was characterised as cross-reactive (i.e. directed against antigenic determinants of haemagglutinin which are common for viruses within the H3 subtype) or strain-specific. Strain-specific antibodies for the vaccine strain and also for A/Hong Kong/68(H3N2) virus were assayed. A high proportion of vaccinees developed antibody of the cross-reactive specificity. The titre and frequency of such antibody increased with vaccine dose (100 iu to 1600 iu per dose). Many individuals developed strain-specific in addition to cross-reactive antibodies. A notable finding was that in 70% of vaccinees who developed strain-specific antibody, this was a paradoxical response directed against the strain specific determinant of A/Hong Kong/68 virus (the first number of the H3 subtype). Only 30% developed strain-specific antibody to the haemagglutinin of the vaccine strain. The percentage of vaccinees developing strain-specific antibodies to the vaccine strain was not significantly increased by increasing the dose of vaccine to 1600 iu. A second dose of A/Port Chalmers/73 vaccine administered approximately one year after the first dose only slightly increased the percentage with A/Port Chalmers strain-specific antibody.


Effects of vaccination on an influenza epidemic in a geriatric hospital. During winter 75/76 (from February 1 to March 31) we got the opportunity to follow the incidence of an influenza epidemic that occurred in the geriatric hospital of Ivry. Its population was, on the average, 83 years old. 958 persons were involved in this study: 523 out of them had been vaccinated with Pasteur bivalent Mutagrip A + B vaccine. The epidemic had a double origin: it was due to a virus A/Victoria and to a virus B/Hong Kong. A significant difference was noted between the vaccinated group and the nonvaccinated one. Serological (CF and HI) and virological investigations (virus isolation) were performed on 110 subjects. The clinical course followed by the disease was mild for the vaccinated and severe for the nonvaccinated. Mortality rate was 0.19% in the former against 3.90% in the latter. It has been thus possible to observe an "immunological fence" since it appears that when 79% of a given unit has been vaccinated, influenza incidence has been as much as three times reduced.


Use of influenza vaccine in non-high risk populations. The aim of most strategies for vaccination against influenza is the prevention of mortality. Since individuals in the high risk group are mainly elderly, and the elderly have a low frequency of influenza infection, this strategy can have no significant controlling effect on morbidity. It has been shown in the longitudinal community study in Tecumseh, Michigan that highest frequency of infection with influenza is seen in the school-age population; this pattern is quite marked for type B influenza and less so for type A. In addition, it was possible in 1968-69 to show that vaccination of schoolchildren with an inactivated H3N2 vaccine resulted in a three-fold reduction in the attack rate for the entire community. Because of a number of problems in use of inactive vaccines, including the need for parenteral administration, it is unlikely that such preparations could be used regularly on this large a scale. However, it would be entirely feasible for live virus vaccines to be employed in such a manner. The use of more extensive vaccination would have an additional beneficial effect, since it has recently been shown in Tecumseh that a relationship may well exist between frequent respiratory infections and the development of chronic bronchitis in apparently healthy individuals.


In vitro markers for measuring residual virulence for men of live attenuated influenza viruses. Human and equine influenza strains attenuated by consecutive passages in the presence of normal horse serum (NHS) on allantois-on-shell system (AOS) and administered to human volunteers or horses as possible live virus vaccine candidates were tested in organ cultures of ferret and hamster trachea. Temperature sensitivity, virus replication, interferon induction and neuraminidase activity were also investigated. Observation of the ciliary activity of each ring was made daily. Influenza strains which were incompletely attenuated following two to five passages on AOS + NHS system and caused severe to mild symptoms of influenza in volunteers or horses also caused a 50% inhibition of the activity of the ciliated epithelium earlier than did completely attenuated strains following ten passages on the same system. The A/Hong Kong/68 strain attenuated by Beare and Bynoe was used as a reference strain in every test. This technique appears to be valuable for screening live influenza vaccine candidates and may prevent risking severe illness in volunteers. No significant results could be ascertained with other markers investigated.


Segregation of an internal biochemical marker during influenza virus recombination and its possible correlation with biological properties. The internal matrix proteins of A/Okuda/57, A/Finland/4/74 and A/New Jersey/8/76 viruses and several recombinant strains have been examined by radioiodination of the purified proteins followed by peptide mapping. The method is rapid and requires only small amounts of material. Reproducible differences were detected between the matrix proteins of the above parents and allowed the origin of the matrix proteins of the recombinant viruses to be determined. The use of matrix protein identity as a marker in recombination work and its possible correlation with biological properties of the virus is discussed.


IgM and IgG antibody responses following immunization of children and adults with influenza A/NJ/76 vaccines. The character of the immune response to inactivated monovalent influenza A/New Jersey/76 (A/NJ/76) and bivalent influenza A/New Jersey/76-A/Victoria/75 (A/NJ/76-A/Vic/75) vaccines was studied in children 6 months to 18 years of age. Hemagglutination-inhibiting antibody levels were measured in post-vaccination serums before and after 2-mercaptoethanol treatment. IgG antibody predominated in responses to the influenza A/Vic/75 component of bivalent vaccines. In contrast, specific IgM antibody against influenza A/NJ/76 developed after both monovalent and bivalent vaccines, and appears to characterize the immune response to this antigenic "shift" strain in children. Prevalences of IgM antibody against influenza A/NJ/76 did not differ significantly by age, implying that type rather than extent of previous influenza experience determines the IgM antibody response to an antigenic "shift". Slit-product vaccines produced significantly fewer IgM antibody responses to influenza A/NJ/76 than did whole-virus vaccines, a phenomenon which may correlate with their diminished reactogenicity and immunogenicity in children.


Field observations on influenza vaccination among horses in Britain, 1971-1976. The observations reported in this paper were obtained as part of a long term surveillance programme designed to monitor the efficacy of influenza vaccines and study the prevalence of influenza and other respiratory viruses among horses in Britain. Inactivated influenza vaccines were found to be effective in protecting horses from disease caused by influenza A/equine-1 but were less successful in protecting horses against influenza A/equine-2. The paper presents the clinical, epidemiological virological and serological findings obtained between 1971 and 1976.


Host factors and susceptibility to influenza A infection: the effect of ABO blood groups and HL-A antigens. The effect of two host genetic factors on the outcome of influenza A infections has been examined, ABO blood groups and HL-A antigens. A significantly higher proportion of blood group B subjects was found to have serological evidence of infection with epidemic influenza despite a high incidence of residual antibody among the volunteers. No difference was observed in the ability of subjects of different blood groups to seroconvert after receiving two doses of live attenuated influenza A vaccine, but a significantly higher proportion of blood group A vaccines seroconverted after receiving their first dose of vaccine. The association between HL-A type BW16 and resistance to infection with influenza could not be confirmed. The results are discussed in terms of an indirect association between susceptibility to influenza infection and the two host genetic factors.


A three-year evaluation of four commercial equine influenza vaccines in ponies maintained in isolation. Ponies held in isolation for 40 months were vaccinated and revaccinated with four commercial equine influenza vaccines. Little or no HI antibody was detected after the first inoculation; second and subsequent annual revaccinations produced peak HI antibody titres between 7 and 14 days. Titres fell quickly between 14 and 28 days and less quickly thereafter. The decline of HI antibody appeared to be related more to the initial titre attained and to the period after vaccination than to the composition of the vaccine. The response to a first annual revaccination was superior to that produced by a second annual revaccination. Ether-treated antigens were required to identify primary and secondary responses to the equine-2-component of vaccines.


Antibody formation in laboratory animals after parenteral application of A/swine influenza virus. Antigenicity of swine influenza viruses, Ann Arbor/31 and recombinant X-53, was compared on the different animal species. The serological investigations of animals infected with live or immunized with the inactivated virus, demonstrated a close antigenic relationship between the H and N antigens of both viruses. For inactivated vaccine preparation it was recommended, on the basis of our results, to use Ann Arbor virus instead of virus X-53.


A mouse model of influenza protection.

A mouse model of influenza protection. A mouse model has been developed in order to examine the parts played by humoral and cellular mechanisms in influenza immunity. Protection is assessed in terms of the amount of virus detectable in the lungs within 48 h of challenge. This system has two major advantages over the more common mouse lethality models. It is no longer necessary to use a mouse-lethal strain of virus; and protection is measured within days rather than weeks of challenge. Thus it is possible to determine the ability of the immune system to limit infection at an early stage, as distinct from curing a pre-existing infection and so preventing death. Transfer of spleen cells from an immune donor to a normal recipient will significantly reduce the amount of virus found in the lungs 24 h after challenge. The transferred cells are, however, capable of producing significant serum levels of anti-influenza antibody. Administration of serum from immune mice to normal recipients also results in a significant degree of protection within 24 h of challenge. These results give additional evidence that in the mouse significant protection is provided by serum antibody very soon after infection, but do not exclude the possibility that a part may be played by other mechanisms.


Polyacrylamide gel electrophoresis of the RNAs of new influenza virus strains: an epidemiological tool. Recently, we have shown by separating the RNAs and proteins of different influenza A viruses on polyacrylamide gels, that influenza A viruses contain 8 genes corresponding to 8 virus specific proteins. By analyzing the RNA patterns and the protein patterns of different recombinant viruses we, subsequently, succeeded in establishing a complete genetic map for influenza A viruses. These techniques were extended to characterize the genome of new influenza virus isolates. Thus it was found that the human isolate A/Wi/263/76 and the two swine virus isolates, A/swine/Wi/49/76 and A/swine/Wi/50/76 possess identical RNA patterns, which differ from the RNA patterns of other recent swine virus isolates. The human (Wi/263) and the two animal isolates (Wi/49 and Wi/50) were obtained on the same farm suggesting that the animal virus was transmitted from swine to man. This proves that swine viruses may occasionally infect humans without causing a pandemic. A comparative analysis of the different RNA patterns of other swine influenza viruses isolated around the same time at different locations and of those of recent human isolates showed that our polyacrylamide gel technique is a valuable epidemiological tool to identify and and characterize different influenza virus isolates.


Antigenic variation of influenza viruses isolated from the recent epidemics. In the winters of 1975-76 and 1976-77 there were fairly heavy epidemics of influenza in Japan, and on those occasions considerable discussions were held on the efficacy of influenza vaccine in connection with the variability of antigenic structure of the influenza virus. The type of the virus which prevailed in the winter of 1975-76 belonged to type A, but detailed antigenic analysis revealed that there had been two main antigenic types somewhat but definitely distinguishable from each other, the one is the well-known A/Victoria/75 type while the other is A/Tokyo/75 type. This epidemic seems to have started with the latter type, but soon the two types of virus prevailed hand in hand until the late part of the epidemic when the type A/Victoria/75 became overwhelming. The virus for the vaccine was however A/Tokyo/6/73 for that season, which is antigenically considerably different from both of these two strains. In the beginning of 1976, namely at the end of the epidemic season of type A, a few scattered epidemics due to type B influenza were reported from some parts of Japan. The result of antigenic analysis found that the virus belonged to B/Hong Kong/72 type, though showing some degree of antigenic schift. The same type of virus caused the epidemic of the winter 1976-77, which was considerably wide-spread and developed unexpectedly large number of cases. There were active discussion on the effectiveness of vaccine, of which B type was B/Gifu/1/73, recovered from the fairly large epidemic in 1973, and belonging to B/Hong Kong/72.


Serological surveillance of influenza in Hamburg and Munich (1976/1977). A monthly serological survey (HI-test) of influenza infections was done in Hamburg (1083 sera) and Munich (955 sera) between June 1976-February 1977 in order to find out if environment influences the host's response to infection. A higher frequency of seropositive reactions and percentage of protective antibodies (titer 1:40 and over) was found in the population of Hamburg versus Munich. The frequency was greater in individuals over 60 years (group IV) followed by persons 25-29 years (group III) than group II (15-24 years) and group I (0-14 years). There was no difference in the percentage of seropositive reactions within the 4 age groups from Munich. The GMT values of influenza antibodies in both populations studied followed the same pattern. Antibody titers against influenza antigens were found in decreasing order: A/Victoria 3/75, A/England 23/76, A/Port Chalmers 1/73, A/New Jersey 8/76, B/Hong Kong 8/73. The possible influence of climate on the host's response is discussed.


Influenza activity in metropolitan Rome, Italy, during the cold-weather months of 1976-1977. Several prospective methods for surveillance of influenza are systematically carried out among the population of this city: (a) monitoring of excess deaths from respiratory and other causes; (b) monitoring of excess absenteeism from work; (c) attempts to cultivate influenza virus from throat swabs obtained from patients with respiratory diseases attending outpatient services; (d) checking of increased antibody reactivity for prevailing influenza virus strains in serum samples obtained from healthy adults of the open population. The results of these studies will be reported with respect to influenza activity in the metropolitan area in the winter of 1976-1977. Comparison of the speed and effectiveness with which the influenza epidemic was identified in the urban population by the various surveillance methods will also be given.


Monitoring of influenza in Israel 1976/77. The main objectives of the monitoring were: (1) to define the prevalent virus involved in influenza activity: (2) to determine the time of its occurrence; and (3) to evaluate its extent and impact. A sudden rise in the frequency of visits associated with acute respiratory conditions in the age group 0-14 to the emergency rooms of 14 hospitals throughout the country, correlated well with the start of influenza B/Hong Kong activity; this was simultaneously attested by two different laboratories. The later and sporadic occurrence of influenza A/Victoria activity did not affect the usual trend observed in the frequency of visits to emergency rooms. An age group stratified serologic follow-up pointed to a progressively increasing rate of influenza B infection up to the age group 15-24. A crude morbidity rate of 13-18% was recorded during influenza B outbreaks in several agricultural settlements. The percentage distribution of cases was about 15,21, 26 and 37 in the age groups 0-4, 5-9, 10-14 and 15+, respectively. The mortality associated with influenza B and influenza A activity did not exceed the expected rate.


Properties of A/Victoria/3/75 recombinants: development of an attenuated strain RIT 4050. An attenuated Influenza A strain, RIT 4050, has been selected among the inhibitor resistant variants of a range of H3N2 recombinants of A/PR/8/34 and A/Victoria/3/75. The criterion used for the selection of the vaccine strain was the homology rate of the viral RNA of the recombinant with the complementary RNA of A/PR/8/34 as determined by an RNA-RNA hybridization technique. Safety has been assessed by administering the vaccine by the nasal route to double seronegative volunteers. Incidence and nature of post-vaccinal symptoms was low and mild as in healthy seropositive volunteers. The excretion pattern of the strain was investigated. Volunteers shed virus for one day after vaccination and the titre of the virus was low. Eight reisolates of RIT 4050 were characterized and found similar to the original vaccine strain offered to the volunteers.


Influenza viruses from avian and porcine sources and their possible role in the origin of human pandemic strains. Studies on influenza viruses from feral ducks trapped in Canada in August 1976, gave a 26% isolation rate from cloacal samples of juvenile birds. Several different influenza A viruses were isolated, some of which possessed novel hemagglutinin and/or neuraminidase antigens. Influenza A viruses isolated from the rectum of feral ducks replicate in the upper respiratory tract and also in the intestinal tract of feral and domestic ducks. Representative human influenza viruses of the H0N1, H3N2 and Hsw1 N1 subtypes replicate in the upper respiratory tract of ducks but not in the intestinal tract. The A/Hong Kong/68 [H3N2] influenza virus that has not been isolated from man for several years was recently isolated from pigs originating from The People's Republic of China. A/Victoria/3/75-like influenza viruses that are currently circulating in man were also isolated from pigs. Both the A/Hong Kong/68 and the A/Victoria/75-like viruses transmitted readily from pig to pig in experimental studies. The susceptibility of ducks and pigs to infection with human influenza viruses suggests that these animals may play an important role in the ecology of influenza A viruses.


Antigenic subgroups of influenza A (Hsw1 N1) virus differentiated by hemagglutination inhibition. Eleven influenza A/swine virus strains could be arranged in three subgroups by hemagglutination inhibition (HI) titrations. The antisera used include post-infection ferret sera (native as well as after adsorption with heterologous Hsw1 N1 virus) and paired human sera from recent influenza A patients, showing antibody titre rises against A/swine virus. For serological detection of infections with an unknown A/swine virus, virus strains of the subgroup with the broadest reactivity are more suitable than other strains. This subgroup comprises A/swine/1976/31, A/New Jersey/8/76 and A/X-53. The same will hold for vaccine strains.


Isolation from birds of influenza viruses with human neuraminidase. Attempts at virus isolation from cloacal swabs resulted in the recovery of 10 strains of hemagglutinating viruses from a total of 349 ducks, mainly shelducks (Tadorna tadorna) captured in the north of France. Four of these isolates were identified as influenza strains corresponding to the following antigenic composition: Hav6-N2, Hav6-Nav4 and Hav1-N2 (2 strains). Shelduck is known to be a partially migratory species, wintering in western Europe, some of them migrating northward to Scandinavia during the summer. The captures were made between November 1976 and February 1977: one of the birds was caught four times and was found to be negative for virus in November, positive in December (isolation of a strain Hav6-Nav4), negative again in January and February. Blood taken in February did not show the presence of HI antibodies to the homologous virus.


Rapid enzymologic anti-neuraminidase antibody microtest. A micro-neuraminidase-inhibition-technique (the Essen NIT) using a glycoprotein as substrate and employing the method of Aminoff for the determination of free N-acetyl neuraminic acid has been developed by our group. The main difference between the micro NI-test and the WHO-method is the mathematical evaluation of AB titer (TI 50) from the investigation of a single dilution only. This procedure is possible, because it could be proved that this reaction follows enzyme-antienzyme kinetics of the Michaelis-Menten type. On the basis of the microliter system and the Michaelis-Menten reaction, the Essen-NI-test has the following economical and technical advantages over the WHO-method: (a) use of only 1/25th volume of the expensive substrate (glycoprotein) per serum in comparison to the WHO-test, (b) investigation of up to 90 sera per technician and day instead of a few sera per technecian and 2 days and (c) testing of nasal washings without further dilution. Regression analysis of test results of antibody determination evaluated with both methods showed a linear correlation with a regression coefficient of about 1. Titers with the WHO-method were 5-10 times higher than with micro NI test, most possibly due to the shorter reaction times. Nevertheless, positive sera were found positive with either test. Strain specificity of neuraminidase could be equally well evaluated with the WHO-method and the Essen-NIT when 5 influenza virus A isolates from Berlin of 1968-1975 were tested against influenza virus X/15 HK immune serum.


Serological and virological investigations fo orthomyxovirus in birds in South-East Asian area. We have previously reported that some species of migrating ducks (pintail, mallard, widgeon and falcated teal) possess in their sera antibodies against H antigens of human or avian influenza viruses. Such findings have also been reported from other workers, and the appearance of new types of influenza viruses accompanied by outbreaks of new influenza pandemics, or circulation of influenza virus antigens in animals, birds and humans have been discussed on the basis of such findings. Recently a number of orthomyxoviruses have been isolated from wild birds such as myna, banded parakeets, etc. imported from India and some areas of South-East Asia. Some of them have H antigens not recognized previously, and some are found to have more or less common reactions with human H3 antigen, and consequently antigens Hav 7 and Heq 2, which are known to show cross-reaction with H3. The significance of such a fact in connection with the appearance of a new influenza pandemic is discussed.


Neuraminidase antibodies in serum and nasal washings after immunization by means of live and killed whole virion, split virion and subunit (HA and N) influenza vaccines. Anti-neuraminidase antibody (ANAB) formation was determined in serum and nasal washing fluids pre- and post-vaccination in 278 adult healthy volunteers vaccinated with different types of current experimental and conventional influenza vaccines. The best systemic ANAB formation expressed as conversion rate (CR) was observed with the subunit vaccine "Sandovac" (CR = 90%) followed by the split virion vaccine "Begrivac S" (CR = 66%), the whole virion vaccine "Alorbat" (CR = 65%) and the live attenuated vaccine "Alice" (CR = 58%). The best local ANAB formation was obtained with live attenuated vaccines (CR = 47-50%) followed by "Begrivac S" (CR = 34%) and "Alorbat" (CR = 17%). The subunit vaccine, unfortunately, could not be tested for ANAB formation. On the basis of this data the optimal method of immunization against influenza would consist of simultaneous topical and parenteral application of live attenuated and inactivated subunit or split vaccine.


Field study with a live influenza vaccine (RIT 4050) in children. In autumn of 1976 a study was performed with Gripovax (RIT 4050) in 126 schoolchildren in Vienna. Sixty-one of the children were 10 to 14 years old and 65 were 7 to 10 years old. The study was initiated in the older group (10-14 years old) by transnasal administration of a single dose of vaccine; 23 children received a second dose 7 days later. Symptoms were recorded daily up to the 7th postvaccinal day. 53 out of 61 vaccines did not report any symptoms during the 7 day postvaccinal period. 8 complained of mild and transient nasal stuffiness and only 1 child had a rise in temperature (37.8 degrees C). In a second group (7 to 10 years of age), 65 children received 2 doses of the vaccine at a 7 day interval. No symptoms were recorded in 57 subjects and only 8 reported mild and transient nasal stuffiness. Hemagglutination inhibition (HI) antibody titers were determined before and after vaccination. In the older age group (10-14 years), after one dose of vaccine (vaccinees with prevaccinal titers less than 1:20), seroconversion occurred in 20 out of 28 (71.4%) and after two doses, in 18 out of 21 (85.7%). Children aged 7 to 10 years received both doses of the vaccine. In subjects with prevaccinal titers less than 1:20, seroconversion occurred in 40 out of 43 (93%). Geometric mean of titers (GMT) before and after one dose was 24.3 and 97.4, respectively. The GMT of those children who received two doses (both age groups) was 30 preceding and 185 after vaccination.


Experiments in the preparation of live influenza B vaccines. A study is described of the selection of influenza B virus recombinants. Three virulent viruses isolated in 1970, 1970 and 1973, were crossed with host-range mutants of low virulence for man, which had originally been isolated in 1940, 1959 and 1956, respectively. Nine presumptive recombinants were inoculated into volunteers with low initial HI antibody titres. Although a number proved attenuated and there was evidence of high frequency of recombination, antigenic characterization of neuraminidases proved difficult. There was always some crossing between parental surface antigens, and appropriate antigenic hybrids for preparation of reference antisera were not available. Comparative virus titres at 33 degrees C and 38 degrees C were of limited value as a genetic marker. It is suggested that biological methods are unsatisfactory for the study of influenza B virus recombinants, and should be replaced by biochemical techniques designed to trace the parental origins of individual RNA segments.


Influenza A virus and its influence on the outcome of pregnancy in the mouse. The effect of sub-lethal doses of influenza A strains WSN (H0N1), MEL (H0N1) and MRC-7 (H3N2) administered intranasally during pregnancy was studied in C3H inbred and Prince Henry outbred mice. Maternal and neonatal mortality rates were significantly increased by infections in the last third of the gestational period. Infection with influenza strain WSN in the last part of the first third of the gestational period significantly depressed the growth rate of neonates. No evidence of viraemia, transplacental transmission or congenital malformations were observed. Invasion of alveolar spaces by mononuclear phagocytes and erythrocytes was more pronounced in pregnant mice infected in the last third of the gestational period than in non-pregnant mice, and paralleled an ablation of cell-mediated immune responsiveness.


Live attenuated influenza vaccines in young seronegative children. Seronegative children undergoing primary infection sensitively reflect the residual virulence of an experimental attenuated respiratory vitral vaccine. Two temperature sensitive (ts) A/Hong Kong influenza vaccines derived following chemical mutagenesis of a cloned stock of A/Great Lakes/65 have been evaluated in vaccine trials in seronegative children. The two vaccines, ts-1[A] and ts 1[E], differ in their laboratory characteristics. Ts-1[A] has a lower shut-off temperature, 37 degrees C vs 38 degrees C, and more limited replication in the Syrian hamster model system than ts-1[E]. In A/HK seronegative adults ts-1[A] is noninfectious whereas ts-1[E] will replicate and induce an antibody response. The genetic lesion of ts-1[A] was stable in the young child; in contrast, late in the course of virus shedding, ts-1[E] exhibited genetic instability with 4 individuals shedding virus which had lost the ts marker. Transmission to controls was rare with both vaccines being observed in only 1 of 5 controls with ts-1[A] and none of six controls with ts-1[E]. There were no respiratory symptoms associated with ts-1[A] vaccine virus shedding. Ts-1[E] virus shedding had a suggestive association with fever and cough in the seronegative child. The trials in seronegative children extent and confirm the inherent differences between ts-1[A] and ts-1[E] vaccine strains and support the concept that laboratory markers of attenuation are predictive of vaccine behavior in the seronegative child.


Further researches on live influenza virus vaccines. A/Port Chalmers 1/73 and A/Victoria 3/75 live vaccines were well tolerated after oral administration and showed good immunogenic properties in subjects devoid of immune-defence or having low antibody titer. A/Victoria 3/75 vaccine was prepared before the epidemiological appearance of the corresponding virus which demonstrates that the preparation of a vaccine with new strains can be made in a comparatively short time. Our experiments and controls allow us to establish that the oral administration of influenza virus, grown on chicken kidney embryo, elicits the appearance of HI antibodies in a high number of susceptible subjects. A 60% seroconversion rate obtained after administration of two doses represents a favourable result, the more so as the vaccine can be considered absolutely safe in very young subjects.


[Benign cutaneous lymphadenosis (Bäfverstedt's disease) of the nipple (author's transl)]. Benign circumscribed cutaneous lymphadenosis of the areola of the nipple (Bäfverstedt's disease) occurs in children and adults. We observed 11 cases: 3 men, 3 children and 6 women. The areola undergoes rapid swelling and becomes red. At times the nipple itself is included. Unilateral enlargment and distortion of the nipple area becomes apparent. Sometimes this is associated with a tumor-like infiltration of the retro-mammillary tissue. In Contradistinction to Pagets disease of the nipple and to a mammillary adenoma there is no eczema and no ulceration. The clinical features and the typical pruritic course establish the diagnosis. Healing is spontaneous, but protracted. The aetiology is probably of an inflammatory nature. Treatment with short courses of antibiotics and anti-inflammatory agents resulted in a faster reduction of the cutaneous signs and corroborated the clinical diagnosis. We consider surgical treatment as unnecessary because circumscript benign lymphadenosis of the nipple area has a harmless course.


[First results with a new prostaglandin E2-derivate (author's transl)]. A new tissue-selective prostaglandin E2-derivate, 16-Phenoxy-prostaglandin E2-methansulfonamide (SH B 286) developed by Pfizer, USA, and Schering, Germany, has been investigated as abortifacient using the intrauterine as well as intravenous route of application. Vital signs, intrauterine pressure, serum levels of steroid hormones, hPL and hCG were recorded before, during and after administration of Pg SH B 286. By using 100--250 microgram Pg SH 286 extraamniotically abortion rates reached 80%. Severe systemic effects did not occur. Uterine cramps (40% of the women), nausea (23%) and vomitus (15%) were tolerable and needed rarely medication. The intravenous administration of Pg SH B 286 has been investigated for the first time with three dosis regimens. 33 of 38 women had complete abortion with dose-dependant side effects and without severe complications. The low dosage schedule (0,5--1,5 microgram/ml, total approx. 1000 microgram) had the same efficacy rate as the higher ones and was associated with the lowest systemic side effects. Premedication with analgetics was not necessary. Pg SH B 286 caused a marked increase of intrauterine pressure inducing abortion. If the measured decline of steroid hormones--mainly progesterone--contributes to the abortifacient efficacy of this prostaglandin is yet unsolved. The clinical usefulness of Pg SH B 286 has been demonstrated by our study.


[Communicating uteri; a rather uncommon but important malformation (author's transl)]. A rare genital double malformation is dealt with in short. Including the four cases, which are reported, the number of the known cases in the literature amounts to only 31. The characteristic feature of the malformation is a communication of embryological origin between two uterine cavities. Diagnostic difficulties and clinical peculiarities can arise. Very often the genital malformation is accompanied by unilateral agenesis of kidney and ureter. Some clinical symptoms cannot be recognized and treated without knowledge about the existence of communication uteri, but the knowledge that malformations of the urinary tract may coexist is not less important. Indeed, it may be crucial for the patient's destiny.


[Clinical problems, therapy and prophylaxis of primary carcinoma of the fallopian tube (author's transl)]. 31 cases of primary carcinoma of the fallopian tube from 1960 to 1976 are reported. All these patients underwent operative treatment at the 1st University Clinic of obstetrics and gynaecology of Vienna. 8 out of 23 patients survived for more than 5 years. The evident advantage of a complete operation with post operative telecobalt radiotherapy for the results of 5-years-survival is shown. The possibility and necessity of prophylaxis of carcinoma of the fallopian tube by extirpation of both fallopian tubes in any case of hysterectomy are emphasized.


[The advantages of the extra-amniotic transcervical instillation of rivanol in therapeutic abortions (author's transl)]. Our experience with the transcervical extra-amniotic instillation of 70 ml 0.1% Rivanol solution in 154 cases of first trimestre, second trimestre abortions and intra-uterine fetal deaths is reported. This simple and safe method has several advantages which render it suitable for out-patient usage should the rate of therapeutic abortions increase even more. The gentle dilatatory effect on the cervix is remarkable and is noticeable after 24 hours. Dilatation with the Hegar-dilators becomes unnecessary. There were no major complications. The stress on the patient is minimized.


X-ray-induced chromosome aberrations in mouse dictyate oocytes. II. Fractionation and dose rate effects. Slit-dose experiments were done on maturing dictyate oocytes to determine if the magnitude of the first dose influenced the "rejoining time" of radiation-induced chromosomal lesions. A total dose of 400r was split into various combinations with varying fractionation intervals. The data derived from analyzing interchanges indicate that there is no difference in the rejoining time whether the first dose was 100, 200, or 300r. It thus appears that the radiation dose in the ranges studied does not significantly alter the rate of repair of the chromosomal lesions. This conclusion is contrary to that which has been propounded to explain the nonlinear dose curves obtained for specific locus mutations. Chronic 60Co gamma-ray exposures were given to female mice over an 8-day period. The exposures were delivered during the period of peak sensitivity, i.e., 8-16 days prior to ovulation. The doses given were 117, 240, 348, and 483r. The aberration yields observed were dramatically lower than for comparable doses of acute X rays even when the RBE of gamma rays compared with X rays is taken into account. The large drop in yields at the low dose rates is interpreted as resulting from a large two-track component in the acute curve, and as being independent of effects on repair systems.


The genetics of alpha-hydroxyacid oxidase and alcohol dehydrogenase in the mouse: evidence for multiple gene loci and linkage between Hao-2 and Adh-3. Electrophoretic polymorphisms for stomach alcohol dehydrogenase (ADH-C2) and kidney L-alpha-hydroxyacid oxidase (HAOX-B4) have been identified in an Asian subspecies of mouse, Musmusculus castaneous. These variants are inherited in a normal Mendelian fashion with two alleles in each case showing codominant expression. The structural gene loci for those enzymes (Adh-3 and Hao-2, respectively) are apparently linked (17.6% recombinants) in this organism, whereas the multiple gene loci for HAOX, Hao-1 (encoding the A4 liver isozyme) and Hao-2, exhibited independent segregation and are unlinked (50% recombinants). Evidence is presented for 3 ADH loci: ADH-1, encoding liver ADH-A2 which exhibits high activity with ethanol (SELANDER, HUNT and YANG 1969; ADH-2, liver and stomach ADH-B2 using 2-hexene-1-ol as substrate; and Adh-3, stomach ADH-C2 using both benzyl alcohol and 2-hexene-1-ol as substrate.


Fitness effects of EMS-induced mutations on the X chromosome of Drosophila melanogaster. II. Hemizygous fitness effects. X chromosomes mutagenized with EMS were tested for their effects on the fitness of hemizygous carriers. The tests were carried out in populations in which treated and untreated X chromosomes segregated from matings between males and attached-X females; the populations were maintained for several generations, during which time changes in the frequencies of the treated and untreated chromosomes were observed. From the rates at which the frequencies changed, the fitness effects of the treated chromosomes were determined. It was found that flies hemizygous for a mutagenized chromosome were 1.7% less fit per mM EMS treatment than those hemizygous for an untreated chromosome. Since the same flies were only 0.5% per mM less viable than their untreated counterparts, the total fitness effect of an X chromosome carrying EMS-induced mutants is three to four times greater than its viability effect. By comparing the heterozygous effect of a mutagenized X chromosome on fitness with the corresponding hemizygous effect, the dominance value for the chromosome is estimated to be about 0.25.


Properties of equilibria in multi-locus genetic systems. The classical mathematical theory of population genetics considered, for simplicity, almost exclusively one-locus systems. In the last two decades much work has been done on two-locus and, less frequently, multi-locus systems. This research has usually involved investigating properties of systems with given, and usually rather special, fitness parameters. Real genetic fitness systems are undoubtedly multi-locus and seldom will possess simplifying characteristics. One aim of this paper is to study generalized systems where no special assumptions are made about fitness structure, the number of alleles at each locus, the number of loci involved or the recombination structure between loci. A second aim is to consider marginal properties (often one-locus properties) of complex systems: the fact that many observations involve data from only on locus makes this second aim relevant.


Effects of life-long dietary protein restriction on mortality, growth, organ weights, blood counts, liver aldolase and kidney catalase in Balb/C mice. Certain types of nutritional restriction can prolong life in mammals. This investigation documents life long effects of five protein diets in 1,000 Balb/c male mice. Balb mice subjected to 4% protein (lowest) diet had life expectancy that was marginally significantly prolonged when compared with control mice fed 24% protein (highest) diet. Body and organ weights of protein restricted mice generally were less than control mice. No significant differences among diets were found with blood counts, protein concentrations of liver and kidneys, or kidney catalase activity. Kidney catalase activity fell with age. Liver aldolase was induced by dietary sucrose, and aldolase fell with age in protein restricted mice, but not in controls.


Changes in growth hormone status related to body weight of growing cattle. The growth hormone (GH) status of 24 castrated male cattle was studied over a range of body weights by measuring GH in the blood plasma and anterior pituitary and by calculating metabolic clearance (MCR) and secretion rates after injection of GH. As the cattle increased in size, pituitary weight and GH content, MCR of GH and secretion of GH decreased relative to body weight. Plasma concentrations of GH did not decrease as markedly as secretion because MCR/body weight was also lower in the larger animals. At all sizes, more than 99% of the total GH in the body was located in the anterior pituitary. It was calculated that the pituitary releases 0.58% of its GH content per hour. This rate of release did not significantly change with body weight. It is suggested that basal secretion of GH by the anterior pituitary is related to GH content and that, as animals grow, there is gradually less GH available per unit of body mass.


Changes in RNA, DNA and protein content and the rates of protein synthesis and degradation during hypertrophy of the anterior latissimus dorsi muscle of the adult fowl (Gallus domesticus). Hypertrophy of the anterior latissimus dorsi muscle of the adult fowl was induced by attaching a weight to one wing and after 2, 6 and 14 days the muscle wet weight, as well as protein, RNA and DNA contents were measured. After 6 days of hypertrophy the wet weight of the muscle had increased by 74%, the protein content by 44%, RNA by 203% and DNA by 83% compared with the contralateral control. Average rates of protein synthesis and degradation were measured over the 14 days of hypertrophy from the rate of loss of radioactivity in the muscle protein after pulse labelling using 3H-leucine. Results were compatible with a 50% increase in the protein synthesis rate with no detectable change in the degradation rate. The increase in synthesis rate was paralleled by a similar rise in the RNA concentration. The DNA content indicated that this increase in RNA resulted from an increased RNA production per nucleus as well as from an increased number of nuclei. The kinetics of the loss of total radioactivity from the muscle protein and the amount of free 3H-leucine remaining in the muscle free amino acid pool during hypertrophy indicated that reutilization of 3H-leucine was extensive. This was in spite of attempts aimed at minimizing reutilization by feeding fowls a high protein diet plus a daily supplement of unlabelled leucine.


Serum hormones in the perinatal pig and the effect of exogenous insulin on blood sugars. Growth hormone (GH), insulin, cortisol, triiodothyronine (T3) and thyroxine (T4) were determined in serum of fetal pigs at 90, 100, 110 and 114 days of gestation and of newborn pigs at 1 and 24 hours of age. Fetal GH, T3 and cortisol increased between 90 and 110 days. GH concentration decreased between 110 and 114 days, while T3 and cortisol were unchanged. T4 was variable in fetal pigs and no relationship with T3 levels was apparent. Fetal insulin was constant at approximately 10 muU/ml. In newborn pigs there was a 3-fold and 2-fold increase in T3 and T4, respectively, during the first 24 hours of life. Cortisol in serum more than doubled during the first hour. Between 1 and 24 hours, there was a simultaneous decrease in cortisol and a 6-fold increase in insulin. No significant change in GH was noted during this time. Intraperitoneal insulin injected one hour before sacrifice induced a hypoglycemic response in newborn pigs, but not in fetal pigs.


Stages in the emergence of the dentition: an improved classification and its application to Israeli children. An improved classification of dental development according to the eruption sequence of morphological dental classes is presented. The definitions ensure that the stages are mutually exclusive and permit a clear estimate of all developmental sequences. The age distribution for each dental stage, investigated for a sample of 2116 Israeli children, was found to be normal with a small but systematic skewness; this could reflect the greater variability in age at which children leave a dental stage than at which they enter it. All dental stages initiate and terminate earlier in girls. The sequence of emergence of permanent teeth is virtually identical in both sexes except for the canines. Maxillary and mandibular incisors and canines erupt somewhat later than those in other populations.


Applicability of some of the assumptions used to estimate the weight of the skeleton in the growing pig and beagle. Assumptions used in indirectly estimating skeletal weight were tested on 55 pigs (ages day 0-week 12) and 42 beagles (ages day 0-1 year). One of the assumptions was that skeletal weight constitutes a constant proportion of lean body mass (fat-free wet weight). In the beagle the skeletal weight was not constant, but a decreasing proportion of LBM during growth. In the pig there were no significant changes comparable to those in the beagle, probably because only a small part of the growth period was studied. Also, the assumption that bone mineral was 65% of fat-free dry weight of the skeleton was not applicable to the beagle, where it increased from 55% (day 0-week 12) to 70% (mouth 4-1 year). In both species skeletal growth was a function of total fat-free dry weight (FFDWt), but in the beagle the ratio Kt/FFDWt increased from 130 (day 0-week) 12) to 160 (month 4-1 year) and reflected changes in the contribution of body cell mass and skeletal to FFDWt.


Estimation and testing of parameters in Richards growth model for western grebes. Growth rate coefficients for dark- and light-phase western grebes (Aechmophorus occidentalis) are compared with the Richards' growth model. The statistical assumptions necessary to estimate and test parameters are carefully scrutinized. Autocorrelations of the residuals are removed with an autoregressive model, and heterogeneity of variance of the residuals is corrected with weighted least squares. A model allowing random variation in the process of growth is also suggested as being a more realistic representation of the process. No differences were detected between dark- and light-phase growth rate coefficients.


The perinatal rat: body weight, hematocrit and regional changes in heart weight and lactate dehydrogenase isozyme composition and activity. Body weight (BW), hematocrit (Hct), heart weight (HW) and cardiac lactate dehydrogenase (LDH) activity and isozyme pattern were studied in the perinatal rat. BW increased linearly, from 5 days before birth till 10 days after birth, while Hct increased from 30 to 34% within 1 day of birth. HW increased in step with BW. However, the relative contribution to total HW of right ventricle (RV), interventricular septum (S) and atria declined relative to the left ventricle free wall (LVW) beginning 2 to 3 days before birth. RV/LVW declined steadily throughout the study period. LDH specific activity in LVW, RV, S and atria increased greatly prior to birth and less so afterwards, with atria showing the lowest values throughout the study. Total LDH activity in each portion of the heart paralleled the respective regional weight changes. LDH isozyme composition (percent M subunit) declined at the time of birth in LVW, RV and S from 63 to 43%; change in atrial M subunit was smaller. The change in LDH isozyme composition could be accounted for in LVW, RV and S by increasing H subunit activity alone. In atria, both M and H subunit activity increased.


Potassium and magnesium depletion in patients with cirrhosis on maintenance diuretic regimens. Total body potassium (40K) and leucocyte potassium measurements were carried out on 19 patients with stable but decompensated cirrhosis maintained on diuretics for previous ascites. Of 13 patients receiving spironolactone alone none had a total body potassium below the expected lower limit of normal, whereas, of six receiving additional frusemide, two had low values. The results for leucocyte potassium were in agreement and simultaneous measurements of leucocyte magnesium showed a close correlation, those with intracellular potassium depletion also having magnesium depletion. One such patient was treated with magnesium supplements without effect on the potassium, although intracellular magnesium was improved. It is concluded that spironolactone alone is the treatment of choice in the maintenance management of such patients; that additional potassium would be unnecessary; and that additional frusemide should be avoided if possible.


Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure. Bile acid levels were measured in the sera, cerebrospinal fluid (CSF), and brain tissue of 10 patients immediately after death from fulminant hepatic (FHF). Serum bile acids in FHF were predominantly conjugated, and total bile acid levels were higher in all 10 patients than in normal controls (85.9 +/- SE 8.4 compared with 5.7 +/- 0.4 nmol/ml, P less than 0.001). Small but significant amounts could be detected in CSF (range 1.2-5.3 nmol total bile acid/ml) and brain biopsies (1.0-18.8 nmol/g wet weight) of FHF patients, whereas none could be detected in CSF and brain biopsies of patients dying without evidence of liver disease. There was no relationship between serum, CSF, or brain levels and duration of coma, or presence of cerebral oedema found in five FHF patients at necropsy. However, serum bile acid levels were similar in FHF to those found in chronic liver disease without encephalopathy and lower than those found to inhibit brain respiration in vitro. A primary role for these compounds in the pathogenesis of coma in FHF therefore seems unlikely.


Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis. The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3.02 +/- 0.69 (mean +/- ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic pancreatitis and carcinoma of the pancreas. In 18 patients with choledocholithiasis a raised ratio distinguished those with pancreatitis as assessed independently by the surgeon at laparotomy from those with a macroscopically normal pancreas. Raised Cam/Ccr ratios were also found in diabetics with ketoacidosis and in three patients with fulminant alcoholic liver disease. Though a positive correlation was found between the Cam/Ccr ratio and serum creatinine concentration, abnormally high ratios did not occur in 30 patients with chronic renal failure. A significant increase in Cam/Ccr ratios was produced in six healthy volunteers by intravenous injection of glucagon. However, it is unlikely that hyperglucagonaemia alone accounts for the increased Cam/Ccr ratio seen in acute pancreatitis, as no correlation was found between the clearance ratio and the plasma glucagon concentration in a series of patients. In two other patients in whom excess circulating pancreatic polypeptide was detected the Cam/Ccr ratio was normal. It is concluded that, in view of the sensitivity and relative specificity of finding an increased Cam/Ccr ratio in acute pancreatitis, its determination should be valuable clinically, especially in those cases of hyperamylasaemia where the cause is in doubt. The mechanism whereby the ratio is increased is unknown, and it is unlikely that either glucagon or pancreatic polypeptide is a major factor in its production.


Somatostatin therapy of acute experimental pancreatitis. Because somatostatin (SRIF) reduces exocrine pancreatic secretion, its effect on acute pancreatitis was investigated in rats. Linear SRIF reduced serum amylase and lipase but had no effect on pancreatic necrosis, oedema, leucocyte infiltration, and enzyme content. The mortality rate was not reduced. These results do not recommend the use of SRIF in the treatment of acute pancreatitis.


Effect of carbenoxolone sodium on human gastric acid secretion. Neither basal nor peak acid output changed significantly after treatment for four weeks with carbenoxolone sodium as Biogastrone tablets in patients with gastric ulcer or Duogastrone capsules in patients with duodenal ulcer.


Gastric emptying of wholemeal and white bread. We studied the rates at which solid and liquid leave the stomach after meals of wholemeal and white bread by using a double isotope technique. There was no difference in the rates at which the solid phases of the gastric contents left the stomach but liquid left the stomach significantly more rapidly with white bread than with wholemeal bread. Furthermore, the amount of liquid leaving the stomach unaccompanied and therefore unbuffered by solid was significantly greater after while bread than wholemeal bread. These findings may be of significance in the pathogenesis of duodenal ulcer and they provide a rational basis for a possible form of dietary treatment.


Bile acid studies in uncomplicated Crohn's disease. The pool size and composition of bile acids were studied in 13 unoperated patients with uncomplicated Crohn's disease; 10 patients with ulcerative colitis, and 10 normal subjects. Many patients with Crohn's disease had in their bile a significantly increased amount of ursodeoxycholic acid. The bile acid pool size was significantly decreased and the ratio of glycine to taurine conjugates was significantly increased in the Crohn's disease patients. The reduction in bile acid pool size was related to the activity of the disease. The disorders of bile acid metabolism suggest that the intestinal involvement in Crohn's disease is much more extensive than can be demonstrated by careful radiological examinations.


14C-Glycocholate test in Crohn's disease--its value in assessment and treatment. The (14)C-glycocholic acid test ((14)C-GCA) has been assessed in 27 patients who have had resection of the ileum and colon for Crohn's disease and in 19 patients with unoperated stable Crohn's disease. The incidence of increased breath output of (14)CO(2) and faecal output of (14)C was significantly greater in operated patients. Half the unoperated patients had normal results and, of the others, a modest increase in faecal (14)C was the usual finding. There was no correlation between the (14)C-GCA test, the Schilling test, and the extent and severity of the radiological signs in the unoperated patients. Metronidazole therapy was poorly tolerated and had little or no influence on symptoms but did decrease the excretion of (14)CO(2) in the breath when the (14)C-GCA test was repeated. Cholestyramine therapy was beneficial in the majority of resected patients with diarrhoea and an increased faecal (14)C excretion and, on repeat testing, there was a significant increase in the output of breath (14)CO(2). The beneficial effect was less marked in the unoperated patients and the breath (14)CO(2) output remained normal in those retested. Interruption of the enterohepatic circulation of bile acids did not seem to make an important contribution to the symptoms of patients with stable unoperated (and uncomplicated) Crohn's disease, even when the ileum was extensively involved.


Humoral immune system in inflammatory bowel disease: I. Complement levels. Serum levels of complement components Clq, C4, C3, and Properdin factor B, from the classical and alternative pathways of complement activation, have been estimated in patients with ulcerative colitis and Crohn's disease. C3, factor B, and to some extent C4 concentrations all increased when the disease was active. In remission the levels of these components did not differ from hospital control patients. There was no evidence for the preferential consumption of the proteins of either pathway of activation, even in those patients with evidence of circulating immune complexes.


Adynamic bowel syndrome. Report of a case with disturbance of the cholinergic innervation. A case of adynamic bowel syndrome is described. Full thickness biopsies of the large bowel showed the presence of ganglion cells, no acetylcholinesterase positive nerves in the lamina propria, submucosa or among the smooth muscle cells of the circular and longitudinal muscle coats, and absence of the argyrophil plexus. Electron microscopic examination showed replacement of the normal axon bundle by vacuolated tracts with small round bodies in one area--probably viral. Neuronal cytoplasm also showed similar vacuolation. It is suggested that the damage to the cholinergic innervation may be caused by a neurotoxic agent.


Detection of antibody against limax amoebae by means of the indirect haemagglutination test. A detailed description is given of the procuedure of the indirect haemagglutination test employed in the detection of specific antibodies against pathogenic amoebae of the genera Naegleria and Acanthamoeba. The preservation of all ingredients obtained by lyophilisation provide for a standard pattern of the test. The results of the test with experimentally prepared immune rabbit sera demonstrate an antigenic uniformity of the various isolates of Naegleria fowleri, and their marked difference from Acanthamoeba.


Influence of breeding technology of helminth fauna of geese (Anser anser f. domestica). Two hundred goose broilers originating from farms with different housing facilities were examined for helminth parasites. The farm of the first technological type consisted of halls with deep liter without a run and that of the second type had grass runs neighbouring with a sheet of water. The geese from the first farm harboured A. galli, H. gallinarum and C. obsignata; those from the second farm, D. lanceolata, H. dispar, A. anseris and C. obsignata. In the first case, the geese were infected by helminths from chickens. The incidence and intensity of infection, frequency of single and mixed infections and relation between the incidence and intensity of infection and the age of broilers were evaluated. The influence of breeding technology on the formation of helminth fauna and the significance of individual helminth species in goose breeding are discussed.


Studies on digenetic trematodes of the genus Prosthodendrium Dollfus, 1931 from some Egyptian bats. 2. Trematodes of the subgenus Paralecithodendrium Odhner, 1911. A review of the subgenus Paralecithodendrium Odhner, 1911 is presented. Prosthodendrium (Paralecithodendrium) glandulosum (Looss, 1896) is redescribed from some Egyptian bats. The present study indicated that this species is a very variable one. Moreover, a new species P. (Paralecithodendrium) aegyptiacum is described from two species of bats.


Records of Cucullanus truttae (Fabricius, 1794) (Nematoda: Cucullanidae) from Swedish brook lampreys, Lampetra planeri (Bloch). Adult nematodes of the family Cucullanidae, parasitic in the abdominal cavity of the brook lamprey, Lampetra planeri (Bloch) from the River Stensån, south Sweden are described and illustrated. According to the morphometry, these nematodes belong to the species Cucullanus truttae (Fabricius, 1794)--a common intestinal parasite of salmonid fishes. The name Dacnitis stelmioides Vessichelli, 1910 is considered to be a synonym of the latter. The role of lampreys in the life-cycle of C. truttae is discussed: although lampreys are either intermediate hosts or serve only as transport hosts for larvae of this parasite, the nematode larvae can attain maturity in this host.


Experimental infection of foxes with Tahyna virus. Three foxes about 18 weeks old were each subcutaneously inoculated with approximately 200 LD50 dose of extraneurally passaged strain of the Tahyna virus "236". Viremia was demonstrated in all animals during the 48-96 hours interval after infection. The maximum value was 1.31 dex LD50/0.02 ml. Three weeks after infection a seroconversion was revealed by means of hemagglutination-inhibition test (from titre less than 1 : 10 to 1 : 320) and plaque-reduction neutralization test (from titre less than 1 : 4 to titre 1 : 4096 or 1 : 8192).


Fifty-day observation of a free-ranging adult male chimpanzee. An adult male chimpanzee living in Gombe National Park, Tanzania, was observed for 50 consecutive days during the 1974 dry season, for a total of 563 h. This individual, Figan, was the alpha male of a community of 42 chimpanzees. The composition and size of temporary associations within the community was influenced largely by the presence of one estrus female and by characteristics of the food resources. Figan's daily time budget varied little for travel and grooming, but there were major changes in time spent feeding tha inactive over the 50 days. Predatory behavior occurred periodically and meat was eaten on five occasions. Agonistic and sexual behaviors are discussed relative to Figan's high social status. A cooperative relationship was maintained between Figan and his older brother.


Intra-group variations in the dental eruption sequence of Macaca fuscata fuscata. The purpose of this investigation was to establish general trends of intra-group variations in the dental eruption sequence of a semi-wild troop of Maca fuscata fuscata. Dental impressions were taken on 128 animals of varying ages. The analysis of the dental casts revealed sexual dimorphism in sequence and timing of eruption.


Origin of acrocentric trisomies in spontaneous abortuses. A total of 33 spontaneous abortuses with various acrocentric trisomies were studied for the origin of the extra chromosomes using Q- and R-band polymorphisms as markers. Eleven trisomic abortuses were informative: nine trisomic abortuses (one with trisomy 13, three with trisomy 21, and five with trisomy 22 including one with a 46,XX/47,XX,+22 mosaicism) originated at maternal first meiosis; a 21-trisomic abortus resulted from an error at maternal second meiosis (or first mitosis); and a 13-trisomic abortus was of maternal first or second meiotic origin. The abortus with mosaic trisomy 22 started as a 22-trisomic zygote resulting from an error at maternal first meiosis, followed by a mitotic (in vivo or in vitro) loss of the paternally derived chromosome 22.


Investigations on the polymorphism of sperm diaphorase in man. Evidence for a third common allele, SD. The polymorphism of sperm diaphorase (SD) was investigated in 141 unrelated persons from Hessen, Germany, by high voltage thin-layer agarose gel electrophoresis (Age) and thin-layer isoelectric focusing on polyacrylamide gel (Pagif). In addition to the three known common phenotypes SD 1, 2-1, and 2, two further phenotypes with the preliminary designation SD 3-1 and SD 3-2 were discovered. This polymorphism can thus be explained in terms of three alleles, SD1, SD2, and SD3 segregating at an autosomal locus. The allele frequencies calculated from the five different phenotypes SD 1, 2, 2-1, 3-1, and 3-2 are: SD1 = 0.7553, SD2 = 0.2234, and SD3 = 0.0213. As we also found SD activity in female reproductive tract tissues (ovaries, oviducts, uterus), the term 'gonadal diaphorase' (GD) appears to be applicable.


Comparative investigations with trypaflavin in metaphase-II oocytes and in dominant lethal assay. Pregnant C3H mice were orally treated with 50 mg Trypaflavin/kg on day 7, 11, 14, or 15 post conception. The embryos were thus treated in utero with the test compound. At the age of 10 weeks, the dominant lethal assay was performed with F1 females. Dominant lethal mutations were induced only in those mice treated in utero on day 7 of the prenatal stage. Female C3H mice were chronically treated with Trypaflavin (50 X 2 mg/kg/day; dissolved in drinking water). These mice were caged with untreated males. The percentage of preimplantation egg loss and the yield of dead implants per female was increased. Female NMRI mice were chronically treated with Trypaflavin (50 X 2 mg/kg/day by stomach tube). In metaphases II of unfertilized oocytes, the yield of all observed aberration types (aneuploidies, gaps, satellite associations, breaks and fragments, deletions, and interchanges) was increased weakly.


Improved technique for electrophoresis of human galactose-1-p uridyl transferase (EC 2.7.7.12). A newly developed electrophoretic technique for human galactose-1-phosphate uridyl transferase confirms the multiple band patterns for the Duarte and Los Angeles variants. This represents the first confirmation for the Los Angeles variant. The observed frequencies of N, D, and LA types are similar to earlier reports for these variants.


Gene diversity in Indian populations.

Gene diversity in Indian populations. Gene frequency data of ten protein and enzyme loci in seven populations of India were collected from the literature. The gene differentiation among seven populations relative to total population was only 0.6%, indicating that the genic variation between populations was small compared to that within them. Using 29 common protein loci, the genetic distances between Indians and three major races of man, Caucasoids, Mongoloids, and Negroids were also determined. Indians are closer to Mongoloids than to Caucasoids or Negroids as indicated by the phylogenetic tree.


Ion binding properties in acetonitrile of cyclopeptides built up from proline and glycine residues. Ion binding properties of antamanide-like cyclopeptides cyclo-(Pro2-Glyn-Pro2-Gly m) (n,m=1-3) have been studies by CD spectroscopy and by conductivity measurements. Cyclo-(Pro2-Gly-Pro2-Gly) forming complexes of different stoichiometry can be characterized by a strong preference of selectivity for Mg++ and Ca++ ions over alkali ions whereas the other members of the series bind selectively alkali and alkaline earth cations with ion radius of about 1 A. Three main types of CD spectra of cyclic peptides and their complexes can be differentiated. Type I showing two negative Cotton effects at around 220 nm and 200 nm (Ib, Fig. 3), type II showing a positive band around 220 nm and a strong negative one below 190 nm (e.g. Ic in acetonitrile, Fig. 4), and type III showing a strong negative band in the 205 nm region (e.g. mental complexes of Id, Fig. 6).


Comparative conformational analysis of human choriomammotropin and somatotropin from several species. The conformations of porcine somatotropin and human choriomammotropin have been studied using circular dichroism (CD) and the results compared with spectra of human, murine, ovine, and bovine somatotropin. The far ultraviolet CD spectra of the six proteins were similar, and each spectrum was analyzed using constrained linear least squares. The following average percentages of alpha-helicity, beta-structure, and aperiodic (nonhelical) conformation were obtained: 57, 6, and 37, respectively, based on a standard protein reference set, and 42, 22, and 36, respectively, based on poly-L-lysine as reference. Thus, the estimated secondary structure is strongly dependent upon the reference data used. Interestingly for these similar proteins, it appears that over 60% of the residues are part of ordered secondary structure and less that 40% are in an aperiodic conformation. The near ultraviolet CD spectra of these hormones were similar in many respects, although certain significant differences were observed, particularly in the sign of various extrema. These spectral differences probably reflect non-identical microenvironments of the aromatics and disulfides, arising from differences both in amino acid sequence and local conformation.


Active esters in the formation of ester bonds between amino acids and polymeric supports. The imidazole catalyzed transesterification of active esters was used for the formation of the ester bond between the carboxyl group of protected amino acids and the hydroxyl group of a polymeric support applied in solid phase peptide synthesis. Anchoring of the C-terminal residue to the hydroxymethyl polymer proceeded smoothyl and provided a high degree of incorporation. No racemization was observed in the imidazole-catalyzed alcholysis. The procedure could be carried out with various active esters such as esters of o-and p-nitrophenol, 2,4,5-trichlorophenol, pentachlorophenol and N-hydroxysuccinimide.


Side reactions in peptide synthesis. V.A reexamination of the mixed anhydride method. Acylation of amino acid beta-naphthylamides with protected (Boc) amino acidisobutylcarbonic acid mixed anhydrides resulted in each case in the formation of some undesired by-product: an isobutyloxycarbonylamino acid beta-naphthylamide. The amount of this second acylation product was particularly high, with the hindered amino acids valine and isoleucine as carboxyl-components. The nature of the amino component had no major influence on the extent of this side reaction.


Human somatotropin 53. Synthesis and biological activity of the amino terminal fifty-four residue fragment. The amino terminal 54 residue peptide fragment of human somatotropin [Cys(Gam)53]-HGH-(1-54), has been synthesized by the solid-phase method. The symmetrical anhydride and active ester coupling methods were used exclusively. The synthetic product was purified by gel fitration isoelectric focusing, and partition chromatography. It was found to be homogeneous by six additional criteria. In complement fixation experiments the synthetic product was immunologically active with antisera to HGH and [cys(Cam)53]-HGH-(134). Antiserum raised against the synthetic product was immunologically active in the homologous assay and with HGH,[Cys(Cam)53]-HGH-(1-134), and [Cys(Cam)53]-HGH-(15-125). The synthetic fragment exhibited 53% of the activity of [Cys(Cam)53]-HGH-(1-134) in the rat tibia assay.


Hemoglobin Tak in a newborn Malay.

Hemoglobin Tak in a newborn Malay. The trait condition for hemoglobin Tak, was found in a 4-day old newborn Malay who suffered from severe neonatal jaundice. The beta chain of the abnormal hemoglobin was elongated by 11 residues at the C-terminus and had the same structure as reported for Hb Tak. The mother was heterozygous for this abnormal hemoglobin, the father was normal. The mother and child, 4 years later, did not show clinical or hematological symptoms except definitely increased resistance of their erythrocytes to hypotonic saline solutions and slight anisopoikilocytosis. The abnormal gene in the two reported Thai families and in our Malay family may have the same origin.


Hb M Milwaukee in a German family.

Hb M Milwaukee in a German family. The second occurrence of Hb M Milwaukee is reported in two members of a German family who had cyanosis since early childhood. Contrary to earlier reports, Hb M Milwaukee exhibits a distinct heat instability. It is suggested, that in this family the variant resulted from a new mutation.


Hemoglobin Gavello - alpha 2 beta 2 47 (CD6) Asp replaced by Gly. A new hemoglobin variant from Polesine (Italy). During a survey for abnormal hemoglobins in Polesine (a region north of the Po river, where beta-thalassemia is very frequent) a slow moving variant was noted in a 79-yr-old woman living in Gavello, a small town in the province of Rovigo. Structural studies demonstrated a previously undescribed amino acid substitution, beta47 Asp replaced by Gly. This new variant has been named Hb Gavello.


Hemoglobin Thailand [alpha 56 (E 5) Lys leads to Thr]: a new abnormal human hemoglobin. A healthy Thai male was found to have an abnormal hemoglobin moving faster than Hb A in starch-gel electrophoresis, in addition to the normal hemoglobin constituents. The abnormal hemoglobin constituted 28% of the whole hemoglobin. The subject was asymptomatic and had normal hematologic findings. Structural characterization revealed that the amino acid substitution was alpha 56 Lys leads to Thr. This variant has never been described previously and it is named Hb Thailand.


An evaluation of the methods for quantitation of hemoglobin A2: results from a survey of 10,663 cases. Microcolumn chromatography and a new test tube method for quantitation of hemoglobin A2 were compared with column chromatography on DEAE-Sephadex, starch block and cellulose acetate electrophoresis to ascertain their relative accuracy, precision, reproducibility and speed. One hundred seventy-four blood specimens, including 90 samples from genetically proven beta-thalassemia heterozygotes were examined. The mean Hb A2 values in normal and beta-thalassemia heterozygotes were: 2.3% and 4.7%, respectively, determined by microcolumn chromatography; 2.3% and 4.9%, respectively, determined by a new test tube method; 2.5 and 4.6%, respectively, determined by column chromatography on DEAE-Sephadex; 2.6% and 4.8%, respectively, determined by starch block electrophoresis; and 2.4% and 4.8%, respectively, determined by cellulose acetate electrophoresis. Although all five methods were found to be reliable and reproducible, the microcolumn chromatographic method and the newly developed test tube method using DE-52 cellulose are the most rapid, reproducible, economical, and well suited for large scale surveys. By microcolumn chromatography, 7,953 school children and 2,710 other cases were screened for the quantity of Hb A2. In these samples, 578 beta-thalassemia heterozygotes were detected.


Differences in affinity of variant beta chains for alpha chains: a possible explanation for the variation in the percentages of beta chain variants in heterozygotes. The alpha and beta chains of the hemoglobins A, S, Leslie and N-Baltimore have been isolated as PMB derivates by CM-cellulose and DEAE-cellulose chromatography. The relative affinities of the betaA, betaS, betaLeslie and betaN-Baltimore chains for alpha chains were measured through quantitation by chromatography of the hemoglobins A and Leslie, A and S, and A and N-Baltimore that were formed when variable amounts of alpha chains were added to a mixture of equal amounts of the appropriate beta chains. The data indicate a greatly decreased affinity of betaLeslie chains for alpha chains; a similar preference of alpha chains for betaA chains was observed for mixtures involving alpha, betaA, and betaS chains, but the affinity of betaS chains for alpha chains was higher than that of betaLeslie chains. The betaN-Baltimore chains assembled with alpha chains at a similar rate as betaA chains. The data as interpreted indicate that the affinity of certain beta chains for alpha chains can be a major post-translational control mechanism which regulates the level of a beta chain variant in heterozygotes.


Fluorescence of Trypan blue in frozen-dried embryos of the rat. Freeze-drying and fluorescence microscopy techniques were combined to create a sensitive method for the visualization of the teratogenic dye, Trypan blue, in both protein-bound and free forms. In the development and initial application of this method, visceral yolk sacs of several gestational ages as well as normal appearing, 12-day embryos obtained from dye-injected rats were utilized. Observations on paraffinized sections of the yolk sac placentae demonstrated that only the protein-bound form of the dye exists in the yolk sac cavity whereas both forms of the dye exist in supranuclear regions of cells of the visceral endoderm. Paraffin sections of the normal appearing, 12-day embryos displayed the protein-bound form of dye within lumina of mid- and hind-gut, and both forms of dye in the primitive mucosa of mid- and hind-gut. The advantages of the method are derived not only from the use of fluorescence microscopy but also from the avoidance of solvents that are employed in more routine microtechniques.


Dehorning the mature goat.

Dehorning the mature goat. Surgical techniques for dehorning the mature goat utilized combinations of sedation and local anesthesia. Numerous factors were considered before surgery was performed. Use of Barne's calf dehorners, tube-type calf dehorners, and elastrator bands are contraindicated in the goat due to the anatomic structure of the frontal sinus. Dehorning female goats late in gestation can induce aboriton; male goats used for breeding should be dehorned well in advance of the breeding season. Owners should be advised that dehorning can be temporatily debilitating to the goat and can alter a goat's social status within a herd.


Passive transfer of colostral immunoglobulins from ewe to lamb and its influence on neonatal lamb mortality. The transfer of immunoglobulin G (IgG) and immunoglobulin M (IgM) from ewe to lamb was quantitated to determine the occurrence of failure in passive transfer. Concentrations of IgG and IgM in ewe serum did not correlate with those in the colostrum. Colostrum from all ewes contained abundant amounts of immunoglobulins when compared with serum values, with IgG being selectively concentrated over IgM. Absorption through the intestinal tract of the lamb appeared to be a nonselective process, lacking predilection for IgG and IgM. All lambs tested 24 hours after birth absorbed colostral immunoglobulins to some extent; however, 13 (14%) of 91 clinically normal lambs demonstrated some failure of passive transfer. In contrast, failure of passive transfer was found in 27 (46%) of 59 lambs dying of natural causes between 24 hours and 5 weeks of age. Evidence presented emphasizes the importance of absorption of adequate amounts of immunoglobulins to enable the newborn lamb to survive the first few weeks of life.


Survey of Toxoplasma antibodies among sheep in western United States. A survey was conducted to determine the prevalence of toxoplasma antibodies among breeding ewes and among lambs slaughtered for food in western United States. Each serum was tested by the indirect hemaglutination method, using microtiter technique. Agglutination (greater than or equal to 2 +) at the 1:64 dilution was considered to be a positive reaction. Of 2,164 ewes from 18 flocks tested in California, 523 (24%) were seropositive for Toxoplasma gondii, with prevalence rates among flocks ranging from 4 to 51%. In 9 of those flocks, 1,495 ewes were stratified by whether ewes had lambed or were barren. On an overall basis, the antibody prevalence was similar (about 25%) in both groups, but there was a significant difference (P less than 0.05) in 1 flock in which 30% of the nursing ewes were seropositive, compared with 21% of the barren ewes. Of 1,056 market lambs from 19 lots tested, 85 (8%) were seropositive. The antibody prevalence in lambs tested at slaughter in California, by state of origin, were: Oregon, 11/51 (22%); Nevada, 32/159 (20%); Idaho, 12/147 (5%), and California, 30/699 (4%).


Effects of thin ewe syndrome on reproductive efficiency. A debilitating condition affecting mature ewes was found to be associated with the visceral form of caseous lymphadenitis, chronic progressive pneumonia, and Corynebacterium pyogenes infections. The condition was termed thin ewe syndrome. Affected and normal ewes were compared for reproductive efficiency by breed and age; differences in reproductive efficiency between affected and normal Rambouillet and Columbia ewes were highly significant (P less than 0.01). Although not statistically significant, the trend in Targh ee ewes was similar. There was a direct correlation between occurence of the syndrome and increasing age for all breeds.


Facial and visceral arch development in the mouse embryo: a study by scanning electron microscopy. The morphogenesis of the face and visceral arch region were studied by scanning electron microscopy in 63 mouse embryos between 8 and 13 days post coitum. The developmental stages were determined by reference to Theiler's (1971) scheme for the categorization of the normal stages of development. After the cervical fold is formed (stage 12) the mandibular primordium appears (stage 13) followed by the primordia of arches II and III (stage 14 with arch IV forming last (stage 15). Arches II, III and IV regress in reverse order, with no evidence that a cervical sinus pouch is formed. Placodes of the sensory ganglia from cranial nerves 7, 9 and 10 are formed in the first, second and third visceral grooves respectively. Formation of the external auditory meatus and its surrounding tubercles were also observed. Morphogenesis of the upper face is dominated by the midsagittal grove, which extends into the stomatodeum; and by the medial nasal, lateral nasal and maxillary processes. The temporal changes in shape and the interrelationships of the structures mentioned are described in detail.


The relationship between sarcomere length in the soleus and tibialis anterior and the articular angle of the tibia-calcaneum in cats during growth. Sarcomere number and sarcomere length were studied in six groups of kittens ranging in age from 10 minutes to 5 months and compared with those of adult cats. Although the soleus muscle is a slow contracting muscle and the tibialis anterior a fast contracting muscle, both have previously been shown to have the same range relative to ankle movement. For a given angle of articulation the sarcomere length was found to be the same at all ages except perhaps for the newly born. In contrast, the sarcomere number differed considerably, being much higher in the older animals. The relationship between active tension and muscle length was also measured, and again no difference was found between the muscles at any age, although the shape of the curves for the soleus and tibialis anterior was different.


The penile bone and anterior process of the rat in scanning electron microscopy. The penile bone and anterior process were made anorganic for scanning electron microscopy. The mature bone has a basal bulb and a long, cylindrical shaft bevelled at its tip to fit under a matching surface on the anterior process, giving rise to a bevelled 'suture'. A rough, resting, Sharpey-fibre bone surface covers the base and tip of the bone, the dorsal crest along the shaft, and parts of the lateral and ventral surfaces. The penile bone grows by endochondrial ossification at its basal end, but the cartilage cells are randomly disposed and not arranged in columns as in most 'long' bones. The growing bone, at 8 weeks, shows evidence of resorption externally where the base 'waists in' to the shaft: the corresponding endosteal surface within the basal bulb is formative, in accordance with the 'V-principle' of remodelling. It is concluded that the anterior process, penile bone and proximal erectile body (corpus cavernosum) form a firm, tightly fastened, articulating chain, perhaps serving to aid penetration.


The anterior and the posterior longitudinal ligaments of the lower cervical spine. The anterior and the posterior longitudinal ligaments (ALL and PLL) of the cervical spine were examined. The ALL and the deep layer of the PLL are continuous, and surround the vertebral body. The superficisl layer of the PLL surrounds the dura mater, nerve roots and the vertebral artery, suggesting that this membrane may serve as a protective membrane for the soft tissues inside the vertebral canal rather than as a conventional ligament.


Light and electron microscopic studies on the intrinsic innervation of the guinea-pig seminal vesicle following selective axotomy. Selected peripheral autonomic nerves have been surgically divided or removed and the seminal vesicles subsequently examined using neurohistochemical and electron microscopic techniques. Following bilateral hypogastric anf pelvic nerve transection, the arrangement and distribution of intramural axons 14 days after operation were similar to those in control specimens. In contrast, removal of the pelvic plexus was accompanied by a gradual reduction of catecholamine and acetylcholinesterase so that by the seventh post-operative day nerves were not observed light microscopically in the muscle coat or the submucosa. These observations have been endorsed using electron microscopy, and the fine structure of intramural autonomic nerves in response to axotomy has been monitored during the post-operative period. It has been concluded that the cell bodies of axons which supply the wall of the seminal vesicles are located within the pelvic plexus and do not extend proximal to the sites of division of the hypogastric and pelvic nerves.


Ultrastructural localization of adrenergic nerve terminals in the circular muscle layer and muscularis mucosae of the rat duodenum after acute treatment with 6-hydroxydopamine. The ultrastructure of the intrinsic adrenergic innervation of the circular muscle coat and muscularis mucosae of rat duodenum has been studied following acute treatment with 6-hydroxydopamine. Adrenergic terminals were found among intramuscular nerve bundles. They were most numerous in the outer layer of the circular coat, where close neuromuscular contacts were commonly encountered. Adrenergic terminals also innervated the inner layer of the circular coat and the muscularis mucosae, where only wide neuromuscular contacts have been found. The evidence suggests that smooth muscle cells in the rat duodenum may be directly influenced by adrenergic nerves.


Development of ossification centres in the squamous portion of the occipital bone in man. The development of ossification centres in the squamous portion of the human occipital bone is described on the basis of anomalies observed in a large series of skulls. The interparietal part develops from three pairs of centres in membrane--one pair for the lateral plates, one pair for the central piece, and the third pair representing the pre-interparietals. The supraoccipital part develops from five centres in cartilage--two centres for each lateral segment and a single centre for the central segment. The supraoccipital part extends from the posterior margin of the posterior condylar fossae to about 2 cm above the external occipital protuberance and about 0.4 cm above the superior nuchal line near the lambdoid suture.


Pattern of talar articular facets in Indian calcanei. The variations in the talar articular facets on 401 normal Indian calcanei have been observed and classified. Type 1 calcanei have one continuous facet on the sustentaculum tali extending on the antero-medial corner of the distal part of the calcaneus (268 cases--67%). Type 2 calcanei have two articular facets, one on the sustentaculum tali, and another on the distal part of the calcaneus (104 cases--26%). Type 3 calcanei have a single well defined facet on the sustentaculum tali (21 cases--5%). Type 4 calcanei have a single facet on the sustenaculum tali extending on to the antero-medial corner of the distal part of the calcaneus, but this facet is continuous with the posterior talar facet of the calcaneus (8 cases--2%).


Proliferation and differentiation of trophoblast in the establishment of the rat chorio-allantoic placenta. The morphological differentiation of the elements contributing to the chorioallantoic placenta of the rat was studied between days 6 and 16 of gestation, and DNA synthetic activity was investigated in animals killed 1 hour after injection of tritiated thymidine. The chorionic lamina is formed from the epithelial cells lining the ectoplacental cavity, though it is possible that a contribution is made by ectoplacental cone cells at the mesometrial pole of the cavity. From day 8 onwards a high proportion of cells was labelled in both cone and lamina, with the labeliing index reaching a peak of about 80% at 10-11 days. There was no corresponding peak in mitotic activity, which remained at a high level in all regions up to day 12. The amount of thymidine incorporation, as judged by grain count per nucleus, varied. At 9 days a significantly higher grain count was obtained in a central core of cells in the ectoplacental cone, and at day 10 the grain density of labelling in the cone was very much heavier than in the lamina. This difference in labelling intensity was maintained until day 12, and there was no evidence of any influx of heavily labelled cells from the cone into the developing labyrinth.


Observations on the intracranial carotid rete and the hypophysis in the mature female pig and sheep. It is accepted that in the pig the intracranial carotid retia are connected across the midline by numerous arteries lying within the intercavernous sinus. The present study has demonstrated that these vascular elements fill the greater part of the very deep sella turcica, the cranial hypophysis occupying an almost suprasellar position. In the sheep the anastomosis between the carotid retia is limited to a few arteries crossing the midline posterior to the hypophysis, and the gland lies wholly within the sella turcica. It is suggested that the position of the cranial hypophysis in the mature female pig results from the inward and upward pressures exerted on the hypophysis by the carotid retia and their extensive interconnexions in this species.


The ultrastructure of the sensory nerve endings in the articular capsule of the knee joint of the domestic cat (Ruffini corpuscles and Pacinian corpuscles). Two types of mechanoreceptor have been found in the articular capsule of the  knee joint of the domestic cat--Ruffini corpuscles and Pacinian corpuscles. Ruffini corpuscles are situated in the stratum fibrosum and consist of 2 to 6 cylinders. Each cylinder is made up of an afferent axon (diameter 3-4 micrometer), its swellings and terminal processes, Schwann cells enveloping the nerve swellings and terminal processes, endoneural connective tissue and a perineural capsule. The perineural capsule is incomplete in Ruffini corpuscles. The Pacinian corpuscles are 20 to 40 micrometer wide and 150-250 micrometer long. They are situated in groups of up to five at the boundary between the stratum synoviale and the stratum fibrosum. The afferent axon is myelinated (diameter 3-5 micrometer). Its terminal portion is inside the inner bulb which is formed of modified Schwann cells. Each corpuscle is enveloped by a perineural capsule (4-8 layers). The ultrastructure of the Pacinian corpuscles is compared with the ultrastructure of the skin receptors in the cat.


The mitotic response of the stratified squamous epithelium at the edge of large perforations of the tympanic membrane in guinea-pigs. Large perforations of the tympanic membrane were made in groups of guinea-pigs. The mitotic response in the stratified squamous epithelium at the edge of the wound was examined in perforations between 1 and 28 days after injury. Peaks of activity were discovered at 2, 15-16 and 24 days after wounding. It was also found that the maximal proliferative response was not at the immediate wound edge, as is usually maintained, but as some 2 mm from the wound edge. The results correspond remarkably well with work previously done by the present author on wounded rectal mucous membrane. The results are examined in the light of the chalone hypothesis of mitotic control.


Ultrastructural studies on the differentiation of spermatids in the domestic fowl. Four phases of spermatid maturation are recognized on the basis of nuclear morphology. The formation of the acrosome, perforatorium and axial filament complex are described in relation to these phases. The functional significance of the microtubular systems in nuclear elongation and spermatid curvature are discussed. A membranous structure, hitherto unidentified, and referred to in this study as the 'membrane body' is compared with the chromatoid body. Morphological evidence suggests that this structure, together with the annulate lamellae, removes excessive nuclear material.


Insulin deficiency and cell proliferation in oral mucosal epithelium of the rat. The duration of the cell cycle (C) and its component phases (G1, S, G2 and M), the rate of cell proliferation, and the renewal time, in the epithelium of the hard palate of alloxan-diabetic rats have been determined and compared with values of the same variables obtained previously from normal rats. The data have been derived by means of autoradiography with [3H]thymidine and the method of labelled mitoses. The values for the normal animals were found to be: G1 = 38 hours, S = 8 hours, G2 = 1 hour, M = 1 hour, C = 48 hours (or 2.1%/hour); and for the diabetic animals were: G1 = 42.5 hours, S = 8.5 hours, G2 = 1 hour, M = 1 hour, C = 53 hours (or 1.9%/hour); and for the renewal time for the epithelium, 6.5-8 days. In the diabetic animals the duration of S was increased by 6%, G1 by 12% and the cell cycle by about 10%. The reduced rate of cell proliferation that is associated with insulin deficiency may contribute to the slower rate of wound healing in subjects with diabetes mellitus.


Postnatal growth of Brunner's glands in the mouse. In the newborn mouse the glands of Brunner consist of a few tubular downgrowths from the proximal duodenal crypts. Within three weeks the characteristic 'comma' shape of the gland is established by later downgrowths from more distal growths. The gland cells, although specialized from birth, show a high mitotic index, and a high labelling index with 3H-T, during the first three weeks, and particularly during the first two weeks. Nevertheless, the daily mitotic rate during this period is insufficient to account for the daily addition of glandular cells, suggesting that there is a continuing contribution of cells from the crypts. After this time, however, the mitotic activity of the mature gland cells is sufficient to account for the continuing increase in cell population. After the fourth postnatal week the mitotic and labelling indices decline markedly, and although mitoses are rarely seen in individual sections from older animals, cellular addition at a very slow rate is sufficient to account for the gradual expansion in size of the gland, and the process continues long after the adult body weight has been established.


The course and relations of the left phrenic nerve in the neck. In the neck, the left phrenic nerve is in a position that corresponds exactly to that of the right phrenic nerve. Both cross and second part of the subclavian arteries. On the left side there is an additional relationship of the nerve to the subclavian artery in the thorax, where it descends in front of the first part of the artery.


National Health Service laboratories in England, 1966-74. Laboratory workloads increased substantially between 1966 and 1974, the total number of laboratories was reduced, and productivity improved. The trends are likely to continue, but in the present economic situation the availability of accommodation will be an important constraint in determining the pattern of future development.


The Birmingham Histopathology Data Pool: a co-operative project among 10 laboratories. In 1970 the Birmingham Histopathology Data Pool was established to collect information on biopsies of surgical specimens from three hospitals. The scheme has gradually expanded and 10 hospitals now participate.  The pathologist gives each specimen a numerical code based on the Systematised Nomenclature of Pathology (SNOP). The information is processed by computer and stored on cumulative magnetic tape file. At regular intervals (at three, six, and nine months) 'printouts' listing all the information recorded within the interval are produced and a cumulative print-out is issued when the information for a whole year is complete. The data pool system has provided accurate alphabetical and SNOP diagnostic files and has simplified retrieval of data for both follow-up and research purposes. The pathologist may use the computer to retrieve and analyse information from the data pool for this own use or on behalf of clinicians, but he may use information from laboratories other than his own for research purposes and publication only with the permission of the pathologists who submitted the data.


An on-line computer system for histopathology reporting. An on-line computer system was developed for issuing histopathology reports as part of an integrated hospital information system. Input is through a Cossor visual display unit with a typewriter keyboard to a Univac 418 III computer. Stored information is available to authorised hospital staff via similar visual display units located in the wards and laboratories. Existing programs and computer staff were used to provide the new service. It has resulted in better method, speedier communication, and saving of laboratory staff time. The system has yet to be fully tested but initial reactions are favourable and indicate that the investment in computer staff time and extra laboratory equipment will be cost effective.