The cellular immunity in patients sensitized to Candida albicans and its corresponding humoral response.

Ten non-sensitized normal blood donors and thirty five patients with a strongly positive intracutaneous test to Candida albicans, positive anamnesis to Candida allergy, or with an actual Candida infection demonstrated by positive cultures of the focus, were studied. In all of them, an evaluation of the humoral and cellular response to Candida antigens, was performed both in vivo and in vitro. The results obtained in the tests performed in the control group were considered as extreme values of a normal response and taken as reference in order to evaluate the patients' response. The results of the test performed on the 35 patients were processed in an IBM S.370/M.125 computer and submitted to a General Taxonomy Program in order to group the patients according to their characteristics and similar behaviour. Two main groups, each one including three minor groups, were obtained and only one individual was not classified. According to this classification it was possible to distinguish two immunological patterns: a) The patients that had a normal or increased percentage of T lymphocytes were capable of responding adequately to Candida albicans antigens. They showed positive immediate and delayed skin tests, increased hemagglutination titres, increased lgE values, and their lymphocytes were capable of undergoing positive blast transformation. Those patients from this group who had a candidaemia at the time of the study, reached the highest hemagglutination values and presented precipitin antibodies as a characteristic. b) The patients that had a decreased percentage of T lymphocytes presented a partial deficiency in their response to Candida albicans antigens. They showed negative delayed skin tests; hemagglutination and precipitation tests both negative, normal lgE values and their lymphocytes did not undergo blast transformation. These findings suggest that a normal percentage of T cells is required in order to obtain a suitable cellular response against Candida albicans, and that an appropriate co-operation between T and B cells is also necessary in order to obtain a good humoral response to Candida antigens.


A note on the distribution of the number of exclusions to be expected in paternity testing.

The distribution of the number of exclusions to be expected in paternity testing is derived, and the calculation of the mean and variance of this distribution is indicated.


Chronic neutropenia in childhood. Analysis of 16 cases and a review of the literature.

We analyzed the clinical histories and hematologic information concerning 16 persons in whom chronic neutropenia was discovered early in life. Only two of them, those with the lowest mean neutrophil counts, had frequent and severe pyogenic infections. Almost all the infections were caused by Staphylococcus aureus or by enteric microorganisms and involved the skin, respiratory tract or gastrointestinal system. The prognosis in our subjects or in patients described in the literature could not be predicted from the bone marrow morphology, presence or absence of blood monocytosis, pattern of genetic transmission or results of special tests of neutrophil function. We propose that the complex nomenclature associated with chronic neutropenic states be discarded until a better basis for classification becomes available.


Are agents affecting platelet functions clinically useful?

Notwithstanding the large number of clinical trials, most of them designed and performed according to the requirements of modern clinical pharmacology, only a few firm clinical recommendations on drugs affecting platelet function in the prevention of arterial or venous thrombosis can be made at present. There is no good evidence for the clinical effectiveness of aspirin or any other drug affecting platelet function in patients with peripheral arterial occlusion or after vascular grafting. In cerebrovascular disease there is reasonable evidence that the administration of sulfinpyrazone can significantly reduce cerebral ischemia or mortality, but similar trials performed with aspirin, dipyridamole or clofibrate failed to reveal a significant difference in favor of the experimental treatment. Patients with angina only were shown to benefit from treatment with clofibrate, but prospective trials with dipyridamole or aspirin in the primary or secondary prevention of myocardial infarction did not reveal a significant reduction in morbidity or mortality in the experimental group. Use of a combination of the latter two drugs did, however, reveal a reduction in morbidity and mortality. In patients with prosthetic heart valves, there is firm evidence that dipyridamole and sulfinpyrazone therapy can normalize decreased platelet survival, an effect which has been shown to correlate well with the incidence of thromboembolism. Provided further trials lead to confirmatory conclusions, drugs inhibiting platelet function associated or not with oral anticoagulants may constitute an ideal prophylaxis in patients with a substitute valve. There is still much uncertainty as to whether dipyridamole, given in addition to conventional treatment, benefits patients with membranous or mesangiocapillary glomerulonephritis. The same holds for drugs inhibiting platelet function after kidney or heart transplantation in man. Only scanty reports are available on the usefulness of drugs affecting platelet function in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Three different types of antiplatelet drugs are available for the prevention of postoperative deep vein thrombosis: dextran, oral drugs also affecting platelet function and heparin administered subcutaneously in small doses. In orthopedic surgery dextran 70 administered before and every second day after surgery was the drug showing the most convincing reduction in the incidence of phlebographically proved deep vein thrombosis. Major orthopedic surgery is precisely the type of surgery in which the effectiveness of small dose heparin is much in doubt and in which the effectiveness of aspirin and dipyridamole is still to be confirmed. In general surgery, use of a combination of 1 g aspirin and 0.225 g dipyridamole daily was shown to offer approximately the same level of protection as small doses of heparin, land these two forms of prevention seem to offer a greater degree of protection than dextran...


Extrinsic allergic alveolitis after Aspergillus fumigatus inhalation. Evidence of a type IV immunologic pathogenesis.

Three weeks after a massive inhalation of mold present on infected oats, a farmer's wife had extrinsic allergic alveolitis. Aspergillus fumigatus was cultured from the moldy oats and from deep bronchial washings obtained at fiberoptic bronchoscopy. Spores and hyphae characteristic of Aspergillus species were demonstrated within granulomas in the pulmonary tissue obtained by transbrochial biopsy. Serum precipitins, delayed (48 hour) cutaneous hypersensitivity and in vitro lymphocyte transformation to A. fumigatus were demonstrated. The findings in this case suggest that a type IV immunologic response and subsequent (lymphocyte-mediated) tissue inflammation may underlie the pathogenesis of this and other forms of hypersensitivity pneumonitis.


Monoclonal IgE with renal failure.

Only four cases of immunoglobulin E (IgE) monoclonal "gammapathies" have been reported previously. Discussed here is a 57 year old man who presented with hypertension and the nephrotic syndrome. A monoclonal IgE-kappa component (0.6 mg/ml), which did not appear as an M spike on protein electrophoresis, was demonstrated by immunoelectrophoresis in the serum and urine. The patient's condition deteriorated rapidly due to renal failure, and he died five weeks after the diagnosis was made. Pathologic examination disclosed extensive glomerular lesions, but amyloid was not detected by light or electron microscopy. The possible relationship between the monoclonal gammapathy and kidney impairment is discussed.


Decentralization in the New York City Department of Health: reorganization of a public health agency.

Since the World War I era there has existed within the New York City Department of Health a basic internal struggle between staff directing the bureaus at the central office and the district health officers operating field health centers throughout the city. Recently, in a five-year period, there was a dramatic reorganization of the Department which markedly affected its orientation and programs. In 1972 a new Commissioner initiated a reorganization of the Department which succeeded in decentralizing field operations in contrast to earlier efforts which had failed to reach this objective. The roles of bureaus and districts were redefined, with the latter receiving budgetary authority, authority to supervise personnel, assignment of health managers, and the implementation of a district cost accounting system. While operational decentralization has occurred, policy setting and resource allocation in response to local needs remain central functions.


Evaluation of two phenanthrenemethanols for antimalarial activity in man: WR 122,455 and WR 171,669.

Two phenanthrenemethanols, WR 122,455 and WR 171,669, were tested in man for oral tolerance, toxicity, and efficacy against Plasmodium falciparum. In healthy subjects, gastrointestinal symptoms limited single-day dosage of WR 122,455 to 800 mg and WR 171,669 to 1,260 mg. No laboratory abnormalities phototoxicity, or gastrointestinal blood loss were noted in the subjects receiving these drugs. In subjects infected with malaria, WR 122,455 cleared parasitemia when given for 1 day in doses from 440 to 880 mg; recrudescences occurred in these subjects who were infected with either chloroquine-sensitive or chloroquine-resistant P. falciparum. However, WR 122,455 at 480 mg/day for 3 to 6 days cured 9/9 cases of chloroquine-resistant and 4/4 cases of chloroquine-sensitive P. falciparum infection. WR 171,669 at 1 g/day for 3 days cured 6/6 subjects with chloroquine-resistant and 3/3 cases of chloroquine-sensitive infection. Both agents cleared parasitemia and fever promptly.


An evaluation of malaria fluorescent antibody patterns in several remote island populations of the New Hebrides, Solomons, Western Carolines, and New Guinea.

From a representative sampling of several remote populations living on the Banks and Torres Islands (New Hebrides), the Eastern and Southern Districts of the Solomon Islands, the Western Caroline Islands (U.S. Pacific Trust Territory), West New Guinea (Indonesia), and Papua New Guinea, 752 sera were examined for fluorescent antibodies to the four species of human malaria, and the results were compared to already published parasite survey data based on blood smears and medical examinations. Antibody prevalence data confirmed the presence of significant endemic malaria among most of the visited islands in the New Hebrides, and a variable but smaller amount of malaria in the Solomons. On those islands known to be free of malarial vectors, data were compatible with importation of self-limited infection by travelling residents. Malarial infection occurred in from 40% to 100% of the New Guinea villages that were visited, and was entirely absent from the Western Caroline Islands. The actual proportions of malarial species in endemic areas were not accurately reflected by relative antibody titer levels to the different species, possibly due to unpredictably high heterologous antibody reacitons following multiple mixed infections.


Enzyme- and 125I-labeled anti-immunoglobulin assays in the immunodiagnosis of schistosomiasis.

An enzyme-linked immunosorbent assay (ELISA), and radioimmunoassays using antigen bound to plastic tubes or microcrystalline particles, were adapted for the indirect serological measurement of anti-schistosome antibodies. These alkaline phosphatase and 125I-labeled anti-immunoglobulin techniques were found to be highly quantitative and adaptable. Comparison showed them to be considerably more sensitive than the indirect hemagglutination and indirect fluorescent antibody techniques. Using adult S. mansoni freeze-thaw antigen, anti-schistosome antibodies were detected in sera from patients infected with Schistosoma mansoni and S. haematobium. However, results in patients with schistosomiasis haematobium were generally intermediate between those of patients with schistosomiasis mansoni and normal, uninfected controls.


Dapsone chemotherapy of Mycobacterium leprae infection of the neonatally thymectomized Lewis rat.

In order to learn whether the neonatally thymectomized Lewis rat (NTLR) infected with Mycobacterium leprae could serve as a model for chemotherapeutic studies in a situation resembling that found in human lepromatous leprosy, NTLR inoculated with M. leprae either locally or intravenously 9 to 16 months earlier were treated for from 1.5 to 8.5 months with dapsone (4,4'-diaminodiphenylsulfone, DDS) incorporated in the rat chow in the concentration providing the minimal inhibitory concentration of the drug for M. leprae and in the 100-fold larger concentration. NTLR were killed at intervals; the M. leprae were counted and passed to mice. Treatment with the smaller dosage of dapsone neither killed M. leprae nor reduced the number of organisms in the bacterial populations, whereas treatment with the larger dosage both killed M. leprae and reduced their numbers. The rate at which the organisms were killed (i.e., rendered noninfective for mice) was much the same as that in patients treated with dapsone in comparable dosage. The dead organisms were removed from the rat tissues at a faster rate than encountered in patients. The NTLR may indeed be suitable for chemotherapeutic studies relevant to man. In addition, the more rapid disappearance of dead M. leprae from the rat tissues may facilitate the study of treatment regimens designed to eradicate persisting viable organisms.


Actin-like filaments in the Sertoli cell junctional specializations in the swine and mouse testis.

Microfilaments at the junctional specializations between adjacent Sertoli cells and between the Sertoli cell and the late spermatid of the mouse and swine testes bind HMM and form arrowhead complexes with a periodicity of about 35 nm. The arrowhead formation is inhibited when the tissues are treated with HMM in the presence of ATP. These observations show that the microfilaments are actin-like in nature. The functional significance of these filaments in the Sertoli cell is discussed.


[Non-Hodgkin hematosarcomas. Classification of the Reference Center of the World Health Organization (WHO)].

At the request of the Leukaemia and Haematosarcoma Reference Centre of the World Health Organisation (W.H.O.), one of the authors (G.M.) has suggested a classification taking into account the most recent knowledge and all parameters (histological, cytological and immunological) necessary for the categorisation of non-Hodgkin's haematosarcomas. He has employed traditional terminology, thereby avoiding the jargon used by certain authors which is not justified in the light of modern scientific knowledge which, more than ever, merits the use of classical terminology. The authors present this W.H.O. classification for the first time to the french press. The reader will find familiar terms such as "lymphosarcoma", which may take a nodular or diffuse form (in the second case the recently identified immunoblastic form is introduced and mycosis fungoides is placed in the category) and reticulosarcoma. Microscopic typing of a haematosarcoma is essential since the various types differe considerably in their sensitivity to treatment with a corresponding difference in the chance of cure. The potential for cure is also dependent upon the topographic stage which should be determined by a series of routine step which may still be recommended today but which may be useless in the future by virtue of the frequency of disseminated forms in relation to localized forms, and of the remarkable effectiveness and constant progress of chemotherapy and immunotherapy.


[Comments on the WHO Reference Center classification of non-Hodgkin hematosarcomas].

The authors discuss the W.H.O. classification of neoplastic disorders of lymphatic and haematopoietic tissue proposed by G. Mathé and H. Rappaport. They note the points in common with previously published new classifications and make a number of remarks and criticisms. They stress the point most open to discussion: maintenance of the concept of reticulosarcoma. They propose the parallel use of several classifications, including the old nomenclature of Rappaport, in routine histopathology during the comming years.


Lymphocyte subpopulations in the peripheral blood of patients with farmer's lung.

The numbers of mononuclear cells having receptors for sheep red blood cells (T lymphocytes) or complement (B lymphocytes) in the peripheral blood of farmer's lung patients were determined. In patients recovering from a clinical episode of farmer's lung or exposed to moldy hay or fodder, both the percentage of T lymphocytes and the T lymphocytes per mm3 were reduced, whereas the number of B lymphocytes remained within normal limits. Farmer's lung patients having no exposure to moldy hay or fodder had T and B lymphocyte numbers similar to a normal population.


Characterization of immunocompetent cells recovered from the respiratory tract and tracheobronchial lymph node of normal guinea pigs.

To gain insight into the structure of the lung's immune system, the identity and function of immunocompetent cells in the broncho-alveolar air spaces and tracheobronchial lymph nodes of normal guinea pigs were examined. Guinea pig thymus-derived (T) lymphocytes (mediators of cellular immunity) were identified by their ability to form rosettes with rabbit erythrocytes (E rosettes). Bone marrow-derived (B) lymphocytes (mediators of humoral immunity) were identified by their ability to form rosettes with sheep erythrocytes sensitized with antibody and complement (EAC rosettes) and by the presence of surface immunoglobulin, detected by direct immunofluorescence. Total lung lavage yielded 14+/-5.0 X 10(6) (mean +/- SD) cells. There were 68+/-5 per cent cells of the monocyte-macrophage series as judged by morphology, the ingestion of latex particles, and the uptake of neutral red; 20+/-9 per cent were eosinophils, and 12+/-5 per cent were lymphocytes. Stable populations of T and B lymphocytes were recovered from guinea pig airways and tracheobronchial lymph nodes. T cells represented 76 per cent of lymphocytes from the airways and 64 per cent of lymphocytes in tracheobronchial lymph node; B cells equalled 14 per cent and 30 per cent, respectively. The functional potential of T cells present in the lung and tracheobronchial lymph node was demonstrated by their proliferative response to phytohemagglutinin. These results indicated that, although macrophages are the predominant cell type, viable T and B lymphocytes are present in the guinea pig broncho-alveolar air space. The composition of these cells is comparable to what has been observed in normal human lungs and provides preliminary evidence that the guinea pig may be a useful model for humans. This report also describes a method using 2 vital stains whereby macrophages, lymphocytes, and rosetted lymphocytes can be distinguished in unseparated cell suspensions prepared from bronchial aspirates.


Tissue adhesive vs sutures in closure of incision wounds. A comparative study in human skin.

Two different standard incisions were used to compare the healing of wounds closed with normal "atraumatic" surgical technique and with a tissue adhesive. Healing was recorded by serial photography. It was found that wounds, which were not under tension postoperatively, the resulting scar was cosmetically better when tissue adhesive was used compared with conventional methods of suture.


Late complications of scalding in children: treatment and prevention.

Children between the ages 1 to 3 years are particularly prone to burns by their constant desire to pull down containers of hot fluids. The resulting burns produce serious complications such as hypertrophic scars and scar contractures, which can be severe enough to cause growth disturbances. A series of 31 cases of these accidents resulting in the above sequelae was investigated. These complications are however the end result of a chain of unfortunate events any or all of which could have been avoided. Usually the scald could have been prevented by greater vigilance on the part of the parents. Once late complications have developed, excision of the scar tissue and subsequent skin grafting or other reconstructive procedure should be performed. However, in spite of satisfactory results, these complications have a tendency to recur during the growth period.


Repair of skin and soft tissue loss of the lower leg with cross-leg flaps.

Forty patients with severe leg injuries associated with skin or soft tissue loss were treated. Cross-leg flaps were used. The flaps healed well. Special attention was paid to the pre- and postoperative periods of disability of the patients. The former were very long (37.7 months) compared to the latter (10.5 months) which ceased when the patient became fit for work.


Modification of Krukenberg's kineplastic operation.

Little attention has been paid lately to the kineplastic operations of amputation stumps. But Krukenberg's procedure, the forcipisation of forearm amputation stumps introduced in 1917 has, nevertheless survived. The authors have modified the operation. The skin of the forearm is split with a U-shaped incision. All muscles are saved. The interdigital commissure is covered with two triangular flaps. The remaining skin defect is left on the dorsum of the radial branch and covered with a free split skin graft. The skin graft is not used to cover the contact surface. In the Orthopaedic Hospital of the Invalid Foundation of Helsinki nine hands of seven patients have been operated during the years 1969--73 using this method.


A rhomboid nose-side flap in nasal skin defects.

A reliable flap method for covering a defect caused by the excision of basal cell carcinoma of the alar region is presented. It is suitable for an out-patient procedure. The flap is elevated from the side of the nose. The design of the flap is as follows: its caudal margin coincides with the cephalad margin of the lesion; the medial side of the flap is drawn parallel to the dorsum of the nose; the cephalad side runs back at an acute angle to the lower lid below the eye, incorporating a part of the lower lid and cheek tissue in the flap. Twenty basal cell carcinomas have been treated at the Department of Dermatology, Helsinki University Central Hospital between 1973--1975 using the flap with good cosmetic results. This flap is a useful alternative to the naso-labial flap in a Finnish nose.


Ulcerating paraffinoma.

One case of an ulcerating paraffinoma of the male mammary gland and another of the penis are reported. The former is the third and the latter the eighth of its kind described in the literature. Psychopathological features were associated with both cases, and additionally impotence with the latter. The treatment of paraffinomas is surgical. Subcutaneous mastectomy was performed on the mammary gland, leaving a high proportion of the affected skin in situ. Recovery was slow and the cosmetic end result not satisfactory. Re-injection of paraffin later required total excision of the entire anterior thoracic skin and subcutaneous tissues and skin grafting. The penile paraffinoma was treated by complete excision and again subsequent skin grafting. Both the functional and cosmetic results of the latter were good.


Double-blind titrated-dose comparison of metoprolol and propranolol in the treatment of angina pectoris.

The effectiveness of metoprolol in relieving angina pectoris was compared with that of propranolol at equipotent dosages in a series of 20 patients. Before double-blind periods propranolol was given in gradually increased dosages to obtain a maximal effect for each individual patient. The responses were monitored using subjective assessment based on attack rate and nitroglycerin consumption, as well as objective maximal exercise testing. Both compounds significantly increased the exercise tolerance on a bicycle ergometer, and relieved angina as assessed subjectively. No significant differences were found between the responses to metoprolol and propranolol. The mean increase in exercise tolerance amounted to 36% with metoprolol. Biochemical monitoring revealed no harmful effects. Two cases of rebound phenomenon were observed at the transition from metoprolol to placebo. It was concluded that metoprolol is a useful new cardio-selective beta-blocking compound equipotent to propranolol in the treatment of angina pectoris.


Control of thyrotoxicosis with sotalol.

Sotalol, a beta-adrenergic blocking agent devoid of intrinsic sympathicomimetic activity and local anaesthetic properties, was assessed in a double-blind cross-over study for the symptomatic treatment of 10 patients with thyrotoxicosis. The heart rate and clinical thyrotoxicosis index were significantly lower than with the placebo or with no treatment. The values of free thyroxine and triiodothyronine in the serum did not change. Because of its pure beta-adrenergic blocking effect, sotalol is suitable for the symptomatic treatment of thyrotoxicosis.


R plasmids in Streptococcus agalactiae (group B).

Two plasmids determining resistance to tetracycline (RIP500) and to chloramphenicol, erythromycin, lincomycin, and pristinamycin I (RIP501) were isolated from a strain of Streptococcus agalactiae. The frequency-of-resistance loss is very low for RIP500 (<3 x 10(4)) but higher for RIP501 (the efficiency was dependent upon the curing agents and incubation temperature and varied between 0.5 and 96%). Derivatives susceptible to all drugs were also obtained. RIP500 and RIP501 have similar molecular weights (17.9 x 10(6) and 20 x 10(6), respectively) and represent different percentages of total deoxyribonucleic acid (0.4 and 4%, respectively). The number of copies of RIP500 and RIP501 per cell is different, and these plasmids are likely replicated under different kinds of control (stringent and/or relaxed). No plasmid deoxyribonucleic acid was found in a derivative of strain B96 susceptible to all drugs.


[Combination of bacteriostatic and bactericidal drugs: lack of significant in vitro antagonism between penicillin, cephalothin, and rolitetracycline].

Although it is generally believed that bactericidal and bacteriostatic drugs should not be combined in vivo, in vitro experiments using the checkerboard dilution technique revealed no antagonism between penicillin/cephalothin and rolitetracycline but rather additive or synergistic activity of either drug combination in 40 to 50% of 20 Escherichia coli, and 14 Staphylococcus aureus strains. Slight antagonism occurred only between 3 and 8 h after combining penicillin/cephalothin and rolitetracycline in either bacteriostatic or bactericidal concentrations, but not after 24 h of incubation, nor was antagonism found with combinations of these drugs in bacteriostatic concentrations. Neither bacteriostatic nor bactericidal activity of penicillin/cephalothin and rolitetracycline was inhibited by pretreatment of one E. coli strain with bacteriostatic rolitetracycline or bacteriostatic penicillin/cephalothin concentrations. Penicillin and cephalothin could exert a bactericidal effect after 2-h exposure of the E. coli strain to bacteriostatic rolitetracycline concentrations. Combined action of subinhibitory penicillin and rolitetracycline concentrations resulted in more pronounced inhibition of growth than either drug alone. The higher activity of penicillin/cephalothin in combination with rolitetracycline on some E. coli and S. aureus strains might be due to a better access of rolitetracycline into bacterial cells whose cell walls have been weakened by cell wall-active, bactericidal drugs. Thus, growth of penicillin-induced spheroplasts of E. coli and stable staphylococcal L-forms was inhibited by much lower concentrations of rolitetracycline than were the corresponding parent cells with intact cell walls.


The LH/FSH ratio under basal conditions and after stimulation with GnRH in subjects with primary hypogonadism.

The authors have studied LH and FSH behaviour under basal conditions and after stimulation with GnRH in groups of subjects associated by the common denominator of more or less marked compromission of gonadal activity (subjects of both sexes in old age, affected by Sertoli cells only, Klinefelter's and Turner's syndromes ans subjects with congenital anorchia or with rudimentary testes) and have compared such behaviour with that shown by control groups. Special importance was given to the behaviour of LH/FSH ratio, which is significantly reduced in almost all the situations studied. To conclude, from the results obtained, the authors have evidence new elements to better single out the mechanism of homeostatic regulation of gonadotropic incretory system, with special consideration for what happens to FSH, and also useful indications to emphasize the semeiological use of LH/FSH ratio relevant to basal values and chiefly to incretory areas.


[Gonadotropins before and after LHRH in male infertility (259 cases) (author's transl)].

In primary hypogonadism (n=73) FSH basal levels and responses are elevated. LH basal levels and/or responses are elevated in 68 cases. In idiophatic oligospermia FSH and/or response are elevated in 28% cases, normal in 68% cases, decreased in 4% cases. LH and/or LH response are elevated in 44% cases normal in 53% cases and decreased in 4% cases. High significant correlation is found between FSH basal levels and FSH response, and between FSH and LH response.


Effect of osmolality on the response of Escherichia coli to mecillinam.

The influence of osmolality on the effect of the novel beta-lactam antibiotic, mecillinam, on Escherichia coli was examined in a turbidimetric system. Both sucrose and sodium chloride were able to protect E. coli from the effects of mecillinam during the stage of conversion to morphologically abnormal forms, and the additional presence of small amounts of magnesium sulfate protected the spherical forms from subsequent lysis. More phenotypically "resistant" survivors were recovered in osmotically protective media than in broth of low osmolality. Sucrose appeared a better protective agent than sodium chloride, but growth of the phenotypically resistant population was much slower in the sucrose-containing than in sodium chloride-containing medium.


Ticarcillin in combination with cephalothin or gentamicin as empiric antibiotic therapy in granulocytopenic cancer patients.

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although Staphylococcus aureus was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by S. aureus but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.


In vitro activity of gentamicin, amikacin and netilmicin alone and in combination with carbenicillin against Serratia marcescens.

The inhibitory and bactericidal effects of gentamicin, amikacin, netilmicin (Sch 20569), and carbenicillin were tested against 55 clinical isolates of Serratia marcescens that had been subtyped into 26 strains by biotyping and serotyping. Three major patterns of resistance to gentamicin, netilmicin, and carbenicillin were recognized among these isolates. (i) Most of the 27 isolates that were susceptible to gentamicin (minimal bactericidal concentration [MBC] </=6.25 mug/ml) were susceptible to carbenicillin (MBC </=125 mug/ml) and resistant to netilmicin (MBC >/=12.5 mug/ml). (ii) Most of the 11 isolates with moderate resistance to gentamicin (MBC of 12.5 to 25 mug/ml) were also susceptible to carbenicillin and resistant to netilmicin. (iii) The 17 isolates with high-level resistance to gentamicin (MBC >/= 50 mug/ml) were all highly resistant to carbenicillin (MBC >/=8,000 mug/ml) but susceptible to netilmicin (MBC </=6.25 mug/ml). The susceptibility to amikacin was unpredictable among these groups of isolates but, overall, 80% of the isolates were killed by 25 mug of amikacin/ml, which is within the range of peak serum concentrations used therapeutically. Clinically attainable subinhibitory concentrations of carbenicillin enhanced the activity of the three aminoglycosides against all isolates with MBCs of carbenicillin </=2,000 mug/ml. The 17 isolates with high-level resistance to carbenicillin and gentamicin, as well as the four isolates with high-level resistance to carbenicillin but not to gentamicin, were not susceptible to such enhancement of aminoglycoside activity by carbenicillin.


Effect of clindamycin on aminoglycoside activity in a murine model of invasive Escherichia coli infection.

Previous studies have demonstrated that the early in vitro bactericidal activity of gentamicin and amikacin is inhibited by clindamycin. To investigate the possible clinical implications of these findings, the effect of clindamycin in combination with gentamicin or amikacin was compared with that of the aminoglycoside alone in the treatment of normal and neutropenic mice with Escherichia coli peritonitis and bacteremia. Mice treated with saline or clindamycin alone experienced rapid multiplication of bacteria in the peritoneal cavity, bacteremia, and subsequent death. Gentamicin or amikacin given 2 h after E. coli inoculation significantly reduced the mortality and peritoneal bacterial counts in normal and neutropenic mice in comparison with untreated controls. Prior or simultaneous administration of clindamycin with either aminoglycoside did not inhibit survival or bacterial clearance from the peritoneum. The only clindamycin effect was slight enhancement of survival of neutropenic mice treated with multiple doses of amikacin and clindamycin in comparison to those treated with amikacin alone.


Comparison of josamycin and erythromycin in the therapy of Mycoplasma pneumoniae pneumonia.

A controlled, double-blind study was performed to compare the efficacy of two macrolide antibiotics, erythromycin and josamycin, in the therapy of Mycoplasma pneumoniae pneumonia. Marine Corps recruit volunteers received one of the two antibiotics in a dosage of 2 g daily for 7 days. Twelve of 21 men treated with josamycin and 9 of 25 men treated with erythromycin had confirmed M. pneumoniae pneumonia. The josamycin-treated group remained hospitalized for 5.4 +/- 1.2 days compared to 5.1 +/- 2.0 days for the erythromycin-treated group (0.60 > P > 0.50). Fever days were similar for the josamycin-treated (1.4 +/- 0.4) and erythromycin-treated (1.2 +/- 0.3) groups (P = 0.95). There was no difference in resolution of signs and symptoms of illness in the two study populations. Thus, josamycin is as efficacious as erythromycin in the therapy of M. pneumoniae pneumonia.


Bacteriocin production by group a streptococcal L-forms.

L-forms induced from a bacteriocin-producing strain of group A streptococcus retained both the ability to produce the streptococcin and producer strain immunity to the homologous bacteriocin. L-forms of a spontaneously cured (bacteriocin negative) derivative of this same strain failed to produce streptococcin but were sensitive to its action.


Midline cutaneous and spinal defects. Midline cutaneous abnormalities associated with occult spinal disorders.

Failure of separation of the neuroectoderm from the epithellal ectoderm to proceed in an orderly and complete fashion results in a wide variety of defects involving the skin, spinal cord, and cauda equina, as well as the surrounding structures of mesodermal origin. Congenital dermal sinuses occur most commonly in the lumbosacral region, are usually associated with a spina bifida, and may connect the skin directly to the spinal canal. Epidermoid or dermoid cysts may form at any point along a dermal sinus. Four types of cutaneous or subcutaneous abnormalities commonly seen associated with occult spinal disorders are abnormal hair, angioma, lipoma, and dimple. It is essential that these lesions are investigated at an early age, since surgical excision may prevent future neurologic deficits.


Multicenter trial analysis. Fluocinonide and betamethasone gel in psoriasis.

The relative efficacy of fluocinonide and betamethasone benzoate gels in treating the symptoms of psoriasis was evaluated in 335 patients, of whom 263 were analyzable. By means of a paired comparison design in which both drugs were examined simultaneously in the same patient, many potential sources of variation were eliminated. In addition, the analysis took into account the difficulties of pooling results in a multicenter trial. Imposing a rigorous grouping structure on the results from individual clinics minimized differences between clinics and demonstrated consistently high, statistically significant results in favor of fluocinodine gel even when several different statistical approaches were used. Local adverse reactions related to drugs were experienced by few patients.


Unusual cells in lupus erythematosus bullae.

We saw a case of bullous lupus erythematosus (LE) in which there were pre-LE cells and hematoxylin bodies in clear bullous fluid. Pre-LE cells are degenerated leukocytes with pyknotic nuclei. The diagnosis of lupus erythematosus was substantiated by immunofluorescence studies.


Use of 100 units/ml insulin in treatment of diabetic children.

The three traditional concentrations in which European insulins are prepared for therapeutic purposes often hinder understanding, sometimes cause accidents and occasionally disaster. When syringes other than the BS1619 are used the risks are increased. Insulin preparations containing 100 units/ml used with syringes graduated to contain one unit in one division (e.g. a tuberculin syringe) have been tested as part of a trial organized by the British Diabetic Association. Parents preferred the new system, which facilitated learning and reduced the possibility of error.


Esch. coli infections in childhood. Significance of bacterial virulence and immune defence.

The Esch. coli harboured in the gut constitute a reservoir of potential pathogens in the infant and child. The conditions required for these intestinal inhabitants to cause infection are not well understood. The presence of virulence factors such as capsular antigens, especially K1, may be of significance for the ability of Esch. coli to cause neonatal meningitis. The capacity of certain Esch. coli to attach to epithelial cells of mucous membranes may be important for their infective powers in the urinary as well as the intestinal tract. Furthermore, the ability of certain Esch. coli to produce enterotoxins similar to that of V. cholerae is of importance for their capacity to provoke diarrhoea. The importance of the immune defence mechanisms for prevention of these Esch. coli infections is suggested, especially in the form of local immunity provided by secretory IgA antibodies. Such antibodies directed against Esch. coli O and K antigens as well as enterotoxins are present in large amounts in human milk and may be of considerable importance for protection against Esch. coli in the breast-fed baby. Breast feeding may be of special significance until the baby has built up its own local immune defence preventing the micro-organisms from attaching to and invading the intestinal mucous membranes. SIgA antibodies in urine may have a similar protective effect against urinary tract infections. The variable pictures of Esch. coli infections in childhood are striking, ranging from severe sepsis/meningitis or diarrhoea to "asymptomatic" bacteriuria. This variability is obviously closely connected with the presence of various virulence factors and the function of different components of the immune defence.


Treponema pallidum in early syphilitic lesions in humans during high-dosage penicillin therapy. An electron microscopical study.

The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views. By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established. Before treatment started, the majority of treponemes was of intercellular localization. In the course of treatment various forms of destruction could be differentiated. The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes. 24 h after the beginning of treatment, treponemes could not be demonstrated any more. The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie.


Absence of leukocyte-migration inhibitory factor in serum from patients with mycosis fungoides.

Sera from 16 patients with mycosis fungoides at various stages of the disease were investigated for the presence of a leukocyte-migration inhibitory factor. The agarose gel techinque with human peripheral blood leukocytes as migrating indicator cells was used for the purpose. The migration inhibitory effect of patients sera, pooled AB-sera and sera from control persons was tested on peripheral blood leukocytes from patients and controls. Also upconcentrated sera were used. The presence of substances with migration inhibitory effect in serum from patients with mycosis fungoides could not be demonstrated. The significance of these findings is discussed.


[Dermatoses with transepithelial perforation (author's transl)].

The histologic concept of epidermal elimination of particulate matter was formulated by Pinkus in 1954. Mehregan enlarged on this by recognizing its fundamental role in a variety of skin diseases. The importance of this epidermal reaction pattern in five "perforating" dermatoses is stressed. Also, it is shown that active participation of the corium and epithelio-mesenchymal interaction are required for the iniation of this mechanism. The histological differentiation and histogenesis of the presented dermatoses are discussed.


Naproxen in rheumatoid arthritis. Extended trial.

121 patients with active rheumatoid arthritis, 91 of whom had proved intolerant of other nonsteroidal anti-inflammatory agents, were treated for a mean of 10 months with naproxen. A dosage of 250 mg twice daily produced sustained improvement in most of the standard clinical measurements. 28 patients complained of side effects, with a lower than expected incidence of gastrointestinal complaints and no drug-induced rash being recorded. 19 patients withdrew from the trial because of side effects, while a further 22 withdrew because the drug was ineffective. Naproxen is a useful drug for long-term use in patients with rheumatoid arthritis, including those who have proved intolerant of or experienced inadequate symptomatic relief from other nonsteriodal anti-inflammatory agents.


Voyeurism: a review of literature.

The most striking thing about the literature on voyeurism is the relative lack of material in print. In the present work, the author was able to find only 15 articles and no books that deal specifically with voyeurism. Of the 57 references compiled for this review, not one involves an experimental manipulation of variables. An attempt is made to review as many aspects of voyeurism as possible, giving illustrative case material whenever available. The areas of troilism and coprophilia are covered in some detail to establish to what degree they belong to the deviation of voyeurism. Theory of perversion has centered around the psychoanalytic and behavioral schools because of the lack of material from other approaches. The voyeur is found to be a relatively young man of low socioeconomic status, who sociosexually is said to be "not retarded but a late bloomer." He is prone to minor crimes and not major offenses. It is suggested that moyeurism be considered a deviation from normal sexual behavior and that deviations are not in and of themselves criminal behavior. At present, punishment is genera-ly mild but highly variable and unpredictable. Treatment is usually analysis or group therapy, but other forms of therapy such as aversion and avoidance conditioning are being attempted with increasing success.


[Interactions between various transition elements in their effect on pepsin activity].

Kinetic experiments were made with pepsin in the presence of Cu2+ ions and additional Fe2+, Ni2+ or Zn3+ ions as sulphates. As a parameter of the pepsin activity the turnover-rate curves were determined with haemoglobin as a substrate. An important activation of the pepsin was obtained by Cu2+ additions of 5-10(-4) mole/1. When Cu2+ and Fe2+ ions were added to the reaction mixture at the same time, an additive effect of both metal cations was observed. A competitive effect of both metal cations was found in the combination of Cu2+/Ni2+ ions. Zn2+ addition did not influence the activation of pepsin caused by Cu2+ ions.


Time -- a key in experimental and practical medicine.

This paper gives an overview on circadian rhythms which governs visibly all biological features. By illustrative examples of circadian rhythms of man and experimental animals it is shown that: 1. The components of all tissues, organs, and blood undergo circadian changes, manifested in drmatic morphologic and chemical differences. These circadian changes simply do not represent minute "physiologic" variations around a 24-h means. 2. The endogenous nature and the influences of the environmental factors such as food, light, laboratory stress, and seasons acting on circadian rhythms are demonstrated. 3. The different circadian phases determine significantly the in vivo and in vitro results in response to hormones, drugs and poisons. The neccessity to consider circadian rhythms is shown by chronotoxicologic experiments: mortality rates between 0 and 100% may occur after application of identical doses of a given drug at different day times.


New aspects of human chronopharmacology.

Regular and thus predictable changes in biologic susceptibility and response to a large variety of physical as well as chemical agents can now be viewed as a rather common phenomenon. Chronopharmacology involves both the investigation of drug effects as a function of biologic timing and the investigation of drug effects upon rhythm characteristics. Illustrative examples of circadian chronopharmacolgy in man are discussed, keeping in mind that the objective demonstration of chronopharmacologic facts needs the use of an appropriate methodology. Circadian changes in the effects of various chemical agents have been documented: histamine, sodium  salicylate, acetylcholine, halothane, prostaglandine F, reserpine, cyproheptadine, ethanol, insulin, chlorothiazide, oxymetholone, orciprenalin and SCH 1000 (bronchodilators), indomethacin, ACTH, cortisol and various synthetic corticosteroids. (three new concepts have to be considered: a. The Chronokinetic of a Drug. This term includes both rhythmic changes in the drug vioavailability, pharmacokinetic and its excretion. b. The Chronesthesy of a Biosystem to a Drug. i.e. circadian changes in the susceptibility of any biosystem to a drug. c. The Chronergy of a Drug, taking into consideration its chronokinetic and the chronesthesies of the involved organismic biosystems. Chronopharmacology is useful to solve problems of drug optimization, i.e. to enhance the desired effeciency or to reduce its undesired effects. In the human organism (among other animal species) the metabolic fate of a pharmacologic agent (as well as that of a nutrient) is not constant as a function of time. Thus, the chronobiologic approach of pharmacologic phenomena involves a lesser risk of errors and/or false information than the conventional homeostatic approach.


[Clinical studies on the tolerance of a new antibiotic combination, pivampicillin and dicloxacillin].

The tolerance of a new pivampicillin and dicloxacillin association, especially at high doses and during prolonged treatment, was assessed by administering two 600 mg tablets (350 mg pivampicillin + 250 mg dicloxacillin) every 6 or 8 hr (according to the seriousness of the diseases) to 53 patients with acute infection of varying site and aetiology. Microbiological, radiological and blood chemistry data were collected with reference to the disease involved, along with clinical and laboratory data capable of demonstrating the eventual appearance of unwanted side-effects referable to the association. The results showed that the association was therapeutically effective and well tolerated at high doses given over long periods.


[Operative treatment of distal tibial fractures. Technique of osteosynthesis and results in 128 patients (author's transl)].

Fractures of the distal tibia including the articular surfaces have considerably increased. A simple classification based on the surgical findings is recommended and some particular diagnostic criteria are pointed out. The operative approach and technique have been described in detail. Due to special osteosynthetic implants alignment of the axis, anatomical reconstruction of the articular surfaces, and stabilisation in comminuted fractures has been greatly facilitated. Cancellous bone from the ipsilateral proximal tibia is advantageous for the filling of metaphyseal defects in juvenile patients. Post-operative treatment has to be individualized with emphasis on functional treatment. Between 1963 and 1973, 128 osteosynthetic reconstructions for fracture of the distal tibia have been performed. Primary fusion was not necessary in any patients. 121 patients could be reviewed an average of 4 years after injury. Late complications (delayed healing, refracture, late infection etc.) were rare (about 7%) and healed without further sequelae. Secondary correction of the axis or fusions were not required. In 90% the functional results after these serious fractures were good. 85% returned to athletic activity, only 5% are disabled.


Immunofluorescence studies on pathologic routine material: application to malignant lymphomas.

In an attempt to apply immunmorphologic techniques to pathologic routine material, malignant lymphomas of the Non-Hodgkin- and the Hodgkin-type were studied by indirect immunofluorescence. To minimize nonspecific background staining formalin fixed paraffin sections were treated with protease prior to incubation with the antisera. The usefullness of this procedure in providing additional diagnostic criteria was tested on specimens of malignant lymphomas (chronic lymphocytic leukemias, immunocytic lymphomas, plasmocytic lymphomas, centrocytic lymphomas, centroblastic-centrocyctic lymphomas, centroblastic lymphomas, immunoblastic lymphomas, lymphoblastic lymphomas of Burkitt, convoluted and unclassified type, Hodgkin's disease). In addition, cases of nonspecific lymphadenitis were studied. The discrimination of single cells particularly of the B-cell line was facilitated using immunofluorescence and different patterns were easily recognized thus aiding the diagnosis based on light microscopic criteria. In addition, preliminary evidence was obtained that lymphoblastic lymphomas categorized as "others" may be further characterized.


[Blood groups of human fossil remains].

The results of the blood grouping of the fossil human bones, from different mesolyte necropoles, are presented. These results, giving the informations concerning biological individualities of the ancestors of our country, will be of great importance for anthropology and ethnology of this region.


Amino acid differences between the alpha-chains from two hemoglobins of the yellow-cheeked vole (Family Cricetidae).

The yellow-cheeked vole (Microtus xanthognathus) shows two electrophoretic hemoglobin components. Electrophoresis of the polypeptide chains from the separated hemoglobin components shows identical beta-chains but two alpha-chains of different mobility, alphaf and alphas. The composition of soluble tryptic peptides was determined for each alpha-chain. Amino acid differences were found in peptides alpha T1 and alpha T9; the compositions of the remainder of the homologous peptides were identical. Differences in alpha T1, found at alpha4 (alpha2-Gly-alphaf-Val) and alpha 5 (alphas-Thr-alphaf-Asp), were confirmed after a run to residue 20 of the fast component in an automatic sequencer. The differences in charge between alphaT1 peptides can account for the electrophoretic pattern of two hemoglobins. This is the first time that it has been possible to identity the residues which can account for the charge difference between the two hemoglobins observed in a Microtus species.


The aminoacylation of transfer ribonucleic acid. Inhibitory effects of some amino acid analogues with altered side chains.

Several amino acid analogues that are able to replace amino acid residues in binding positions of the biologically active C-terminal tetrapeptide amide sequence, Trp-Met-Asp-PheNH2, of the gastrins were examined for their ability to inhibit the aminoacylation of tRNA in an Escherichia coli and rat liver system. Although in both systems the amino acid side chains are involved in the recognition process, the structural requirements of the side chain in the two systems are not comparable. Analogues of methionine and phenylalanine behaved similarly in the E. coli and rat liver systems, whereas analogues of tryptophan behaved differently. From the results it is possible to suggest structural features of the amino acid side chains which are required for recognition by the aminoacyl-tRNA synthetases.


Evidence for two lipoic acid residues per lipoate acetyltransferase chain in the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

The reaction of two maleimides, N-ethylmaleimide and bis-(N-maleimidomethyl) ether, with the pyruvate dehydrogenase multienzyme complex of Escherichia coli in the presence of the substrate, pyruvate, was examined. In both cases, the reaction was demonstrated to be almost exclusively with the lipoate acetyltransferase component, and evidence is presented to show that the most likely sites of reaction are the lipoic acid residues covalently bound to this component. With both reagents the stoicheiometry of the reaction was measured: 2 mol of reagent reacted with each polypeptide chain of lipoate acetyltransferase, implying that each chain bears two functionally active lipolic acid residues. This observation can be reconciled with previous determinations of the lipoic acid content of the complex by allowing for the variability of the subunit polypeptide-chain ratio that can be demonstrated for this multimeric enzyme.


Glycosylation in vitro of an asparagine sequon catalysed by preparations of yeast cell membranes.

Preparations of yeast cell membranes can catalyse in vitro the N-acetyl-beta-D-glucosaminylation of the asparagine sequon at residues 34--36 of bovine pancreatic ribonuclease A. The relevant glycopeptides were isolated from tryptic hydrolysates of the glycosylated ribonuclease and analysed. The donor used was UDP-N-acetyl-D-glucosamine, although the mechanism of the transfer is unknown. Mn2+ ions at concentrations of 25 mM double the activity of the enzymic transfer.


A model for cytoplasm-governed gene regulation.

A model of cytoplasm-governed transcription is presented. The nuclear membrane has a selective permeability towards nuclear pre-mRNA molecules which are provided with group-specific non-translated "passwords". RNA transcription on the chromatin proceeds under a dual control. One of them is gene regulation according to the Britten-Davidson and Georgiev models. The other is cytoplasm-governed regulation mediated through the selective transport of mRNA from nucleus to cytoplasm. Pre-mRNA molecules which are not "in immediate demand" by the cytoplasm and therefore accumulating the nucleus repress their own synthesis by end-product inhibition. The interrelationship of the two types of regulation in the course of cell development is discussed.


Competition between trichodermin and several other sesquiterpene antibiotics for binding to their receptor site(s) on eukaryotic ribosomes.

1. Of the five sesquiterpene antibiotics tested and found to inhibit protein synthesis in yeast spheroplasts, trichothecin, trichodermol or trichodermin stabilized polyribosomes whereas, in contrast, verrucarin A or T-2 toxin induced 'run off' of polyribosomes with a corresponding increase in 80S monoribosomes. The effect of fusarenon X on the system could not be determined as the drug failed to enter the cells. 2. [acetyl-14C]Trichodermin bound to yeast polyribosomes with a dissociation constant of 2.10 muM and to yeast 'run off' ribosomes with a dissociation constant of 0.72 muM. 3. Trichothecin, trichodermol, fusarenon X, T-2 toxin and verrucarin A competed with [acetyl-14C]trichodermin for binding to its receptor site on 'run off' ribosomes. The observed competition was quantitatively similar for all drugs tested. In contrast, the five drugs competed to different extents with trichodermin for binding to its receptor site on polyribosomes. Thus trichothecin competed with relative efficiency, whereas verrucarin A competed poorly, and the other drugs occupied intermediate positions between these two extremes. 4. Studies were also carried out with yeast 'run off' ribosomes prepared from both a wild-type strain and a strain resistant to trichodermin. Competition experiments between verrucarin A and [3H]anisomycin indicated that verrucarin A bound to 'run off' ribosomes from the mutant strain less efficiently than to those from the wild-type.


Polypeptide-chain-elongation rate in Escherichia coli B/r as a function of growth rate.

By evaluating the kinetics of radioactive labelling of nascent and finished polypeptides, the peptide-chain elongation rate for Escherichia coli B/r at three different growth rates (mu) was determined to be 17 amino acids/s for the fast-growing cells (mu equals 1.3 and 2.0 doublings/h) and 12 amino acids/s for slow-growing cells (mu equals 0.67 doublings/h). The results agree with the growth-rate-dependence of the rate of peptide-chain elongation found for the translation of newly induced beta-galactosidase messenger in this strain and under these conditions of growth [Dalbow & Young (1975) Biochem. J. 150, 13-20]. Together with the previously observed ribosome efficiency at these growth rates [Dennis & Bremer (1974) J. Mol. Biol. 84, 407-422] the results indicate that the fraction of ribosomes engaged in protein synthesis is about 0.8 at all three growth rates.


[Multicentre-clinical trial of the novel corticosteroid diflucortolone valerate in the forms of cream, ointment and fatty ointment. Part I: Comparative study of diflucortolone valerate with fluocortolone, -capronate, -pivalate in a double-blind contralateral design with topical application (author's transl)].

6alpha,9-Difluor-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) 0.1% as a cream, ointment and fatty ointment was investigated in a double-blind contralateral design in 925 patients in comparison to fluocortolone (Ultralan), fluocortolone caproate and fluocortolone pivalate in three concurrently performed studies. The results of the contralateral study show Nerisona cream and ointment to be more effective (P less than 0.01) than Ultralan. The fatty ointment was also superior, but the difference was statistically significant (P less than 0.05) only in the indication psoriasis. No differences could be established in the less sensitive absolute assessment. The therapeutic success rate of 76-92% according to strict criteria-only complete healing and distinct improvement were counted as a success-clearly demonstrates the efficacy of the preparations. The local side effects recorded-mainly irritation and burning- were of a mild nature.


[Multicentre-clinical trial of the novel corticosteroid diflucortolone valerate in the forms of cream, ointment and fatty ointment. Part II: Comparative study with several commercial preparations (author's transl)].

6alpha,9-Difluoro-11beta-hydroxy-16alpha-methyl-21-valeryloxy-1,4-pregnadiene-3,20-dione (diflucortolone valerate, Nerisona) in the forms of cream, ointment and fatty ointment was investigated against 5 commercial preparations with beta-methasone-17-valerate, fluocinonide, fluocinolone acetonide, flumetasone pivalate and desoximetasone in 15 simultaneously conducted and multicentre-clinical studies-all on double-blind contralateral studies-involving a total of 1923 patients. The Nerisona preparations proved to be highly effective-particularly in eczematous diseases- and comparable to the above-mentioned commercial preparations. Nerisona ointment was shown to be superior to flumetasone cream. The statistical reliability of such data is discussed.


[Chemotherapeutically active nitro compounds. 2nd communication: Nitrodiphenyl sulfones (author's transl)].

A number of new 4-nitro-4'-amino-diphenyl sulfones and related compounds were prepared and investigated as to their therapeutic activity. They showed a good systemic activity against tubercle bacilli (M. bovis, NMRI mouse) and plasmodia (P. berghei, NMRI mouse). The test results reveal that the 4-nitro-4'-amino-diphenyl sulfones possess a spectrum of activity similar to that of diamino-diphenyl sulfone (DDS). It is assumed that 4-nitro-4'-amino-diphenyl sulfones in vivo are converted into DDS derivatives by reduction. The advantages of the new compounds, however, were too insignificant as compared to DDS to justify further extensive trials.


[A time-saving method for histo-enzymatic studies of brain tissues of animals with chronically implanted electrodes by means of a hard-section microtome (author's transl)].

A time-saving method is described for the localisation of chronically implanted electrodes in the brain of test animals by means of a "Kryostat" hard section microtome which allows both histo-topographic and histo-enzymatic investigations. This is made possible by the incorporation of a three-dimensional microtome holder.


[Results of a field study on the therapeutic value of aprotinin in traumatic shock (author's transl)].

In the years 1971 to 1973 the therapeutic effect of Trasylol (aprotinin isolated from bovine organs) in the treatment of the traumatic shock was investigated in a controlled field study at 31 hospitals in northern Germany. The study included 4686 patients. There could be proved a significant reduction in letality by Trasylol treatment even under the broad conditions of general field application. The therapeutic activity of Trasylol was most efficient when Trasylol was applied within 30 min after the trauma and consists especially of a better prognostic for further development. The letality after 12 h is remarkably reduced by an early application of Trasylol and posttraumatic surgical operations have a significantly lower risk.


Changes of simple somatic parameters by delta-9-trans-tetrahydrocannabinol (delta-9-THC) in a double-blind-study. Short communication.

The effects of 250 mug/kg delta-9-trans-tetrahydrocannabinol (delta-9-THC) p.o. on several somatic parameters were assessed in a double-blind study on 36 volunteers. The consistently reported increase of the pulse rate was confirmed. In other somatic variables no differences to placebo were found. There were, however, significant correlations between the intensity of affective changes under delta-9-THC and the rise of eosinophilic granulocytes.


Double-blind investigation of two corticoid preparations for the treatment of eczematous skin disorders. Short communication.

In a double blind fully randomised trial, three Belgian dermatologists independently treated 81 patients suffering from various eczematous skin disorders. After four weeks both the dermatologists and their patients assessed the results of a twice-daily topical application of an ointment containing 17 beta-hydroxy-4-estren-3-one-17-decanoate (nandrolone decanoate, Dexatopic) ointment or a reference ointment. Both the dermatologists' and the patients' assessments of the two preparations showed that there was no significant difference between the two treatments although Dexatopic did seem to have a more favourable profile in the "much improved" area. In the total score decrease, there was an indication that Dexatopic had a more favourable effect than the reference preparation.


A double-blind cross-over evaluation of the activity of d-oxazepam hemisuccinate sodium salt (D-7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-2H-1,4-benzodiazepine-2-one) compared to its racemic form.

After carrying out a pilot study on D-7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-2H-1,4-benzodiaze-pine-2-one (D-oxazepam hemisuccinate sodium salt) (+), the authors examined in the present study the anxiolytic effects of this drug in comparison to its racemic form (+/-). The modifications of the symptoms were measured by the rating scale for anxiety (R.S.A.S.) of Hamilton and the experiment was carried out according to a cross-over, double-blind design. 34 patients hospitalized in the Psychiatric Hospital of Marzana (Verona) were studied. These patients complained of different syndromes but each of them had anxiety as the main symptom. The results obtained, evaluated clinically and statistically, confirm what was previously reported on the activity of D-oxazepam hemisuccinate sodium salt. In synthesis the drug given at a daily dose of 100 mg i.m. acts favourably upon: sleep disturbances, anxiety states and tension, somatic symptoms associated with anxiety. Given in equal doses both substances, dextrorotatory and racemic forms, act upon the same parameters of anxiety (as reported above). It has a superior activity over the racemic form, as it can be seen by the comparison of the variations of the general symptomatology and the single items particularly in the 2nd cycle of treatment.


Antilipolytic therapy in angina pectoris. Reduction of exercise-induced ST segment depression.

A double-blind cross-over study was performed on 12 men sith stable angina pectoris in order to determine the effect of antilipolytic treatment on exercise tolerance and exercise-induced electrocardiographic changes. The men were exercised to the onset of anginal pain using a reproducible and standardized ergometric load. A nicotinic acid analogue was used to reduce plasma free fatty acids and free glycerol before and during exercise testing and to eliminate their post-exercise rise. This was associated with significant reduction of exercise-induced ST segment depression (p less than 0-005), though there was no significant difference in the duration of exercise before the oneset of pain. A change in the prportions of lipid and carbohydrate for oxidation by the ischaemic myocardium, making relatively more glucose available, is a likely explanation.


Closure of pericardium after open heart surgery. A way to prevent postoperative cardiac tamponade.

Between July 1968 and December 1975, 821 patients underwent open heart operations. In 596 cases the pericardium was left open and in 225 the pericardium was closed. Forty-one patients in the open pericardium group required reoperation and 23 of these had tamponade. Four patients in the closed pericardium group had reoperation but there was not a single case of tamponade. In most cases that required reoperation the bleeding was from extrapericardial sources. Absence of tamponade in the closed pericardium group can be explained by the fact that blood from extrapericardial sources of bleeding cannot collect round the heart because the pericardium is closed. Thus closure of pericardium helps to prevent tamponade. Reoperations some months or years after the original operation are technically easier and less hazardous if the pericardium has been closed because the closed pericardium prevents the heart from becoming adherent to the back of sternum and also because there are fewer adhesions in the pericardial cavity.


Cholesterol-lowering effect of colestipol hydrochloride given twice daily in hypercholesterolemic patients.

In a randomized design study in 66 hypercholesterolemic patients, dosages of 10 g of colestipol HCl twice daily lowered serum cholesterol an average of 19% more than placebo therapy. These results are comparable to those in other studies in which the same total daily dose was given in three or four doses. The most common side effect was constipation, reported by 6 patients on colestipol HCl and 3 patients on placebo. No untoward systemic reactions or abnormal laboratory data were seen except for a slight rise in serum alkaline phosphatase during colestipol HCl therapy. The drug was well accepted by most patients.


Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design.

The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers, reporting the results in the medical literature. One unreported result which deserves such publication is the development of the expertise to design and analyse such trials. This report was prepared by a group of British and American statisticians, but it is intended for people without any statistical expertise. Part I, which appears in this issue, discusses the design of such trials; Part II, which will appear separately in the January 1977 issue of the Journal, gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test, including a worked example, and discusses the interpretation of trial results, including brief reports of 2 particular trials. Both parts of this report are relevant to all clinical trials which study time to death, and wound be equally relevant to clinical trials which study time to other particular classes of untoward event: first stroke, perhaps, or first relapse, metastasis, disease recurrence, thrombosis, transplant rejection, or death from a particular cause. Part I, in this issue, collects together ideas that have mostly already appeared in the medical literature, but Part II, next month, is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration. Such trials include the majority of all clinical trials of cancer therapy; in cancer trials,however, it may be preferable to use these statistical methods to study time to local recurrence of tumour, or to study time to detectable metastatic spread, in addition to studying total survival. Solid tumours can be staged at diagnosis; if this, or any other available information in some other disease is an important determinant of outcome, it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive, and more intuitively satisfactory, for it will then only be necessary to compare like with like, and not, by chance, Stage I with Stage III.


A lysosomal storage disorder of the epidermis characterized by a deficiency of alpha-mannosidase and an accumulation of mannose-rich materials.

Laboratory investigation of a patient diagnosed as ichthyosiform erythroderma bullosa revealed the following abnormalities: (1) alpha- and beta-galactosidases were elevated in the lesion. (2) alpha-mannosidase activity was extremely low both in the lesion and in relatively normal epidermis. (3) The mannose:glucose ratio of water-soluble hexose-containing material in the scales was very high. (4) Membrane-limited vacuoles, apparently enlarged secondary lysosomes, were observed. We conclude that this patients is the first documented example of a lysosomal storage disease in which overt clinical lesions are confined to the epidermis.


Relapse rate of psoriasis worsened by adding steroids to a dithranol regime.

The rate of relapse after dithranol therapy is significantly less that when betamethasone valerate under occlusion is combined with ditrhanol in the treatment of psoriasis. It is also argued that local steroids are inferior to deithranol in the management of psoriasis.


T cell variant of chronic lymphocytic leukaemia with chromosome abnormality and defective response to mitogens.

Lymphocytes from a patient with chronic lymphocytic leukaemia, in whom therapy was ineffective, were defined as thymus-derived (T) cells by membrane markers (sheep erythrocyte rosettes, complement rosettes, surface immunoglobulin). The lymphocytes responded weakly to two mitogens, phytohaemagglutinin and the calcium ionophore A23187, but not to concanavalin A. Cytogenetic studies of leukaemic cells from unstimulated and mitogen-stimulated cultures revealed an abnormal karyotype with 45 chromosomes and multiple rearrangements. The T cell variant of classical chronic lymphocytic leukaemia is relatively rare; additional reports are needed to determine if the clinical course is typically less benign than in the common B cell variety, or whether this patient simply represented a late, unresponsive phase of the disease.


Perinatal infections by group B beta-haemolytic streptococci.

Since 1970 there has been an increase in isolations of Group B beta-haemolytic streptococci from infants and mothers at the National Women's Hospital and the organism has become the major cause of fatal perinatal infection. Forty-three of 60 stillborn and liveborn infants with postmortem isolations of Group B streptococci had pneumonia and of these a minority also had meningitis and/or septicaemia. Amnionitis was found in 15 of 20 placentae examined from these patients and an ascending infection from the maternal genital tract, often through intact membranes, was considered likely in the majority. However, a review of the prenatal histories of 33 infants showed that only a minority had premonitory features such as prolonged rupture of membranes, prolonged labour or maternal fever. Thirteen of 26 liveborn infants had a birth weight less than 2500 g. The majority presented within one hour of birth with respiratory distress or apnoea and died within 48 hours of birth. Early diagnosis of Group B infection is possible if bacteriological and radiological evidence is sought in infants of low birth weight, with low Apgar scores and with early onset of respiratory distress syndrome or apnoea in addition to those having the more usual indications of intrauterine infection. Group B streptococci were carried vaginally in 9 per cent of women attending an antenatal clinic and this high carrier rate is considered to preclude prophylactic treatment.


Early dose response analysis of ocular hypotensive effects of propranolol in patients with ocular hypertension.

Placebo and propranolol (Inderal) in doses of 20, 40, and 80 mg were given in a single-blind test to two groups of six ocular hypertensives. The groups consisted of patients with an intraocular pressure ranging from 20 to 29 mmHg and 30 to 39 mmHg. The doses were given 48 hours apart and administered after fasting 12 hours. IOP by Goldmann applanation tonometer, systemic blood pressure and pulse rate in the supine position were recorded hourly before and after administration. In both groups a decrease in mean IOP was noted after one hour and this reduction reached its maximum three hours after the administration of propranolol. The absolute reduction was greater in the group with the highest initial IOP and in both groups the fall in mean IOP showed a clear dose-dependent correlation. The simultaneous mean decrease in pulse rate was also dose-correlated, but reached its maximum two hours after administration. The fall in systemic blood pressure was only moderate and showed no obvious dose-dependence.


Atrophy of the mandible: reconstruction following fracture.

A rational approach to the management of spontaneous fracture of the severely atrophie mandible is illustrated by means of a case report. A study of the literature reveals that some confusion exists concerning the terms "atrophy" and "osteolysis", and an attempt is made to distinguish between them.


The effect of RNA supplementation of rat diets on the composition of body fluids.

1. In a number of separate experiments, yeast RNA, mixtures of its constituent nucleosides, its constituent bases and ribose were administered orally to rats. In each instance, the resultant changes in the composition of body fluids were monitored using sensitive methods. 2. Ingestion of RNA (100 g/kg diet) caused detectable increases in intestinal ribose, inorganic phosphate, uridine, pseudouridine, uracil, inosine, uric acid and probably other purine bases. Their accumulation did not detectably affect the rate of passage of food along the digestive tract, even though some nucleosides are known to affect gut motility. 3. Although plasma levels of uric acid and uridine were higher when RNA was administered in the diet, these changes were very slight compared with those in plasma uracil, which in some experiments were increased more than 20-fold compared with control levels (300 mumol/l). Analysis of erythrocytes indicated that the internal environment of at least some cells of the body are similarly altered. 4. Analyses indicated that all dietary RNA-phosphate passed into the urine from the gut but most of the RNA-ribose was probably metabolized. Uracil and uric acid levels in the urine reflected plasma composition. 5. The effect of orally administered mixed nucleosides on blood and urine composition was similar to that of RNA, but the response to an equivalent mixture of free bases differed in several respects; cytosine, adenine and hypoxanthine appeared in urine only under these circumstances.


Kinetics of ribosome dissociation and subunit association studied in a light-scattering stopped-flow apparatus.

The association-dissociation kinetics of ribosomes from Escherichia coli have been studied under various conditions in a light-scattering stopped-flow apparatus. The dissociation reaction at 2 mg/ml at 25 degrees C, induced by lowering the MgCl2 concentration from 18 to 3 mM, can best be described by three independent first-order processes with rate constants of 15 s-1, 0.9 s-u, and 3 X 10(-2) s-1, the slowest process comprising about 60% of the overall reaction. The fraction of ribosomes dissociating with the fastest rate (15 s-1) is concentration dependent and becomes negligible at 0.1 mg/ml9 Ribosomes treated with puromycin also show three dissociation rates with essentially the same rate constants as the nontreated samples. The dissociation induced by a high KCl concentration (0.85 MKCl, 18 mM MgCl) also shows three first-order phases with the same rate constants as for the dissociation induced by lowering the MgCl2 concentration. The formation of 70S ribosomes from 30S and 50S subunits, induced by increasing the MgCl2 concentration from 2 to 21 mM, follows second-order biphasic kinetics. A detailed analysis of the kinetic results shows that the two principal ribosomal forms must have one type of subunit in common. When the association data are analyzed assuming that the kinetic heterogeneity arises from two forms of only one subunit, the rate constants are found to be 6.4 X 10(6) and 1.05 X 10(6) M-1 s-1.  Sequential flow experiments show that the rapid and slow association species are to be identified, respectively, with phases II (0.9 s-1) and III 0.03 s-1) of dissociation. Relaxation measurements show that these correspond to type B ("loose") and A ("tight") ribosomes, respectively. Tight and loose ribosomes were isolated by sucrose density centrifugation, and dissociation and association kinetic studies confirmed the above assignments. Furthermore, the rate constants for these ribosoems agreed within experimental error with rate constants derived from analysis of the multiphasic kinetic data. The association rate constants are for ribosomes dissociated by dilution with the appropriate buffer immediately before recording the kinetics of association. Ribosomes dissociated by dialysis overnight against 2 mM MgCl2 show an association rate constant for the slower association reaction (type-A ribosome) that is about four times smaller, whereas the rate constant for the faster process is roughly the same. The activation energies of the dissociation reactions, whether induced by lowering the MgCl2 concentration or increasing the KCl concentration, and the association raaction induced by increasing the MgCl2 concentration are less than 3.5 kcal/mol. The rate constants of the dissociation at 3 mM MgCl2 and of the association reaction at 21 mM MgCl2 do not vary between pH 7.2 and 8.4. When 30S and 50S subunits are flowed against buffer containing 20 mM spermidine, the association process is monophasic, with an association constant k - 6 X 10(6) M-1 s-1...


Physicochomecial studies on interactions between DNA and RNA polymerase. Isolation and mapping of a T7 DNA fragment containing the early promoters for Escherichia coli RNA polymerase.

The cleavage sites in the early promoter region of coliphage T7 have been mapped for four restriction enzymes. They are, from the left end in base pairs, 1100 and 740 for Hinf; 680, 320, 530, 240, 77, and 67 for Hind II; 620 and 530 for Hpa II; 790 for Alu I. The nucleotide sequence between the Hind II site at 680 base pairs from the left end and the Hinf site at 740 base pairs from the left end has been determined, from which the start point of the promoter A3 is located at 720 base pairs from the left end. The start points of the other two major promoters A1 and A2 are deduced to be at 460 and 580 base pairs from the left end, respectively, from the chain lengths of the in vitro transcripts off the 1100 base-pairs long Hinf fragment. Similar to the sequences of a pL and pR promotors of phage lambda and a sequence in Simian Virus 40 used by Escherichia coli RNA polymerase as a promotor, the sequence of the A3 promotor of T7 also has a Hind II restriction site approximately 30 base pairs upstream to the start point of RNA synthesis. No such Hind II sites exist, however, for the A1 and A2 promoters. Experiments on the protection of some of the restriction sites on the 1100 base-pairs-long Hinf fragment by RNA polymerase binding support the electron microscopic observations of others that, in addition to the three sites A1, A2 and A3, there is at least a fourth site at which E. coli RNA polymerase can bind strongly. In addition to the Hind II site at 680 base pairs from the left end and the Hinf site at 740 base pairs from the left end, which are presumably protected by the binding of a single RNA polymerase at the A3 site, the Hind II site at 240 base pairs from the left end is also protected at a level of 5 polymerase molecules/DNA fragment. The possible existence of several minor promotor sites in the early promotor region, in addition to the three major promotor sites, is discussed.


Metabolic aspects of the secretion of stored compounds from blood platelets. V. Effect of ionophore A23187 on washed platelets.

1. The A23187-induced secretion of preabsorbed serotonin from human blood platelets at 37 degrees C is studied. Preincubation at the same temperature before the addition of ionophore is necessary for maximal release induction. When total incubation time is kept constant, longer time with ionophore results in a smaller decrease in the level of metabolic ATP and increase in metabolic ATP and increase in metabolic IMP. This coincides with the reduction in secretion, but statistical treatment of the results suggests that the reduced secretion only partially explains the reduced drop in metabolic ATP, and that therefore a resynthesis of metabolic ATP from IMP may have taken place. 2. In some experiments induction of secretion takes place over a very narrow range of ionophore concentration. 3. When K+ substitutes for Na+ in the extracellular medium, the need for preincubation for maximal secretion becomes less evident, and at times is abolished, while there is still a significant increase in the metabolic ATP level by prolonged incubation with ionophore. 4. A reduction in secretion is observed with metabolic blockers when the ionophore is added after preincubation, but to a much less degree than when secretion is induced by thrombin, in spite of a great  reduction in the level of metabolic ATP. This may partly be explained by the increase in secretion induction by A23187 in the presence of inhibitors when the ionophore is added in the cold, suggesting that the inhibitor may cause "weakening" of the platelets' "resistance" to induction of secretion by ionophore. 5. When the effect of Ca2+ and of Mg2+ on the level of intermediates of the TP leads to hypoxanthine conversion is studied, it is evident that the addition of Ca2+ causes enhanced IMP accumulation and a reduction in the level of inosine plus hypoxanthine, while Mg2+ has the opposite effect. This suggests that the two metals affect the enzymes of the IMP leads to hypoxanthine conversion differently. 6. Indomethacin inhibits secretion induced by A23187, suggesting that prostaglandin intermediates may amplify the ionophore-induced release. The adenine nucleotide metabolism is not affected. 7. The results indicate that there is an indirect, rather than direct, link between the major metabolic changes and the secretion induced by A23187, but that the ionophore may cause intracellular changes which are not connected to its effect as release inducer.


Effects of dextran-linked chloromercuribenzoic acid on insulin release from microdissected pancreatic islets.

Insulin release in response to dextran-linked p-chloromercuribenzoic acid was studied in microdissected pancreatic islets of non-inbred ob/ob-mice. No contamination of the dextran-linked mercurial with free chloromercuribenzoic acid was detected before or after the incubation with islets. In comparison with free mercurial, of the same thiol-blocking activity, the dextran-linked compound had a weak insulin-releasing action with a different dose vs. response relationship. The dextran-linked mercurial had no demonstrable effect on the islet content of cyclic AMP. The results support the hypothesis that free organic mercurials mainly stimulate insulin release by blocking thiol ground that are embedded within the beta-cell plasma membranes beneath their surfaces.


Spectroscopic studies of pepsin and its complex with Streptomyces pepsin inhibitor.

Binding of Streptomyces pepsin (EC 3.4.23.1) inhibitor to the active site of pepsin causes a characteristic ultraviolet difference spectrum having a trough around 298 nm which suggests that tryptophan residue(s) are involved in a decreased refractive index or different charge density. The fluoreschat of the pepsin-inhibitor complex. Relatively large circular dichroism (CD) spectrum change at 280--310 nm was observed upon binding of the inhibitor. Solvent perturbation difference spectra of pepsin alone and the pepsin-inhibitor. Solvent perturbation difference spectra of pepsin alone and the pepsin-inhibitor complex obtained with 20% ethylene glycol as perturbant showed that the exposed 2.5 tryptophan residues were not buried upon binding of the inhibitor, whereas 1.5 tyrosine residues were buried. It is speculated that the microenvironmental change around tryptophan residue(s) which are not located at the inhibitor binding site is induced upon binding of the inhibitor.


Phosphoenolpyruvate carboxylase of Escherichia coli. Studies on multiple conformational states elicited by allosteric effectors with a fluorescent probe, 1-anilinonaphthalene-8-sulfonate.

Conformational change of phosphoenolpyruvate carboxylase (orthophosphate: oxaloacetate carboxy-lyase (phosphorylating), EC 4.1.1.31) induced by allosteric effectors was investigated using a hydrophobic probe, 1-anilinonaphthalene-8-sulfonate (ANS). Kinetic experiments suggested that ANS binds with the enzyme at the sites which are not involved in the catalytic and regulatory functions, though it partially inhibits the enzyme activity with half-saturation concentration (S0.5) of 38.5 muM. Binding experiments showed that a maximum of 2 mol of ANS are able to bind with 1 mol of the enzyme subunit presumably with an equal dissociation constant to each other (34.5 muM). Flourescence emission of ANS was markedly increased by binding with the enzyme. L-Aspartate, the allosteric inhibitor, and CoASAc and fructose 1,6-bisphosphate (Fru-1,6-P2) the allosteric activators, produced various degrees of change in fluorescence, when added singly or in combinations. The changes were shown to be attributable to the allosteric interactions between the enzyme and effectors from some criteria such as structural specificity, half-saturation concentrations, and heterotropic-homotropic interactions of the ligands. It was concluded from these analyses that the enzyme can be in at least four conformational states which are distinct from each other. Especially noteworthy is the finding that the enzyme, upon simultaneous binding of CoASAc and Fru-1,6-P2, takes a new conformation which is enterely different from those induced by sole binding of each effector. In addition, the heterotropic interaction between the activator and the inhibitor was observed through conformational change by the ANS method, as observed in the kinetic studies.


The incorporation of tritium from tritium-enriched water into UDP-N-acetylglucosamine and UDP-N-acetylmannosamine catalyzed by UDP-N-adetylglucosamine 2-epimerase from Escherichia coli.

Uridine diphosphate N-acetylglucosamine 2-epimerase from Escherichia coli 014 K7 H- catalyzes the reversible epimerization of uridine diphosphate N-acetylglucosamine to uridine diphosphate N-acetylmannosamine. During epimerization, tritium from tritium-enriched water is incorporated into both uridine diphosphate N-acetylglucosamine and uridine diphosphate N-acetylmannosamine. The position of incorporation is C-2 of the N-acetylhexosamine moieties.


Effect of genetic and physiological manipulations onthe kinetic and binding parameters of the adenine nucleotide translocator in Saccharomyces cervisiae and Candida utilis.

1. Ghe kinetic and binding parameters of adenine-nucleotide transport have been studied in mitochondria isolated from yeast cells in which the mitochondrial protein-synthetizing system had been inhibited by growth in the presence of erythromycin. These parameters have also been studied in promitochondria isolated from yeast grown in anaerobiosis aesence of ethidium bromide results in a loss of cytochromes b, alpha and alpha 3, but it does not affect the rate constant of ADP transport in isolated mitochondria, nor the number of binding sites for atractyloside, bongkrekic acid and ADP. 3. Promitochondria from S. cerevisiae grown in anaerobiosis, mitochondria from a qo mutant (qo mitochondria) and mitochondria from S. cerevisiae grown in the presence of erythromycin (ERY-mitochondria) are able to transport ADP by the same exchange-diffusion mechanism, sensitive to carboxy-atractyloside, and with the same rate constant as the wild type mitochondria. Promitochondria, qo mitochondria and ERY-mitochondria bind atractyloside, bongkrekic acid and ADP with the same high affinity as the wild type mitochondria. They only differ from the wild type mitochondria by a lower number of binding sites for ADP and for specific inhibitors of ADP transport. 4. Mitochondria isolated from the nuclear mutant p9 of S. cerevisae, called also op1, are characterized by a much lower affinity for bongkrekic acid than mitochondria from the wild type (20 times less). 5. Manipulation of the fatty acid composition of the mitochondrial membranes in the desaturase auxotroph mutant KD115 does not modify the number of sites, no their affinity of bongkrekic acid. 6. The above results are interpreted to mean that the structure and function of the mitochondrial adN translocator are not affected by any change in the mitochondrial protein synthetizing system.


[New approach to the interpretation of vibrational spectra of microbial cells].

IR-technique was applied to study baker's yeast cell and its envelope fragments. The quantitative evaluation of spectra was made using the polysaccharide band at 1070 cm-1 as the bench one. The comparison of the spectra of the whole cells and of the envelope fragments suggested that the spectrum of the yeast cell was governed by the composition of its envelope only. ATR-spectra of the whole cells and of envelope debris were obtained and the comparison of these with the "absorption" ones made it possible to conclude that the yeast cells vibration spectrum was for the most part the reflection spectrum governed by the composition of the cell envelope rather than the absorption one.


Heart rate, muscle tension, and alpha production of transcendental meditators and relaxation controls.

A group of transcendental meditators, and a group of control subjects instructed to relax, were compared with respect to degree of relaxation reached as measured by changes in heart rate, tension of the frontalis muscle, and occipital alpha production. The only significant changes were decreases in these measures over time in the control subjects. The changes in the controls were probably the consequence of sleep or the onset of sleep.


[Use of rare earth elements as markers for the study of biologically active compounds. V. Luminescence spectra and binding centers of europium in proteins].

Luminescence spectra of europium ions bound to some proteins are investigated. Europium is shown to coordinate no more than two charged groups, first of all carboxyles. The possibility of more specific coordination of rare earths in proteins is discussed.


[Physical state of crystalline proteins. IV. Melting of trypsin and pepsin crystals].

The nature of heat transitions in trypsin and pepsin crystals during their heating at various rates is studied. Heating is shown to bring about only the denaturation of protein molecules in crystals.


[Effect of yeast cell membrane components on the IR spectrum of the cell].

IR-technique was used to study the effect of yeast cells treatment by water-alcohols mixtures on the quantitative relationship between the intensities of different bands in the spectra. The analysis of spectra made it possible to suggest that the reflection of the IR-irradiation from the cell is governed by the nucleoprotein layer of its envelope. It is shown that the treatment of yeast cell with ribonuclease raises the "IR-permeability" of the cell envelope.


[Spectroscopic study of conformational changes in proteins in aqueous solutions and mixed solvents].

The character of temperature changes of the absorption spectrum of water in protein solutions is the evidence of conformational changes of protein macromolecules. Along with the denaturation processes changes are also clearly seen at predenaturation stage. These changes involve a break of hydrophobic bonds in protein molecules and subsequent exponing of non-polar radicals into water. Thermodynamic characteristics of conformational changes of some proteins in aqueous solutions and water-organic mixtures are determined.


Allograft nephrectomy.

The indications, complications and results of 54 allograft nephrectomies undertaken in 44 patients have been reviewed. There were 7 deaths following 39 nephrectomies done within 6 months of transplantation and complications occurred in a further 14 instances. Many of these resulted from pre-existing infection. When nephrectomy was carried out 6 months after transplantation there were no deaths and morbidity was less. If graft failure is diagnosed within 6 months of transplantation immediate nephrectomy is recommended to prevent future complications. When graft failure occurs later it is suggested that nephrectomy be undertaken only when definite indications for this are present.


The value of prophylactic antibiotics in transurethral prostatic resection: a controlled trial, with observations on the origin of postoperative infection.

Prophylactic antibiotics significantly decrease the incidence of urinary tract infection following endoscopic prostate resection. They are ineffective in reducing the incidence of postoperative fevers, or in reducing the frequency of positive blood cultures during or after operation. A majority of prostate glands harbour colonies of potentially pathogenic organisms, and these are the commonest source of infection of the urinary tract following release by prostatic surgery.


Limited intertransverse fusion using iliac grafts.

Fusion of the lower lumbar spine or lumbosacral joint can be achieved by the use of limited intertransverse iliac grats inserted by a lateral approach. The method offers certain special advantages and is no less successful than other techniques in common use.


Prophylactic lincomycin in the prevention of wound infection following appendicectomy: a double blind study.

The prophylactic use of a single dose of lincomycin in 100 patients undergoing appendicectomy reduced the incidence of postoperative wound infection from 17 to 6 per cent compared with a similar group of control patients. There was no correlation with the histological finding in the appendix, but patients with perforated appendicitis were excluded from the study. Bacteriological examination of the appendix area before surgery showed that Bacteroides fragilis and Escherichia coli were the organisms most frequently isolated. The majority of wound infections were due to B. fragilis, either alone or in association with aerobic organisms, but infection due to E. coli and Staphylococcus aureus also occurred. Systemic antibiotic therapy can successfully reduce the complications following appendicectomy but it is necessary to use a compound with activity against anaerobic organisms.