The binding of diiodosalicylate and flufenamate to the plasma antiactivator: analysis of chemical fibrinolysis.

The fibrinolytic effect of diiodosalicylate was expressed as apparent units urokinase. The dissociation constant of the urokinase-inhibitor complex is increased 19 times in the presence of 10(-2) M diiodosalicylate. The binding of diiodosalicylate to the antiactivator was estimated and the increase in free urokinase in the presence of diiodosalicylate was calculated. With 10(-2) M diiodosalicylate present only 4% of the inhibitor remains free to bind urokinase. Therefore, the fibrinolytic action of diiodosalicylate can be explained on the basis of its binding to the inhibitor and the release of free urokinase.


Cyclic changes in the surface structure of the cervix from the ewe as revealed by scanning electron microscopy.

Thirty parous ewes were divided into six groups and sacrificed on day 0 (first day of estrus), 1, 2, 10, 15 or 16 of the estrous cycle. The cervices were removed immediately and processed for examination with the scanning electron microscope. Observation of the tissues reveals that the surface of the cervix is highly convoluted, which results in the formation of numerous folds or crypts. Two forms of columnar epithelial cells, a ciliated and a non-ciliated cell with microvilli, line the luminal surface of the cerix in the day 10, luteal-phase ewes. However, on day 15, 2 days before estrus, the non-ciliated cells differentiate into two morphologically distinct types of secretory cells. One type forms when the apex of the non-ciliated cell dilates outward into the lumen of the cervix. Concurrent with apical enlargement, the microvilli are lost and the limiting cell membrane becomes smooth. The other type of cell is characterized by only a slight apical swelling. Consequently, remnants of microvilli along with secretory granules can be observed on the limiting membrane of this cell. Both cells release a particulate component, which is believed to be a precursor of mucus, into the lumen of the cerix. These particles undergo a series of morphological transformations to form a fibrillar layer, generally referred to as 'cervical mucus', that covers the epithelial surface at estrus. One to 2 days following the onset of estrus, the fibers become more closely assoicated with amorphous material that begins to coagulate, thereby revealing the underlying ciliated and non-ciliated cells that characterize the cervix of the luteal-phage ewe. The cyclical variation in secretory cells and factors that may influence that structural transformations which occur in mucus are discussed.


Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat.

Sodium fluorescein (10%) when injected intravenously (5 ml/kg) in pregnant albino rats crossed the placental barrier and appeared to be distributed throughout the fetus within 15 min. It was detectable in the fetus up to 4 h after injection but not beyond 24 h. A single intravenous administration of sodium fluorescein did not produce embryotoxic or teratogenic effects. Oral LD50 studies using sodium phenobarbital on rats which received sodium fluorescein during their fetal development showed no apparent effects of sodium fluorescein on their drug detoxification systems.


Partial death as a defining characteristic of a subculture.

This paper presents a discussion of the idea of "partial death" as it relates to the subculture of the beats or hypsters, especially in San Francisco, from about 1948 to 1964, with special emphasis on the works of Kerouac and Ginsberg and a study by Rigney and Smith.


Attenuation of ultrasound in skeletal muscle.

Ultrasonic attenuation in fresh and 5% formalin fixed beef skeletal muscle has been measured, as a continuous function of frequency, in the range 1-8 MHz, for muscle fibre orientations both parallel and normal to the direction of propagation. Good agreement was found in all cases between two independent sets of measurements employing transmission and reflection techniques respectively. The data are consistent with a power law dependence of attenuation coefficient on frequency, with an exponent that is not significantly different from unity. For propagation normal to the fibres attenuation values are found as 1.1 +/- 0.15 and 1.6 +/- 0.15 dB cm-1 MHz-1 for fresh and fixed tissue respectively, the corresponding values for parallel propagation being 2.9 +/- 0.23 and 4.1 +/- 0.25 dB cm-1 MHz-1.


Prolactin, LH, TSH, T3 and T4 in patients with urogenital carcinomas.

Serum level of peptide hormones LH, FSH, TSH and prolactin have been measured in patients with urogenital tumor. In this randomized study we found a frequent elevation of TSH and prolactin, which did not correlate. Increased serum level of TSH was confirmed to be without any elevation of serum T3 and T4. In some of these patients ectopic production of peptides may account for this abnormality. Systemic change of peptides in elderly patients, however, must be taken into consideration as well.


Intravesical formalin for the control of intractable bladder haemorrhage secondary to radiation cystitis or bladder cancer.

During the last two years, 17 patients with haemorrhage due to radiation cystitis or bladder cancer have been treated by intravesical infusion of 10% Formalin solution. The results were very good in 9 cases, satisfactory in 3, while the remaining 5 cases were disappointing. The control of bleeding by Formalin was safe especially in patients with secondary haemorrhage due to radiation cystitis with no tumour recurrence.


[Heat development during tur. experiments with thermoelectric urethra model (author's transl)].

With the help of a new urethra phantom temperatures caused by leak currents during TUR have been measured. Quantitative analysis indicates the demand for maximum output power of 120 W during TUR.


Why Marshall-Marchetti operation works . . . or does not.

Vesicourethral suspension operations fail (1) when preoperative evaluation is insuffcient, leading to improper selection of patients; and (2) for technical reasons when anatomy is uncorrected (suture malplacement, suture breakage, and failure to release adhesions) or when anatomy is corrected (periurethral fibrosis, fistula, stone or granuloma formation on nonabsorbable suture, and overcorrection). Vesicourethral suspension operations work by changing urethrotrigonal anatomy, creating a new equilibrium of forces acting on the bladder neck and urethra.


Niemann-Pick disease in a poodle dog.

A 5-month-old minature Poodle dog had widespread cytoplasmic vacuolation of neurons in the central nervous system and foamy macrophages in the lung, spleen, renal lymph node, liver, adrenal gland and intestine. Concentric membranous cytoplasmic inclusions were seen in the neurons of the central nervous system by electron microscopy. There was no sphingomyelinase in the brain tissue. Sphingomyelin and cholesterol were increased in brain, kidney and liver. A diagnosis of Niemann-Pick Disease was based on absence of sphingomyelinase activity, as well as on histologic, histochemical and chemical findings.


Impotence in the bull: (1) Abnormal venous drainage of the corpus cavernosum penis.

Six young bulls (two Friesian, two Charolais, one polled Devon and one North Devon) that had never served successfully, showed good libido but lacked penile erection. In five of these bulls, the short flaccid organ was not protruded during attempted service. Radiography of the cavernous bodies and veins of the penis in the living animal demonstrated major venous drainage of the corpus cavernosum penis (ccp) by the dorsal venous system in all cases. This was not seen in normal bulls. Radiography and anatomical preparations of post mortem specimens showed that the ccp was drained by the dorsal venous system throughout the length of the organ. Proximally, the cavernous spaces of the ccp anastomosed with those of the corpus spongiosum penis (csp) and were drained by numerous small veins. Distally, a system of larger veins, not seen in normal bulls, drained into left and right sides of the dorsal venous system. No microscopical abnormalities of spermatozoa or of testes were found, but there was a marked lack of spermatozoa in the caudae epididymides. The evidence suggests that abnormal venous drainage of the ccp may have been the immediate cause of impotence in these bulls.


A study of the effects of copper deficiency in Scottish blackface lambs on improved hill pasture.

One member of each pair of twin lambs from 37 five-and six-year-old Scottish blackface ewes, grazing reseeded pasture suspected of causing a molybdenum-sulphur induced copper deficiency in sheep, was given an injection of 12.5 mg copper calcium edetate at about eight weeks of age. Plasma copper concentrations of these lambs were maintained in the normal range by further injections of copper as required (treatment group). The remaining member of each twin pair received no copper therapy (control group). The control lambs and all ewes showed marked hypocupraemia throughout lactation, whereas the plasma copper concentrations of the treatment lambs, and also of single lambs with continuous access to unimproved hill grazings, remained normal. The live-weight gain of the treatment lambs was significantly greater than that of the control lambs, the difference in mean live-weights after 12 weeks being 2.5 kg. All lambs showed some degree of osteoporosis; this was most severe in the control lambs which had less dense bones and were also more susceptible to bone fractures and to disease. Differences between treatment and control lambs were also observed in haematological parameters and in fleece characteristics.


[Experimental gluing of the pleural cavity].

In experimental research on rabbits the authors assessed the usefulness of tissue adhesive-GRF in obtaining tissue union in the pleural cavity to replace aspiration drainage after thoracosurgical operations. The experiments were carried out on rabbits under general anaesthesia in two groups. First group had thoracotomy and after expansion of the lungs the chest was closed tightly. In second group after thoracotomy the lungs were stabilized with gelatin-resorcin-formaldehyde glue. Aspiration drainage was not used. The observation included: radiologic examination, measurements of pulmonary ventilation using Wright's volumometer and gasometric determination. Moreover the alveolar-capillary oxygen difference and the percent of lung shunt were determined. The authors underline good function glued lungs.


Mechanisms of hypogonadism and feminization in alcholic liver disease.

Based upon studies in man and animals it is proposed that: 1. Alcohol-induced hypogonadism is primarily due to a direct testicular toxicity of ethanol manifested by alcohol-induced reduced testosterone levels. 2. In addition, an alcohol-induced central defect also may contribute to the observed hypogonadism. 3. In contrast to the ease with which hypogonadism can be ascribed to androgen deficiency per se, the observed feminization can not be ascribed to altered estrogen levels alone. Rather, we would propose, that feminization of such men is due to the combined effects of estrogen excess and androgen deficiency upon the patter of estrogen-binding proteins in hepatic cytosol.


[Survival of Cochliobolus miyabeanus in the soil (author's transl)].

Survival of C. miyabeanus in irrigated soils of rice fields was higher in infected rice straw (70 days) than in infected rice leaves (40 days). The fungus survived longer in soil depth of 30 cm as in a depth of 15 cm. Between the survival of the fungus and the destruction of infected plant material exist a correlation. In infected rice seeds survived the fungus longer by 5--8 degrees C than by 26--33 degrees C.


[Role of genetic factors in the formation of trace reactions in man].

Trace processes due to presentation of visual nonverbal information, and the dynamics of the bioelectrical parameter (mean level of asymmetry of EEG-waves) were studies in 32 pairs of monozygote and 38 pairs of dizygote twins with twins method. Statistical processing of the data revealed a significant effect of genetic factors on the formation of individual variability of the characteristics of trace processes in humans. The results obtained showed that with increased functional load the intrapair similarity of trace reactions increased in monozygote twins and did not change or decrease in dizygote twins and in unrelated pairs. This fact is interpreted at a dependence of appearance of geneticly determined neurophysiological characteristics on the level of functional activity of the nervous system.


Amino acid content in relation to growth of Helminthosporium maydis Nishikado and Miyake.

During the growth period of thirty days, altogether thirteen amino acids showed their presence and activity in the developing culture of Helminthosporium maydis Nishikado and Miyake. Initiation of growth by the 5th day coincided with the appearance of profuse amounts of dl-alanine and serine, and moderate amounts of valine, threonine, and aspartic acid. The thirteen amino acids, which appeared in full complement by the 15th day, were actively engaged in accelerating mycelial accumulation. Beyond this growth period, there was a decline in the amino acids.


Varying spectrum of amino acids in relation to growth in Helminthosporium oryzae Breda de Haan.

Fifteen amino acids were detected in the developing mycelium of Helminthosporium oryzae Breda de Haan. During the first fortnight of mat accumulation, which was more rapid, a marked influence of amino acids on the growth pattern was discernible. A high level maintenance of dl-alanine l-cysteine, l-leucine/isoleucine, threonine, tyrosine, glutamic, and aspartic acids, as well as an increase in the amount of gamma-aminobutyric acid and proline during the first fortnight of culture development were effective in initiating growth and keeping it at a more rapid pace. Glutamine and methionine appeared in the latter half of fungal growth. During this slow pace of mycelial accumulation in the latter half period, there was a general and overall decline in the amount of most of the amino acids. The amino acids started disappearing from the mycelial extract from the 20th day onwards till the end of the 30th day. In the culture filtrate, aspartic acid and proline appeared during the rapid growth phase and dl-alanine and methionine during the slower phase.


Fluctuation in amino-acid constituents of a developing culture of Sclerotium rolfsii Sacc. and its relation to growth.

Altogether eleven amino acids were detected in the mycelial extract of Sclerotium rolfsii Sacc. Here, with the appearance of aspartic acid and homoserine on the 5th day, growth was initiated. The maximum mycelial output, achieved by the 15th day, coincided with the detection of leucine/isoleucine and valine in the mycelial extract and of methionine in the culture filtrate. Lysine and gamma-amino-butyric acid which appeared late in the mycelium did not contribute to its growth. Tyrosine, an aromatic amino acid, was present only in the culture filtrate and not in the fungal extract. Aspartic acid, homoserine, and methionine were profusely produced in the culture filtrate during the decline of mycelial growth, suggesting that these amino acids could be fungal autolysis products as well.


[Studies on habitat of fungi on glass fibre wallpaper (author's transl)].

The fungi strains Alternaria tenuis C.G. Ness and Ulocladium alternariae (Cke.) Simmons could be isolated from black coloured glass fibre wallpaper. It was investigated that glass fibre wallpaper and covering pastes were not substrate medium but were settled by fungi when there were nutrition substances under or in the air volume of the wallpaper. Both isolated fungi strains converted carboxymethyl-cellulose as alone C- and energy source. The fungicide Smotilon AM limited the spore germination growth of both strains with 0.5% solution. The formation of the biotop glass fibre wallpaper for fungi was discussed.


[The effect of local heat and cold packs on the skin temperature at the knee joint].

Using the infrared radiometer KT 41, skin temperature of the knee joint was measured in 5 healthy persons on five different points. With the same method skin temperature of knee joints was estimated after hot mud packs of 20 minutes duration and cold packs with frozen bags of 30 minutes duration. The highest temperatures were estimated near the popliteal space, the lowest temperatures on the patella. During 24 hours, a distinct periodical course of skin temperature could be observed. After the hot pack skin temperature of the treated joint significantly rose; after 1 hour the average temperature before heat application was reached again. After cold application with deeply frozen bags, skin temperature dropped drastically and remained colder than pretreatment temperature for almost 5 hours. Heat application did not influence skin temperature of untreated contralateral knee but during cold application also the temperature of untreated knee slightly decreased. Considering the correlation between skin temperature and intraarticular temperature of joints, the effect of local heating and cooling seems to be more intense than supposed and confirms the therapeutic benefit of heat and cold in rheumatology.


Investigation of effect of alpha-naphthylamine and beta-naphthylamine on organic acids formation of self-sustaining coacervates.

Malonic and oleic acids were found in the typical mixtures. Samples containing alpha-naphthylamine gave oleic and malic acids which disintegrated with time of exposure. Tricarballylic acid was confirmed in presence of beta-naphthyl amine, but disappeared with time. Arachidic, tartaric, and adipic acids were found, but they disappeared in eight days' exposed samples. At later stages of exposure, malonic acid was observed along with sporadic appearances of citric , succinic, and oleic acids. Rate of disintegration of these compounds was directly proportional to time of exposure to sunlight.


[Immunogenic and adjuvant properties of rat erythrocytes subjected to exposure to a high external temperature].

The erythrocytes of Wistar rats, subjected to heating at 40 degrees C (4 times, each heating lasting 40 min.) were found to be more immunogenic in mice than the erythrocytes of intact rats. The immunization of intact Wistar rats, in a single injection, with syngeneic erythrocytes obtained from the heated animals did not induce immunological response reaction, whereas 5 injections of these erythrocytes caused an increase in the number of rosette-forming cells. The injection of syngeneic erythrocytes obtained from the heated rats to intact animals also stimulated the development of immune response to sheep erythrocytes.


Light-induced rhythms of prolactin secretion in the ram and the effect of cranial sympathectomy.

Four Soay rams cranially sympathectomised by removal of the superior cervical ganglia were housed alongside 4 control rams in an artificial lighting regime of alternating 16 week periods of short days (8L : 16D) and long days (16L : 8D) for 2 years. The variations in the plasma prolactin concentration revealed that while the control animals adjusted both the short term (diurnal) and long term (seasonal) rhythms in prolactin secretion in response to the changes in daylength, the ganglionectomised rams failed to respond. These sympathectomised animals continued to show long term changes in the circulating level of prolactin however and during the periods of hypersecretion a conspicuous diurnal rhythm in the hormone concentration was apparent.


[Effect of destruction of the frontal and parietal regions of the neocortex on the ability of dogs to solve extrapolation problems].

Parietoectomized dogs (n = 8), like intact ones (n = 102), are able to extrapolate the direction of the movement of an alimentary stimulus when presented with a complex task variant. In this they differ from animals with a prefrontal lobectomy (n = 10) in which, according to the authors' previous data (1971), the ability to elementary rational activity in Krushinsky extrapolation test (1977), is impaired.


[Raised serum PRL and androgen levels associated with hyrsutism, amenorrhoea and galactorrhoea].

This is a report of a case of a case of amenorrhoea-galactorrhoea syndrome with hyperprolactinaemia associated with increase of plasma androstenedione and urinary 17-ketosteroids, gradually developed in a sterile subject. Plasma LH and testosterone levels and the results of adrenal suppression and ovarian stimulation tests seem to prove, point towards, the adrenal as the likely source of androgens. Treatment with bromocryptin for 20 weeks brought about a reduction to normal of both PRL and androgens. Resumption of ovulatory cycles followed thereafter and a pregnancy eventually occurred.


Failure of bromocriptine to suppress prolactin in majeptil-induced hyperprolactinemia.

A case of hyperprolactinemic anovulation with amenorrhea and galactorrhea, due to Phenothizine derivative (Majeptil) is presented. Treatment with bromocriptine, 2.5 mg b.i.d., p.o., or L-Dopa, 500 mg, p.o., did not suppress serum prolactin and menstrual cycle was not resumed. Pituitary prolactin response to TRH and Pituitary LH and FSH response to LHRH were found to be normal. It seems that at the dose used, bromocriptine (a dopaminergic agonist) cannot counteract the phenothiazine induced hyperprolactinemia. Hence, it is not effective in induction of ovulation while the patient is under phenothiazine treatment.


Barriers and transport properties of the perineurium. An ultrastructural study with 125I-labeled albuminin and horseradish peroxidase in normal and protein-deprived rats.

The permeability properties of the perineurium in sciatic nerves of 12-week-old rats were studied. The penetration of 125I-labeled albumin and horseradish peroxidase into the perineurium was investigated electronmicroscopically 10, 30, and 120 min after the local extraneural application of the tracers. The autoradiographic study included age-matched protein-deprived rats. It was concluded that the perineurium acted as a diffusion barrier but also permitted a slow passage of the macromolecules into the endoneurium. The result indicates that this penetration to some extent is due to vesicular transport across the perineurial cells. The significance of these barrier and transport properties of the perineurium is discussed. No obvious differences in perineurial permeability between normal and protein-deprived rats were obtained.


Astrocytes in hemangioblastomas of the central nervous system and their relationship to stromal cells.

Thirteen cases of CNS hemangioblastoma were examined with the immunoperoxidase technique for glial fibrillary acidic protein (GFAP) to determine if there were astrocytic elements among the "stromal cells" of these tumors. In six cases, includinng two leptomeningeal hemangioblastomas, none of the stromal cells were positive on GFAP stain. Seven cases, however, showed variable presence of Gfap positive cells, including clusters of heavily lipidized cells deep within cerebellar hemangioblastomas. These GFAP positive cells were indestinguishable by other stains from interstitial or stromal cells. Thus, it appears that in at least some hemangioblastomas of the CNS parenchyma, a few or many "stromal cells" are lipidized astrocytes. All stromal cells, however, cannot be of astrocytic origin, as proposed by Jakobiec et al. (1976), in view of our six cases where no GFAP-positive cells were found in the tumors. It is suggested that cells identified as "stromal cells" of hemangioblastomas on light microscopy are a heterogeneous group of cells including astroyctic as well as other elements and that they resemble each other on ordinary stains because of the "equalizing effect" of cell lipidization.


Ultrastructural studies on the sporulation of oocysts of Toxoplasma gondii. I. Development of the zygote and formation of the sporoblasts.

The initial stages of sporulation in oocysts of Toxoplasma gondii were examined in samples sporulated at 27 degrees C for 0, 6, 12, 16 and 24 hours. The initial zygote was roughly spherical and was limited by a single unit membrane. A few micropores of the inactive type were present on this membrane. The cytoplasm contained a large nucleus with a nucleolus, a number of polysaccharide granules, lipid globules, mitochondria, and Golgi bodies together with a few strands of rough endoplasmic reticulum. After the initiation of sporulation little change was noted in the cytoplasm except for an increase in protein synthesis as evidenced by the augmentation of the amount of rough endoplasmic reticulum and the appearance of polyribosomes. Nuclear division occurred twice giving rise to four nuclei which were situated close to the cell periphery and well separated from each other. At this multinucleate stage a second limiting membrane was formed. The cytoplasmic mass then divided to form the two sporoblasts. This was accomplished by an invagination of the limiting membranes in combination with internally formed membranes. The two binuclear sporoblasts were roughly spherical. They were limited by two unit membranes and contained the same cytoplasmic organelles as described for the zygote.


Ultrastructural studies on the sporulation of oocysts of Toxoplasma gondii. II. Formation of the sporocyst and structure of the sporocyst wall.

The ultrastructural changes observed during sporocyst formation and the structure of the sporocyst wall was examined in oocysts which had been allowed to sporulate for between 12 and 48 hours at 27 degrees C. As the spherical sporoblast developed into the sporocyst the cytoplasmic mass became ellipsoidal in shape although no change was noted in the organelle compliment, which cosisted of two nuclei plus a number of polysaccharide granules, lipid globules, mitochondria, Golgi bodies, and some rough endoplasmic reticulum. The sporocyst wall consisted of a thin outer layer (15-20 nm) which was formed from two limiting membranes of the sporoblast and an inner layer (40-50 nm) which was comprised of four curved plates. This inner layer was formed under the outer layer and, although no specific cytoplasmic organelle disappeared with its formation, some unit membranes were observed close to the plasmalemma during its formation. Each curved plate has a marginal swelling and an interposing strip of material is present between the margins of adjacent plates. The plates are joined to the interposing strip by a thin band of osmiophilic material. In oblique and tangential sections through the plates two types of cross banding were observed which differed in periodicity.


Mechanism of action of the spasmogenic activity of penthylenetetrazol and of 1,2,3,4-tetrahydroisoquinolines on rat stomach fundus strips.

Spasmogenic activity of penthylenetetrazol (PTZ) and 1,2,3,4-tetrahydro-isochinoline (THI) derivatives was gradually reduced during storage of their solutions as tested on rat isolated stomach fundus strips. Spasmogenic activity of both PTZ and THI derivatives could be modified by prior exposure of the solutions to electrostatic field and to rotating magnetic field or ultrasound treatment. As a consequence of rotating magnetic field treatment, ED50 values for 1-phenyl-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinoline-hydrochloride (S-23), PTZ and for PTZ crystallized from an ether solution of PTZ (PTZA) doubled, i.e. their activity was reduced by 50 per cent. After an exposure to rotating magnetic field, intrinsic activity of S-23 fell only by 10 to 20 per cent, while after the same treatment the fall in intrinsic activity of PTZ was more pronounced (40 to 50 per cent). Activity of PTZA changed similarly as that of PTZ. Activity of S-23 was similarly modified by exposure of its solution to electrostatic or rotating magnetic field. On the other hand, intrinsic activity of PTZ solution exposed to electrostatic field was twice as high as that of the control PTZ solution. Affinity and intrinsic activity of PTZ solutions diminished after ultrasound treatment. The fall in the activity of PTZ solution of low concentration was greater after the same ultrasound treatment, but its convulsive activity measured in vivo remained unchanged. Spasmogenic activity of ultrasound-treated PTZ reappeared after the solution had been dried under vacuum and then the residue crystallized and redissolved in water. These findings allow the conclusion that the observed changes in activity could be the result of spontaneous or field-evoked alterations in molecular state (orientation, association etc.) conformation. The fact that the activity of PTZ solution measured in vivo did not change during storage supports this assumption.


Plasma progesterone, oestradiol 17 beta and premenstrual symptoms.

Thirty-nine healthy women, mainly hospital employees, median age 23, kept a daily record of symptoms throughout their menstrual cycles and plasma progesterone and oestradiol 17 beta levels were measured daily in the premenstrual week and second daily for the remainder of the cycle. Groups with symptom scores (affective, somatic and total) above and below the median score were compared with respect to mean plasma hormone levels and the pattern of change of plasma hormones over the 3 weeks before menstruation and the last 7 premenstrual days. Progesterone/oestrogen ratios for the latter period were also compared in the same subjects. No significant differences were found. There was a positive correlation of age with mean plasma progesterone level in the 3 weeks before menstruation.


The timing of menstruation-related symptoms assessed by a daily symptom rating scale.

A daily symptom rating scale (DSRS) was constructed from items previously used in questionnaires and rating scales measuring menstrual symptoms. The DSRS was found to have adequate reliability and validity. The profiles of symptom intensity of 65 women, mainly hospital staff, median age 19, during one menstrual cycle, with particular emphasis on the premenstrual week and menstruation are reported. Significant differences in ratings during the cycle were found. Ratings increased during the premenstrual week and were maximal on the days immediately preceding and following the onset of menstruation. No abrupt decline in ratings was found when menstruation commenced. Results were compared with answers to a menstrual distress questionnaire, previously administered to the same women and the questionnaire results were in good agreement with DSRS results on the day of maximum symptom intensity (the day immediately before or the day immediately after the onset of menstruation.


Steroid hormone regulations of uterine peroxidase activity.

Uterine peroxidase enzyme activity has been studied as a marker for estrogen action in the uterus to help clarify the mechanism of estrogen action and its modulation by antiestrogens and progestins. Estrogen-induced increases in peroxidase were found to closely parallel increases in uterine weight and DNA content in the castrate rat. In the cycling female rat, uterine peroxidase levels were highest during proestrus and estrus and the lower levels of metestrous and diestrous uteri could be raised to estrous levels by administration of estrogen. However, the estrous levels were not further increased by estrogen treatment. The antiestrogen, CI628, while a very weak inducer of uterine peroxidase, is an effective antagonist of the estrogen induction of the enzyme. The prolonged duration of this CI628-effected inhibition corresponds to the prolonged depletion of cytoplasmic estrogen receptor seen with CI628 treatment. Progesterone, R5020 and norethindrone were also found to be effective antagonists of estrogen-induced uterine peroxidase. Medrogestone and clogestrone, less potent progestins in the rat, were also less effective antagonists of peroxidase induction. Since progesterone was found to inhibit peroxidase induction due to both estrone and diethylstilbestrol, as well as estradiol, it is considered unlikely that this antagonism relates to progestin-induced increases in uterine 17 beta-hydroxysteroid dehydrogenase. Rather, it is proposed that progestins, acting through progestin  receptor, may have a more direct role, possibly acting at the level of the genome to repress the expression of estrogen-induced products.


Studies on the incorporation of the sodium channel of lobster nerve into soybean liposomes.

Na+ channels of lobster nerve membrane were incorporated into soybean liposomes by the freeze-thaw-sonication procedure. Electron microscopy showed that the vesicular pattern of membranes and liposomes was broken and reassembled during the process. The amount of membrane protein incorporated depended linearly on the amount of membrane protein added to the liposomes for reconstitution. The 22Na flux into the reconstituted vesicles was increased by veratridine (0.5 mM) or grayanotoxin I (150 microM) and the increment was abolished by tetrodotoxin (Ki = 4 to 5 nM). The drug-sensitive 22Na influx depended linearly on the amount of membrane protein incorporated. No response to the drugs was found in protein-free vesicles or in vesicles reconstituted with membrane heated at 50 degrees C for 15 min. A fraction of digitonin-treated membranes had a higher Na+ channel activity. The Na+ channel was able to discriminate between Na+ and K+ or Rb+.


Common problems in the medical care of pilots.

Family physicians need to have an increased awareness of the medical needs of pilots. A close, trusting relationship is essential. Special consideration must be given when prescribing medications. Hypoxia is a special problem for pilots with cardiovascular and/or respiratory diseases. Several medical problems may occur because of rapid changes in barometric pressure, including barotitis media, which is best treated in flight. Minor ailments, use of alcohol and smoking may become serious problems for aviators; therefore, patient education is important.


Mural vegetations at the site of endocardial trauma in infective endocarditis complicating idiopathic hypertrophic subaortic stenosis.

In two patients infective endocarditis developed as the primary manifestation of idiopathic hypertrophic subaortic stenosis. Infected vegetations were present on the mitral and aortic valves. In addition, bacterial vegetations were observed on the septal endocardium at the site of contact between the mitral valve leaflet and the hypertrophic septum. Thus, chronic endocardial trauma, a common finding in idiopathic hypertrophic subaortic stenosis, may provide a fertile nidus for the development of bacterial vegetation.


The structure and distribution of the cross-striated fibril and associated membranes in guinea pig photoreceptors.

Examination of longitudinally and transversely sectioned photoreceptor cells of the guinea pig retina revealed an aggregate of thin filaments forming a single cross-striated fibril coursing through the full length of the non-receptor portion of the cell. The fibril begins as the ciliary rootlet from the region of the basal body of the connecting cilium. From the basal body it passes between the mitochondria of the ellipsoid and along the Golgi zone of the myoid region of the inner segment, narrowing from an irregularly shaped bundle to a ribbon-shaped aggregate. The fibril separates into discrete strands, each curving along the nucleus, reuniting into a single bundle to pass down the cell's axon, and terminating deep within the synaptic terminal. The fibril is flanked by two separate membranous saccules, each continuous along nearly its full length. The fibril's extensive course in the guinea pig and its association with continuous membranes necessitates a reexamination of earlier proposals for the function of cross-striated filamentous structures in photoreceptor cells.


Diurnal variations in plasma concentrations of tryptophan, tryosine, and other neutral amino acids: effect of dietary protein intake.

The effect of dietary protein content on the diurnal variations in plasma neutral amino acid levels was studied in normal human subjects. For three consecutive 5-day periods, subjects consumed diets containing 0, 75, or 150 g of egg protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each period. Consumption of the protein-free diet caused plasma concentrations of all amino acids studied to fall in the late morning and afternoon, while the 150-g protein diet elicited increases in these levels during the daytime. Ingestion of the diet containing 75 g of egg protein tended to diminish the amplitudes of the daily rhythms in plasma amino acid levels, but most amino acids still exhibited small but significant elevations late in the evening. At all times of day, plasma concentrations of the large neutral amino acids studied (i.e., aromatic and branched-chain amino acids, and methionine) varied directly with the protein content of the diet. In contrast, the relationships between dietary protein content and the plasma concentrations of glycine and alanine, two small neutral amino acids, were inverse. The ratios of plasma tryptophan, tyrosine, and phenylalanine levels to the sum of the concentrations of other large neutral amino acids tended to fall as the protein content of the diet was increased. The corresponding ratio for valine increased as protein was added to the diet, while the leucine and isoleucine ratios were not correlated with dietary protein content. Since diet-induced changes in plasma trypotphan and tyrosine ratios in animals are known to cause parallel alterations in brain tryptophan and tyrosine levels, and thus in the rates of brain serotonin and catecholamine synthesis, our data suggest that ingestion of carbohydrates and protein may also normally affected brain monoamine synthesis in humans.


Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.

The effect of varying dietary protein content on the daily rhythms in plasma neutral amino acid concentrations was studied in patients with chronic cirrhosis. For two consecutive 5-day periods, subjects consumed diets containing either 0 or 75 g of protein per day. Blood samples were drawn at 4-hr intervals on the 4th and 5th days of each dietary period. For most of the neutral amino acids, the changes in plasma concentration associated with time of day or with variations in dietary protein content were similar to those observed previously in normal subjects. Ingestion of the protein-free diet caused significant reductions in the daytime level of all amino acids studied, except for tryptophan, the concentration of which did not change during the 24-hr period. Ingestion of the 75-g protein diet caused plasma levels of most of theamino acids to increase slightly during the day; these increments were not statistically significant for tryptophan, tyrosine, leucine, and methionine. The absolute plasma concentrations of most of the neutral amino acids were also in the normal range; exceptions included methonine, tyrosine, and phenylalanine, whose plasma levels were significantly elevated above normal valves. The plasma ratios of tryptophan, tyrosine, and phenylalanine concentrations to the sum of the concentrations of other large neutral amino acids increased during the day uhen the protein-free diet was ingested; this effect was moderated by the addition of protein to the food. The plasma ratios for the branched-chain amino acids were depressed below normal; those for tyrosine, phenylalanine, and methionine were significantly increased. The plasma tryptophan ratio was within the normal range. These findings provide a basis for anticipating that the uptake from blood into brain of several of the large neutral amino acids may be modified in patients with chronic cirrhosis.


Increase of IgA-bearing peripheral blood lymphocytes in families of patients with IgA nephropathy.

IgA-bearing peripheral blood lymphocytes, serum IgA, urinary sediments and HLA types of patients with IgA nephropathy and members of their families were examined to elucidate whether some familial factors might be related to the development of IgA nephropathy. Ten patients with IgA nephropathy, 31 family members and 36 age-matched healthy persons were examined. All families included certain members with increased amounts of IgA-bearing peripheral blood lymphocytes. The pattern of the emergence of family members with increased IgA-bearing lymphocytes was vertical. Some family members who had increased IgA-bearing lymphocytes showed microhematuria at the time of the study. There was no significant correlation between the amounts of IgA-bearing peripheral blood lymphocytes and levels of serum IgA. HLA types of the ten patients did not show significant deviation from those in the general population. It is suggested that the measurement of IgA-bearing peripheral blood lymphocytes among family members is useful for the screening of patients with IgA nephropathy.


Immune thrombocytopenic purpura in Hodgkin disease.

Immune thrombocytopenic purpura is rarely seen in Hodgkin disease and the presence of platelet-associated antibody has not been previously reported in these patients. A patient with Hodgkin disease is described who developed a destructive thrombocytopenia demonstrated by shortened platelet survival. In conjunction with his thrombocytopenia, he had marked elevation of platelet-associated immunoglobulin G levels (nanograms IgG per 10(9) platelets: 15,187 prior to splenectomy and 71,130 and 81,900 after surgery). Mean values (+/-SD) of control subjects averaged 1,975 + 381 and four patients with Hodgkin disease and normal platelet counts had levels ranging from 1,581 to 4,011. We suggest that this patient had immune-mediated thrombocytopenia; whether the increase in platelet-associated immunoglobulin G was due to antiplatelet antibody or to adsorbed or phagocytosed immune complexes cannot be demonstrated by these studies. The platelet-associated immunoglobulin G test may be useful in evaluating these patients.


A syndrome resembling idiopathic thrombocytopenic purpura in 10 patients with diverse forms of cancer.

Ten patients with diverse forms of carcinoma (six patients) and of cancer in the lymphoid system (four patients) presented with or subsequently had a syndrome resembling idiopathic thrombocytopenic purpura (ITP). These patients were older than patients who had ITP alone. ITP was coincident with a diagnosis of cancer (three patients), preceded a diagnosis of cancer (three patients) or followed a diagnosis of cancer (four patients). No patients responded to steroid therapy permanently. Therefore, the course of our patients was fairly typical of ITP in the adult. Since we found nine patients with cancer in a survey of 52 consecutive patients with ITP in the adult population admitted to one hospital, this diagnosis may be missed with some frequency; the development of thrombocytopenia being attributed to other causes.


A dog model for human psychopathology.

The author reviews studies of the development and scientific exploitation of two true-breeding strains of pointer dogs, one of which is basically normal and one of which is nervous, particularly around people. Basic studies, which generally contrast the nervous dogs with the normal dogs, include studies of inheritance, early experience, conditioning, psychophysiology, neuropharmacology, and neurochemistry. The author suggests that the nervous line is an animal model of human psychopathology and probably of cardiac pathology.


Morphologic and functional changes of the aortic intima during experimental hypertension.

The morphology and permeability to horseradish peroxidase of the rat aortic intima have been investigated in three experimental models of hypertension having different values of plasma renin content and plasma aldosterone level. During hypertension the aortic endothelium shows three main changes: 1) increased arithmetic mean thickness, with prominent rough endoplasmic reticulum and polyribosomes; 2) the appearance of actin microfilament bundles; and 3) increased permeability to horseradish peroxidase. These changes are not present in all models, do not appear to depend on hypertension per se, and are independent of each other. The subendothelial layer of hypertensive animals shows an increased thickness that appears to be correlated with an increase of endothelial cell volume. Our results suggest that: 1) the aortic intima reacts differently to different types of hypertension, and 2) factors other than hypertension per se play a role in the development of vascular changes observed in animals with elevated blood pressure.


Occurrence of oocytes in the liver of the percoid fish, Trichogaster fasciatus (Bloch and Schneider) and its probable significance.

Out of 500 Trichogaster fasciatus examined in one fish stage I and II oocytes were noticed in the liver and its blood sinuses. Apparently this is the first record of such occurrence. It is highly suggestive of the vascular migration of the germ cells enroute to the genital ridge. Possibly due to unknown reasons some might have been stuck up in the liver which is highly vascular.


Use of a twelve-hour theophylline preparation in chronic adult asthmatics.

Twenty-one adult chronic asthmatic patients were studied while taking a 12-hour sustained-action theophylline tablet. Pulmonary function testing and serum theophylline levels were monitored for 12 weeks, including testing every two hours over one dosing interval on the final day of the study. Results indicate the preparation tested produced sustained stable theophylline levels for a full 12 hours, with pulmonary function also remaining elevated and stable during this period. There was minimal toxicity reported over the 12-week period and no evidence of tolerance.


Production of labile Newcastle disease virus progeny after infection of chicken embryo cells in the presence of caffeine.

A study was undertaken to examine the effects of caffeine on Newcastle disease virus (NDV) infection of chicken embryo cells. Addition of 10 mM caffeine to the growth medium produced 95% reduction in progeny synthesis, 63% reduction in RNA synthesis, 45% reduction in protein synthesis, and 25% reduction in hemadsorption ability in NDV-infected cultures when compared with untreated, infected cultures. Purified NDV obtained from caffeine-treated, infected cultures was more sensitive to ultraviolet irradiation and to damage by freezing and thawing than was observed in untreated virus cultures. The SDS-polyacrylamide gel electrophoresis revealed that purified virions contained the same complement of polypeptides, but there was a significant variation in the quantities of several of the NDV polypeptides.


Effect of intrauterine saline infusion during the late luteal phase on the estrous cycle and luteal function of the mare.

The intrauterine infusion of 500 ml of warm sterile saline solution into mares on days 12, 13, or 14 after ovulation failed to alter the ovulatory interval, although intervals were shorter for days 12 and 13 (20.6 days) when compared with those in control mares (21.6 days). The IU fusion shortened luteal-life-span on days 12 (12.0 vs 13.8 days) and 13 (13.0 vs 14.4 days) (P is less than 0.05), but not day 14 (14.0 vs 13.5 days), when comparing the effects of IU infusion with an average of before and after base-line data. There was no effect on the interval from corpus luteum regression to ovulation, ie, the final follicular phases. The treatment average for days 12 and 13 combined was 7.7 days vs 7.3 days for controls. Also, no significant effect was observed for the duration of estrus in that the treatment average for days 12 and 13 was 5.1 days, and for controls, 6.0 days. The infusion of saline solution caused an immediate release of prostaglandin F(2alpha) within 5 minutes, with additional large releases occurring over the next 24 hours. Progestin concentrations decreased rapidly in relation to this prostaglandin release.


Critical evaluation of taeniacidal antibiotic S15-1 (SQ 21, 704) for removal of natural tapeworm infections in dogs and cats.

The new taeniacidal antibiotic S15-1 (SQ 21,704) was evaluated against naturally occuring infections of Taenia pisiformis in 53 dogs, Dipylidium caninum in 35 dogs, T taeniaformis in 18 cats, and D caninum in 33 cats. It all instances, the compound was administered in gelatine capsules in a single oral dose. The doses tested were between and 200 mg/kg of body weight in dogs and between 15 and 45 mg/kg in cats. In dogs, doses of 25 mg/kg and greater were 100% effective against T pisiformis, whereas a dose of 50 mg/kg was necessary to clear D caninum. In cats, a single oral dose of 22.5 mg/kg was 100% efficacious against T taeniaeformis, and a single dose of 45 mg/kg (the largest dose tested) clearly seven of eight cats of D caninum. The efficacy was limited to tapeworms only; there was no efficacy against nematodes. The antibiotic was well tolerated by both species with no drug-related vomiting or other side-effects observed.


Taeniacidal efficacy of SQ 21,704 in dogs by various types of oral administration and in comparison with niclosamide and bunamidine hydrochloride.

The streptothrinin antibiotics SQ 21,704 was evaluated against naturally occurring Taenia pisiformis and Dipylidium caninum infections in dogs when they were given at a dose level of 37.5 mg/kg of body weight in four different rations: loaf-type canned meat; chunk-type canned meat; dry (gravy-type) meal; and dry (pelleted) meal. The SQ 21,704 was 100% efficacious against both T pisiformis and D caninum infections when given with the chunk, gravy, and pelleted rations. When given with the loaf-type canned meat, it was 100% effective against T pisiformis and 60% efficacious against D caninum. The SQ 21,704 was effective against both tapeworm species when given orally as a liquid at a dose level of 37.5 mg/kg, formulated as an aqueous suspension containing 94 mg of activity per milliter. The SQ 21,704 was also tested in dogs when given orally in gelatin capsules at a dose level of 37.5 mg/kg without fasting, and was 100% efficacious against both tapeworm species. The results of a comparative taeniacidal study demonstrated that SQ 21,704 was 100% effective in removing both T pisiformis and D caninum when administered orally at a dose level of 37.5 mg/kg, whereas niclosamide and bunamidine hydrochloride were only partially effective at their recommended dose levels. One of five dogs treated with niclosamide at a dose level of 157 mg/kg was positive at necropsy, giving an orally efficacy of 80%. Three of five dogs treated with bunamidine hydrochloride at a dose level of 49 mg/kg were positive at necropsy, giving an overall efficacy of 40%.


Chronic pleural blastomycosis with hyperprolactinemia, galactorrhea, and amenorrhea.

A patient with pleural blastomycosis developed hyperprolactinemia with amenorrhea and galactorrhea. These abnormalities were corrected by treatment with amphotericin B. Chest wall stimulation secondary to the pleural infection might have resulted in these endocrine abnormalities.


The heart and cardiac conduction system in thrombotic thrombocytopenic purpura. A clinicopathologic study of 17 autopsied patients.

The relation between the heart lesions of thrombotic thrombocytopenic purpura and clinical cardiac dysfunction was studied in 17 autopsied patients. Thirteen of the 17 patients had extensive small-vessel thromboses and in some instances hemorrhages and focal necroses within the heart. Congestive heart failure was present in nine of the 17 patients. Thrombotic microcirculatory cardiac lesions and anemia-related high cardiac output may have contributed to cardiac dysfunction. Serial histologic sections of the cardiac conducting system in 10 patients showed microthrombi in seven and associated hemorrhages in five. Lesions were localized to the atrioventricular node and His bundle parts of the system with sparing of the sinoatrial node and bundle branches. Two patients had electrocardiographic evidence suggesting lesions within conducting tissues. Thrombi and hemorrhages are common findings in the conducting tissues in thrombotic thrombocytopenic purpura and may account for cardiac arrest or transient rhythm disturbances.


[New analytic criteria for the characterization of wines].

Isotopic analysis, determination of radioactivity are factors allowing a better characterization of wines. The analysis of the composition in stable isotopes of the constituants of wine can provide new analytic criteria for characterizing wines. Thus, the concentration of 13C in ethanol can allow the disclosure of an addition of cane sugar or maize sugar to the musts. A study of the composition in stable isotopes of the water of wines of a certain region made it possible to show a correlation between the amount of D and 18O in the water of wine, and the alcohlic concentration. The setting up of the curve showing the decrease of the radioactivity of 14C in the Girondewines allows a determination of the date, accurate to within one year, of these wines. The enzymatic determination of the gluconic acid present in the wines produced from crops attacked by Botrytis Cinerea allows one to estimate the type of rottenness of the grape; the gluconic acid, which is only present in very small quantities in wines produced from sound grapes, represents about 50 p. 100 of the fixed acides of the grapes affected by "noble rottenness" and up to 90 p. 100 in the case of adultarated grapes. Thanks to the recults obtained in 1976, standards are proposed to allow the characterization of the wines produced from grapes affected by "noble rottenness", so that they can be distinguished from, on the one hand, the wines produced from sound grapes, and on the other hand, the wines produced from adultarated grapes.


[Excretion of androsterone and etiocholanolone related to plasma testosterone binding in three male pseudohermaphrodites (author's transl)].

The authors studied the relation of plasma testosterone and Sex-Hormone-Binding-Globulin levels to the urinary excretion of androsterone (A) and etiocholanolone (E) in three patients with the syndrome of testicular feminization. They found levels of SHBG in the upper female range, testosterone concentration in the normal male range and urinary excretion rate of A and E in the normal female range.


Failure of deodorized males to induce oestrus in the wild mouse.

The ability of female mice to return to oestrus following exposure to males perfumed either with oil of wintergreen or with the commercial perfume, "Kanta" was evaluated. Unisexual grouping of female mice induced anoestrus in all individuals. Oestrus was, however, promptly induced in the majority of unisexually grouped females by exposure to normal males. By contrast, exposure to perfumed males failed to induce oestrus in unisexually grouped females. The results suggest that male urine which is the source of the primer pheromone involved in the induction of oestrus was ineffective because of the masking effect of artificial scents. Hence the unisexually grouped females were unable to perceive the pheromone from males and continued to remain in anoestrus following exposure to perfumed males. The results provide additional evidence in support of the view that the urinary pheromone produced by males induces oestrus in females by acting through olfactory pathways.


[The Gongylonematid parasitic in the elephant shrew Elephantus rozeti (Macrocelidae) in Tunisia was identified as Gongylonema brevispiculum Seurat, 1914 (author's transl)].

Its larval form obtained from experimentally infected intermediate hosts, differs from those of other Gongylonematids. In the genus Gongylonema four types of larvae were recognized. They are characterized by the size and the cephalic and caudal structures of the larvae. The cellular reactions caused by the larvae of G. brevispiculum in the insect muscles are similar to those caused by infections with larvae of Acuarid nematodes.


[Microfilaricidal action of Diethylcarbamazine on Dipetalonema dessetae in his natural host (author's transl)].

With a Filaria of Rodent whose microfilariae are periodic and diurnal, and destroyed by DEC, the authors don't observe the immediate rise of microfilaria count sometimes noted following treatment of periodic filaria during the low phase of microfilaremia. Moreover, the microfilaremia falls at 30% of the pre-treatment level after 15 mn. This may be in relation with the swift digestive absorption, as detected by the rise of the DEC serum level, whose maximum is reached within 15 mn.


Anencephaly in Japan: paternal age, maternal age and birth order.

The statistical association between incidence of anencephaly and paternal age, maternal age and birth order was analysed in 1815 cases of foetal deaths with anencephaly reported during 1975--6. The birth order association was confirmed with an extremely high degree of statistical significance.


On the use of multiple thresholds for the determination of the mode of inheritance of semi-continuous traits.

In this article we reconsider the analysis proposed by Reich et al. (1972) for determining the mode of inheritance for semi-continuous traits from intrafamilial data. We consider both the (general) multifactorial and the single-locus model formulation. We show (numerically), by using a much improved numerical analysis technique for the parameter estimation, that there may be many single-locus models that could have given rise to a particular data set, dependent on its size and nature. Finally we question whether the use of monozygotic twins data, or data obtained from defining further levels of severity of the disease, would improve the discrimination between these two types of models.


Patterns of incidence of brain tumors in children.

A population-based community-wide study of the incidence of brain tumors in children from 1960 through 1974 was conducted in the Baltimore area. Incidence rates in boys declined from 1960 to 1974 and were higher in whites than in blacks in all age groups except children under 5 years. A peak in incidence rates was observed in white 5- to 9-year-olds and in blacks from 0 to 4 years of age. In addition, incidence rates tended to be higher in boys than in girls at all ages except at puberty-the 10- to 14-year-old age group-when rates in girls exceeded those in boys. The findings suggest that both host and environmental factors may be involved in the cause of brain tumors in children.


Variability of agar dilution-replicator method of yeast susceptibility testing.

The agar dilution method of in vitro susceptibility testing of fungi was analyzed with a Steers-type inoculum replicator, ten strains, and three drugs. The replicator reproducibly delivered the same inoculum to each series of plates. The minimal inhibitory concentrations of ketoconazole (an imidazole) and 5-fluorocytosine, but not that of the polyene nystatin, were dependent on the initial inoculum size. With the former two drugs, but not with the latter, minimal inhibitory concentrations were highly variable depending on the time of reading. Results with agar and broth dilution methods were divergent, and the differences in minimal inhibitory concentrations were variable in serial comparisons by the two methods. If the agar dilution minimal inhibitory concentrations were determined at first appearance of control growth, a commonly used end point, small variations in the time of reading (as could occur by variation in observer perception of when initial growth appears) induced large variations in the minimal inhibitory concentrations of 5-fluorocytosine and ketoconazole, particularly with rapidly growing strains. Results at 35 and 30 degrees C were similar. The differences in results with the three drugs suggest different mechanisms of action. The variability quantitated with the agar dilution method could result in variability in results between laboratories and even observers in the same laboratory.


Coeliac disease in identical twins.

Coeliac disease occurred at the same age in MZ twins. The diagnosis was confirmed by histology of the small intestine, rapid response to a gluten-free diet, and relapse after reintroduction of gluten.


[Synthesis of elastoidic fibers in the organ culture of human dermis (author's transl)].

Organ cultures of human dermal excisions placed on the chorioallantoic membrane (CAM) of incubated chick eggs showed that a elastoidic fiber type could be achieved under experimental conditions within 5 h. The stages leading up to fiber formation could very well be produced by fibrocytes as well as by the splitting of collagen fibrils. The microfibrils (lacking a periodicity and with a diameter of 60-100 A) are characterized by a strong capacity to bind carbohydrate-proteinrich complexes (proteoglycans and glycoproteins). These then aggregate to elastoidic fibers. The amorphous fiber center remains strongly attractive for binding cations. This fiber type is then compared to the (elastoidic) fibers present in senile Elastosis and Pseudoxanthoma elasticum. Finally, the possibility of using CAM-cultures as experimental means for simulating such diseases is discussed.


Estrogen-induced galactorrhea in man.

A 36-year-old man had estrogen-induced galactorrhea and oligospermia. He had been taking an unknown amount of estrogen for a year. While hypogonadism, manifested by decreased libido and potency, was apparent at the time of estrogen administration, galactorrhea appeared two months after estrogen was discontinued. Normal skull film, tomogram views of the sella turcica, and computerized axial tomography scan suggested that long-term estrogen administration caused sustained hyperprolactinemia with levels that ranged between 21 and 83 ng/mL throughout the ensuing year. Prolonged thyroid-stimulating hormone and prolactin luteinizing hormone response to luteinizing hormone-releasing hormone were believed to be evidence of a derangement in the hypothalamic control of pituitary hormone secretion. A year after he stopped taking estrogen, the patient gradually regained his potency, his prolactin level declined, the galactorrhea disappeared, and spermatogenesis returned to normal.


Prostaglandins in carrageenin-induced iridocyclitis.

In a model based on carrageenin-induced inflammation of the anterior eye chamber, prostaglandins and pronounced cellular infiltration appeared in the aqueous humor after six hours. The findings are discussed taking into account various sources of prostaglandins in the course of iridocyclitis.


Immunological alterations in the lungs of mice following ozone exposure: changes in immunoglobulin levels and antibody-containing cells.

Ozone was added to the air of the environmental chambers containing specific pathogen-free mice. At levels of 0.5 and 0.8 ppm the oxidant was seen to have inflammatory effects, as shown by rising serum albumin levels in lung lavage fluid. Fluorescein conjugated anti-heavy chain sera were used to detect cells containing IgM, IgG, and IgA in measured lung areas termed Pulmonary Units. Antigenic stimuli occurred along the airways, with significant increases of IgA-containing cells in the bronchus-associated lymphoid tissue. The numbers of IgM- and IgG-containing cells did not increase. Immunodiffusion analyses for immunoglobulins in lung lavage fluid indicated increases of IgG1, IgG2, and IgA in lung secretions. The calculation of changing Ig/Alb ratios suggested that the IgA present was largely the result of local synthesis, while IgG molecules were mainly of serum origin. Possible sources of antigenic stimuli to ozone-exposed lungs are discussed.


Capsular delamination (true exfoliation) of the lens. Report of a case.

This report describes a patient with true exfoliation of the lens capsule. Recurrent anterior uveitis eventually necessitated lens extraction from the left eye. Scanning and transmission electron microscopy demonstrated areas of capsular dehiscence and evidence of in vivo cellular degeneration. A comparison of true and pseudoexfoliation of the lens capsule is made and the term "capsular delamination" is proposed for the case reported.


Endotracheal tube ignition during laser surgery of the larynx.

The ignition of an endotracheal tube was caused by laser penetration of an unprotected portion of the tube during resection of laryngeal papillomas. We discuss the factors that contributed to the ignition, the hazards that were encountered, and the methods of prevention that were used.


The relation between patterns of ovarian follicle growth and ovulation rate in sheep.

The number and growth rate of follicles within classes based on granulosa volume were determined for ovaries taken from groups of 4-5-year-old, fine-wool Merino ewes drawn at different times of the year from a single strain flock maintained at Armidale, N.S.W. The breeding season of the flock normally extends from February to October and the mean ovulation rate rises from about 0.5 in February to about 1.8-1.9 during April-May. Ewes sampled when they were anoestrous or had one (single-ovulatory) or two (twin-ovulatory) recent corpora lutea did not differ in respect to the mean total number of ovarian follicles, the mean number of follicles in individual classes, the time for follicles to complete their rapid growth stage, or the incidence of follicle atresia. However, the ovaries of twin-ovulatory ewes contained significantly more follicles in the two terminal classes within the rapid growth stage than did the ovaries of single-ovulatory or anoestrous ewes (2.2 v. 0.9 and 1.0). This difference was attributed to the differing numbers of follicles per day entering into the rapid growth stage (5.2, 4.5 and 3.7 respectively in twin-ovulatory, single-ovulatory and anoestrous ewes).


Pituitary hormone control of implantation in the mouse.

In hypophysectomized pregnant mice replacement therapy designed to mimic the normal physiological situation showed that FSH in combination with either prolactin or LH, or prolactin plus LH, could initiate implantation in the absence of the pituitary gland. No pituitary hormone was by itself capable of achieving this result. The combination of prolactin with FSH gave better results than a combination of LH with FSH. Prolactin from sheep, cattle or rats was equally effective in combination with rat FSH in initiating implantation. In mice exhibiting suckling-induced delay of implantation this delay was terminated by injection of FSH. GH by itself or in conjunction with other hormones had no significant effect on implantation or on any of the other parameters associated with implantation that were measured. On the basis of these experimental results it is suggested that prolactin and LH are involved with progesterone production and FSH with oestrogen production, both of which are required for implantation in the mouse.


[Photosensitization in cattle grazing on pastures of Brahciaria decumbens Stapf infested with Pithomyces chartarum (Berk. & Curt.) M.B. Ellis].

Aspects of photosensitization in bovines grazing on pastures of Brachiaria decumbens Stapf infested with Pithomyces chartarum (Berk. & Curt.) M.B. Ellis infested all pastures 45(2):117-136, 1978. This paper reports experimental studies on photosensitization in bovines grazing on different pastures of Brachiaria decumbens Stapf in the "Cerrados" region (Planaltina, DF). Climatic conditions, zinc content and occurence of fungi on pastures were investigated. Pithomyces chartarum (Berk. & Curt.) M.B. Ellis infested all pastures examined. Photosensitization was observed in one animal maintained on a pasture of B. decumbens formed with seeds from Australia. Clinical and necropsy data were similar to those related in literature for sporidesmin-intoxicated animals. An isolate of P. chartarum and samples of bovine bile were assayed for sporidesmin presence.


A 1,4-beta-glucan glucanohydrolase from the cellulolytic fungus Trichoderma viride QM 9414. Purification, characterization and preparation of an immunoadsorbent for the enzyme.

A 1,4-beta-glucan glucanohydrolase (EC 3.2.1.4) was isolated from culture filtrates of the fungus Trichoderma viride QM 9414 by molecular-sieve chromatography on Bio-Gel P-30, ion-exchange chromatography on DEAE-Sephadex A-50 and isoelectric focusing in a density gradient. Polyacrylamide-gel electrophoresis at two different pH values, analytical isoelectric focusing in a polyacrylamide-gel slab and molecular-sieve chromatography of the reduced and alkylated enzyme in a denaturing medium indicated a homogeneous protein. The enzyme has a mol.wt. of 51,000 and is not a glycoprotein. The pI was found to be 4.66 at 23 degrees C. Antiserum against the purified enzyme was prepared and the amount of enzyme in the original filtrate was determined by rocket immunoelectrophoresis to be about 50mg/liter. An immunoadsorbent made from CNBr-activated sepharose 4B and antiserum affords a rapid and highly specific purification of the enzyme.


Reactivities of hydroxylamine and sodium bisulphite with carbonyl-containing haems and with the prosthetic groups of the erythrocyte green haemoproteins.

The reactivities of alkaline NH(2)OH and neutral NaHSO(3) with carbonyl and olefinic groups conjugated with the tetrapyrrole nucleus of haems were studied. The reactions were carried out with 2-3nmol of haem a, spirographis haem, isospirographis haem, 2,4-diacetyldeuterohaem and protohaem. Vinyl side chains were found to be insensitive to the chemical action of both alkaline NH(2)OH and neutral NaHSO(3). The formyl-containing haems reacted rapidly with both reagents at room temperature, as evidenced by sizable hypsochromic shifts of the reduced pyridine haemochrome spectrum. In less alkaline solution, the reactions of these formyl-containing haems with NH(2)OH were much slower. 2,4-Diacetyldeuterohaem reacted with alkaline NH(2)OH, but not with neutral NaHSO(3). These rapid, simple and straightforward tests are readily usable in differentiating among formyl, acetyl and other electron-withdrawing side chains conjugated with the tetrapyrrole ring of haems. We applied these observations to an investigation of the two unique prosthetic groups of the bovine erythrocyte green haemoproteins. The prosthetic groups of these two proteins were isolated and spectrally characterized. Under the conditions used, the haems did not react with either NH(2)OH or NaHSO(3), but were altered by dithionite, suggesting that the previous interpretation that a formyl group was present [Hultquist, Dean & Reed (1976) J. Biol. Chem.251, 3927-3932] may have been premature. These studies also provide evidence that the alpha-hydroxyfarnesylethyl side chain of haem a affects the alpha-band maximum, but not the beta- or Soret bands of the reduced pyridine haemochrome spectrum of haem a.


Preparation of [32P]phosphatidylcholine and [32P]lysophosphatidylcholine by using soya beans.

This method describes a procedure that can be carried out easily to obtain large amounts of [32P]phosphatidylcholine and [32P]lysophosphatidylcholine. The method involves germinating soya beans in the presence of [32P]Pi. The yield was 0.58% for [P]phosphatidylcholine and 0.52% for [32P]lysophosphatidylcholine, and the specific radioactivity of both was 10(7) d.p.m./mumol.


[Uremic-hemolytic syndrome: clinical and pathological observations of a case (author's transl)].

A case of uremic hemolytic syndrome observed in a 20 months old child has been investigated from the clinical and pathological point of view. All specific clinical manifestations of the syndrome were present as well as the pathognomic pathological finding of a renal trombotic microangiopathy. In addition a generalized lymphoadenopathy likely related to a previous vaccination, was also found. The possible role of such an immune reaction in the pathogenesis of the syndrome in the present case is discussed.


[Use of hypnotism in transcutaneous renal biopsy. Preliminary results].

We wish to point out the outstanding importance of kidney biopsy in diagnosis of kidney diseases and enphasize the fact that it is very important for the patient to give one's full cooperation, in order to achieve the most successful results. Anxious subjects and children usually do not give this cooperation owing to their excessive emotional reactions to the special situation of the biopsy and so we think it useful to induce beforehand a hypnotic state in them, hoping that this would make it possible to carry out the research with the usual transcutaneous technique. In this research, which is to be considered as preliminary, ten patients were examined, nine of whom aged from three to fourteen and one aged forty-six. Eight subjects, out of ten, reached such a degree of hypnotic depth that it was possible to carry out the biopsy in a few minutes without noteworthy difficulties. The high ratio of successful cases and the lack of any considerable complications in their experiments enable the Authors, though still waiting for a wider range of data, to suggest since now the use of hypnosis whenever the patients prove reluctant to cooperation.


Treatment of hypertrophic obstructive cardiomyopathy with verapamil.

Twenty-two patients with hypertrophic obstructive cardiomyopathy were treated with the calcium inhibitor, verapamil, which was administered in a mean oral dose of 480 mg per day. After an average of 15 months of treatment (4 to 24 months), the QRS amplitude in the electrocardiogram was significantly reduced from 4.2 to 3.8 mV. Heart volume calculated from chest x-ray films in the supine position decreased significantly from 858 to 766 ml per 1.73 m2. In 10 patients, follow-up heart catheterisation showed a decrease in left ventricular muscle mass in 7 patients and a slight increase in 3 patients. Coronary artery diameter decreased in 7 patients, increased in 1, and was unchanged in 2. The reduction in coronary artery diameter is considered to be a consequence of a reduced heart muscle mass. From all available clinical data it is concluded that verapamil treatment is superior to beta-blocker therapy.


Evidence that cells from experimental tumours can activate coagulation factor X.

The procoagulant activity of cells from some experimental tumours isolated in culture or in single-cell suspensions from ascitic fluid was investigated. Cells from Lewis lung carcinoma (primary and metastasis), Ehrlich carcinoma ascites and JW sarcoma ascites were able to shorten markedly the recalcification time of normal, Factor VIII- and Factor VII-deficient but not of Factor X-deficient human plasma. The same cells generated thrombin when mixed with a source of prothrombin and Factor X, absorbed bovine serum (as a source of Factor V), phospholipid and calcium chloride. Thrombin formation was not influenced by the presence of Factor VII. Cells from Sarcoma 180 ascites were completely inactive in both test systems. It is concluded that cells from some experimental tumours have the capacity to activate Coagulation Factor X directly. These findings suggest the existence of an alternative "cellular" pathway in the initiation of blood clotting distinct from both the intrinsic and extrinsic mechanisms.


Effect of varying amounts of ethinyl oestradiol in the combined oral contraceptive on plasma sex hormone binding globulin capacity in normal women.

The plasma sex hormone binding globulin (SHBG) capacity has been measured in 52 normal women, 11 women on various oral contraceptives containing 50 micrograms of ethinyl oestradiol and 11 women on oral contraceptives containing less than 35 micrograms of ethinyl oestradiol. The results show that women on oral contraceptives containing 50 micrograms of ethinyl oestradiol have a significantly raised SHBG capacity (p less than 0.005) whereas those patients on oral contraceptives containing 35 micrograms or less of ethinyl oestradiol have SHBG capacities which do not differ significantly from normal ovulating women (p greater than 0.05). Thus the 35 micrograms pill interferes less with bound/unbound sex steroid ratios than does the 50 micrograms pill.


Protein nutrition of growing lambs. 2. Effect on nitrogen digestion of supplementing a low-protein-cellulosic diet with either urea, casein or formaldehyde-treated casein.

1. Lambs with cannulas in the duodenum and ileum were allowed free access to one of four diets: a basal diet of oat hulls and solka floc, or the basel diet supplemented with either urea, urea plus casein or urea plus formaldehyde-treated (HCHO)-casein. Mean nitrogen intake was 1.9 g N/d for the basal diet and 15.0. 32.4 and 36.9 g N/d respectively for the other diets. 2. The rate of irreversible loss of ammonia from the rumen pool estimated using 15NH4+ was highest on the casein diet (33 g NH3-N/d) by comparison with 18 g NH3-N/d for the urea and HCHO-casein diets and 7 g NH3-N/d for the basal diet. 3. The proportions of bacterial and protozoal N in the rumen derived from rumen ammonia did not differ significantly between the supplemented diets and were 0.66 and 0.52 respectively. 4. Estimation of 15N flowing to the duodenum during continuous infusions of 15NH4+ into the rumen indicated considerable ammonia absorption from the rumen on all the diets. Greatest absorption of ammonia (21 gN/d) apparently occurred in animals on the diet supplemented with urea and casein. 5. The estimated microbial non-ammonia-N (NAN) flowing out of the rumen per unit organic matter fermented in the rumen (FOM) was similar on all diets, i.e. 21.3 (+/- 1.09) g N/kg Fom. the requirement for dietary fermentable N for microbial N production on these diets was 1.2 (+/- 0.07) g N/MJ ME. 6. The flow of NAN into the duodenum and through the ileum, and total N in the faeces was significantly influenced by the form of N supplementation. The flow of NAN into the duodenum for the HCHO-casein diet (27 g N/d) was more than twice that for the other diets (11 g N/d). The flow of NAN through the ileum and excretion of total N in the faeces was also greater with the HCHO-casein diet than with all other diets. The apparent digestibility of NAN in the small intestine ranged between 0.62--0.66 for all diets. 7. Urea and casein supplements were apparently completely degraded in the rumen. In contrast, the HCHO-casein was almost completely resistant to degradation in the rumen and only 65% of the HCHO-casein was digested in the small intestine. 8. Protein absorbed : energy absorbed (expressed as NAN digested in the small intestine/MJ ME) was calculated to be 5.5 (+/- 0.70) for the basal, urea and urea-plus-casein diets, and 11.6 (+/- 1.71) for the urea-plus-HCHO-casein diet.


Regulation of phospholipase A2 activity by the lipid-water interface: a monolayer approach.

Interfacial regulation of phospholipase A2 activity on lecithin monolayers was investigated by using radioactively labeled enzyme. Labeling of the protein with 125I did not produce a change of the enzyme and protein properties as compared to the 3H fully amidinated phospholipase A2. The induction time observed during pre-steady-state kinetics reflects the rate-limiting step of the penetration of the enzyme in the interface. This penetration is reversible. However, in the surface pressure range where the enzyme is able to hydrolyze the lecithin films, the desorption of the protein from the film is slow as compared to the adsorption. Below a surface pressure of 10 dyn/cm nonspecific adsorption occurs. Using lecithins with fatty acids of different chain lengths, we have shown that the kinetics of the penetration process is governed by the packing density of the substrate molecules independent of the surface pressure. However, the steady-state surface concentration of the enzyme increases with the fatty acyl chain length of the lecithin, indicating that hydrophobic interaction occurs between phospholipase A2 and the lipid molecules at the interface. From the lecithins used pancreatic phospholipase A2 preferentially splits substrate molecules with nine carbon atoms in the acyl chain.


Amino acid substitutions of the NH2-terminal Ala1 of porcine pancreatic phospholipase A2: a monolayer study.

Previously it has been shown that the binding of porcine pancreatic phospholipase A2 to lipid-water interfaces is governed by the pK of the alpha-NH3+ group of the N-terminal alanine. Chemically modified phospholipases A2 in which the N-terminal Ala has been replaced by D-Ala or in which the polypeptide chain has been elongated with DL-Ala no longer display activity toward micellar substrate. The activity of DL-Ala-1-, [D-Ala1]-, and [Gly1]phospholipases A2 on substrate monolayers, which allow a continuous change in the packing density of the lipid molecule, was investigated. At pH 6 [Gly1]phospholipase A2 behaves like the native enzyme on lecithin monolayers. DL-Ala1- and [D-Ala1]phospholipases A2, although they are active in this system, showed a weaker lipid penetration capacity at this pH. Studies on the pH and Ca2+ ion dependency of the pre-steady-state kinetics and of the activity of these radiolabeled proteins showed that [D-Ala1]phospholipase A2 does not possess a second low-affinity site for Ca2+ ions in contrast to the native phospholipase A2. This second low-affinity Ca2+ binding site, which is also absent in [Gly1]phospholipase A2, is induced in the latter enzyme by the presence of lipid-water interfaces.


Sequence complexity of polyadenylated ribonucleic acid from soybean suspension culture cells.

The sequenc complexity of total poly(A) RNA from a higher plant system, soybean cultured cells, was determined. Labeled cDNA synthesized from the poly(A) RNA hybridized exclusively with the unique sequence component of total soybean DNA. Analysis of the hybridization reaction between cDNA and the poly(A) RNA template revealed three abundance classes in the poly(A) RNA. These classes represent 18, 44, and 38% of the poly(A) RNA and contain information for approximately 60, 1900 and 30,000 different 1400-nucleotide RNA molecules. From these results, the total sequence complexity of poly(A) RNA was estimated to be 4.5 X 10(7) nucleotides. Saturation hybridization of labeled unique DNA with RNA showed that the total cell RNA represents 12.4% of the unique DNA sequence complexity, or 6.4 X 10(7) nucleotides, while poly(A) RNA respresent 8.7% of the unique DNA sequence complexity, or 3.3 X 10(7) nucleotides. Thus, it is estimated that 50--70% of total RNA sequence complexity is contained in poly(A) RNA in these cells.


The effect of nystatin on active transport in Rhodotorula glutinis (gracilis) is restricted to the plasma membrane.

The effect of the polyene antibiotic nystatin on the energy-requiring transport of substrates in the obligatory aerobic yeast Rhodotorula glutinis (gracilis) is restricted to its interaction with the plasma membrane, whereas the energy metabolism in mitochondria remains unaffected by the antibiotic. A method for preparation of the mitochondrial fraction from this yeast is described.


Fusion of phospholipid vesicles in association with the appearance of lipidic particles as visualized by freeze fracturing.

The addition of Ca2+ to small unilamellar vesicles of an equimolar mixture of egg phosphatidylcholine and cardiolipin induces fusion of these vesicles in association with the appearance of lipidic particles on the fusion sites.


Absorbability of plant sterols and their distribution in rabbit tissues.

Rabbits were fed a low cholesterol diet containing 2% plant sterols for 10 weeks to determine the absorbability of these sterols and their deposition in the tissues. We found campesterol and beta-sitosterol in the blood and tissues. The plasma campesterol levels were 4.34--13.3 mg/100 ml, whereas, beta-sitosterol levels were 0.41--1 mg/100 ml. Stigmasterol was not detected. The total plasma plant sterol concentration was about 10% of the total plasma sterol. The mean terminal plasma cholesterol concentration averaged 60% higher (55 vs. 88 mg/100 ml, P less than 0.001) than the mean initial value. Campesterol was the preponderant sterol in all tissues studied, including the aorta. Sitosterol was found in small amounts in the tissues of the abdominal organs. Stigmasterol was not detected in any tissue studied. Esterified campesterol and sitosterol were detected in trace amounts in most tissues. Campesterol and sitosterol, particularly the former, accumulated in the tissues including the aorta.


Ammonia overloading in hepatocytes isolated from liver of fetal and adult rats.

Ammonia overloading was investigated during glucose and fructose metabolism in isolated hepatocytes under a variety of metabolic conditions. In all assay conditions, the glycolytic flux and oxygen uptake was not modified by 10 mM ammonia. In hepatocytes isolated from rats fed as libitum, the presence of ammonia caused a decrease in the production of lactate (pyruvate); this effect was not observed in anaerobic incubations, in hepatocytes isolated from starved animals, or in fetal hepatocytes. In spite of an overproduction of urea, ammonia detoxification also takes place by the synthesis of alanine, glutamate and aspartate. Addition of 1 mM aminooxyacetate, an inhibitor of aminotransferases, to the incubation medium prevents the formation of these amino acids, and also prevents the decrease of lactate in hepatocytes isolated from fed animals.


Oxidation and synthesis of fatty acids in human and rat placental and fetal tissues.

The rat fetus (day 21 of pregnancy) covers its fatty acid (FA) demands at equal amounts both by maternal-fetal FA transfer and fetal FA synthesis. At the end of the first trimester the human fetal FA synthesis is too small to cover the fetal FA requirements. Therefore, the transfer of FA from the mother to the fetus seems to be the predominant source of fetal FA. The FA oxidation is greater than the FA synthesis in human and rat placenta as well as in the human fetus at the end of the first trimester, whereas the rat fetus (day 21 of pregnancy) oxidizes and synthesizes FA at equal amounts.


Influence of environmental conditions and handling on the temperature rhythm of the rat.

The necessity for considering environmental influences when performing and evaluating animal experiments was confirmed by using a wireless biotelemetry unit. Long-term measurements of nuclear temperature rhythms showed temperature rises of several tenths of a degree and in extreme conditions of up to 1.4 degrees C when animals were subjected to normal daily and experimental procedures.


Thrombotic thrombocytopenic purpura and dose of plasma exchange.

Four patients with thrombotic thrombocytopenic purpura (TTP) were treated by plasma-exchange transfusion, three of whom recovered completely. Because previous reports in the literature describing exchange transfusion as treatment for TTP have demonstrated variable success rates, particular attention was given to "dose" and frequency of plasma exchange. Evans blue dye studies established a measure of "dose" under conditions of varying efficiency. Serum LDH activity was found to be diminished by plasma exchange, and the rate of return of serum LDH activity reflected residual disease activity. The magnitude of LDH activity reduction correlated with the adequacy of dose of plasma exchange and was an indicator for the need of repeated daily exchanges. Failure to obtain a spontaneous increment in platelet count also suggested the need for additional exchanges and/or larger dose of exchange. There is a need for a standard expression of dose of plasma exchange. Utilizing these markers (LDH, platelet count), it may be possible to improve the survival in TTP if adequate dose and frequency of plasma exchange are used.


Sex-related and cyclic variation of trace elements in rat hypothalamus and pituitary.

The concentrations of 7 trace elements--iron, copper, zinc, arsenic, selenium, bromine, and rubidium--in rat hypothalami and anterior pituitaries were measured by X-ray fluorescence spectrometry. Male, cycling female, and oophorectomized animals were studied under different conditions of reproductive function. Hypothalamic zinc and copper concentrations both rose between proestrus and estrus days and fell again at diestrus. After castration, concentrations of iron, copper, and arsenic were decreased in both pituitary and hypothalamus, while zinc concentrations rose. Male rats had lower pituitary concentrations of iron, copper, zinc, arsenic, and rubidium than cycling females. Under these hormonal manipulations, hypothalamus zinc concentration and gonadotropin secretion appear to be correlated. While injections of copper salts into the hypothalamus can also stimulate gonadotropin release, we did not observe any consistent relation between endogenous hypothalamic copper concentrations and gonadotropins.


Relationship between carbon source and susceptibility of Cephalosporium acremonium to selected amino acid analogues.

The susceptibility of Cephalosporium acremonium to selected amino acid analogues was markedly influenced by the carbon source used in the test media. Lysine hydroxamate, beta-hydroxy norvaline, and hexafluorovaline were toxic when tested with ribose, ribose or fructose, and ribose or galactose, respectively. In contrast, thialysine and thiaisoleucine inhibited C. acremonium with glucose, fructose, galactose, sucrose, mannitol, sorbitol, and soluble starch. Neither of these analogues was toxic at levels tested when glycerol was used as a carbon source. The minimal inhibitory concentrations (MIC) of thialysine, homoserine, and alpha-methylserine were greater than 1000, greater than 1000, and 250 microgram/mL, respectively, with glycerol. In contrast, the MIC values for the same three analogues were 31, 62, and 125 microgram/mL, respectively, with mannitol. The matching of the carbon sources with the specific amino acid analogues expands the number of analogues useful for selecting derepressed mutants. Thialysine-resistant mutants (tlysR) of C. acremonium which excrete lysine were isolated on a medium containing mannitol.


Determination of plasma erythropoietin levels: an early marker of tumor activity.

A young female patient developed erythrocytosis during the third recurrence of a cerebellar hemangioblastoma. Elevated erythropoietin levels were found in the patient's plasma with normalization after resection of the tumor. High erythropoietin titers were also found in the tumor saline extract. A fourth recurrence of the tumor was heralded by a rising plasma erythropoietin level and gradual erythrocytosis despite the absence of change in the clinical picture or the brain scan. In this case, serial plasma erythropoietin determinations served as a useful early marker of the tumor activity.


Cancer in persons with inherited blood coagulation disorders.

In order to assess the influence of an inherited blood coagulation disorder in individuals who developed cancer, a mail survey of physicians who care for individuals with a bleeding diathesis was evaluated. Sixty-one individuals in an estimated population of 10,500 with both disorders were identified. An apparent increase in the incidence of cancer in the genitourinary and musculoskeletal systems was noted. However, in the largest group ( hemophilia) the primary site of cancer was similar to an age and sex matched population. There did not appear to be a change in the onset of metastatic disease in these individuals, as compared to an individual with cancer who did not have an inherited blood coagulation disorder.


Cutaneous angiosarcoma of the head and neck.

Between 1920 and 1970, 13 patients (7 men and 6 women) with cutaneous angiosarcomas of the head or neck were treated at the Mayo Clinic; the mean age of the patients was 66 years. Three clinical patterns were noted: a superficial spreading type, a nodular type, and an ulcerating type. There were no predisposing benign lesions; however, in one patient, angiosarcoma developed in an area of previously irradiated skin. Three modes of therapy were used: surgery alone, radiation alone, and surgery with postoperative irradiation. Of the 13 patients, 2 survived more than 5 years and 2 were alive within 1 year of therapy. Because cervical lymph node spread is common, lymph node clearance is recommended for patients with lateralized lesion or with palpable lymphadenopathy at presentation.


Analysis of human cancer DNA's for DNA sequence of human adenovirus serotypes 3, 7, 11, 14, 16, and 21 in group B1.

We have investigated whether Group B human adenoviruses (Ad) (Ad3, Ad7, Ad11, Ad14, Ad16, and Ad21), which are widespread in the human population and are tumorigenic in hamsters, may play a role in human cancer. Hybridization of Ad7-radiolabeled DNA with DNA's from an Ad7-induced primary hamster tumor and from two cell lines (5728 and Ad7 P-cell) established from Ad7-induced hamster tumors indicated multiple copies per cell of 17, 30 to 36, and 20%, respectively of the Ad7 genome. Thus, cells transformed by Group B Ads resemble cells transformed by Group C and Group A Ad's in that they retain multiple copies of a variable fraction of the viral genome. These model studies suggest that possible Group B Ad-induced human cancer cells should contain one or more copies of virus DNA per cell. Therefore, we assayed human cancer DNA's for Ad sequences, by highly sensitive "saturation-hybridization" reactions with Ad7 or Ad11 DNA (4 X 10(6) to 2.1 x 10(8) cpm/microgram). We concentrated on cancers of the respiratory and digestive systems, because these systems are the most common sites of infection by Group B Ad's. In 8 independent experiments, no Ad7 sequences were detected in DNA's from 16 normal lung tissues, 18 normal tissues of the digestive system, 34 cancers of the respiratory system, 19 cancers of the digestive system, 11 cancers of the urinary system, 5 cancers of the genital system, 3 cancers of the breast, and 6 Hodgkin's lymphomas. Reconstruction controls with added Ad7 DNA indicated that about 0.05 to 0.1 copy of Ad7 DNA per cell should be detected. Ad11 is strongly implicated as a cause of acute hemorrhagic cystitis. In two independent experiments, no Ad11 sequences were detected in DNA's from 9 carcinomas of bladder, 10 carcinomas of prostate, 24 carcinomas of kidney, 3 hypernephromas, 3 Wilms' tumors, or 2 normal kidneys. Reconstruction experiments indicated that the cancer DNA assays had a sensitivity of 0.05 to 0.1 copy of Ad11 DNA per cell. The DNA's of Group B Ad's are greater than 85% homologous by hybridization; thus, these results are applicable to all Group B serotypes. Our data provide evidence (but not formal proof) that none of the human cancers that we analyzed were induced by Group B Ad's. These tumors represent about 50% of the tumors that affect humans. The possible involvement of Group B Ad's in other less common forms of human cancers is under investigation in our laboratory.


Impaired rate of left ventricular filling in idiopathic hypertrophic subaortic stenosis with atrial fibrillation.

The external carotid pulse and the phonocardiogram were recorded in a 48-year-old man with idiopathic hypertrophic subaortic stenosis and atrial fibrillation. The degree of obstruction of left ventricular outflow was assessed by the depth of the mid-systolic dip, the length of the left ventricular ejection time and the intensity of the systolic murmur. The correlation found between the degree of outflow obstruction and the length of the preceeding diastole was interpreted in terms of the Frank-Starling mechanism, i.e. augmented diastolic filling led to an increase in the force of contraction and hence to an increase in muscular obstruction to outflow. The observation that this relationship held also for long diastoles suggested that the left ventricle was not completely filled during diastoles of middle length, probably because of the low diastolic distensibility of the stuff and hypertrophic myocardium.


Discrete fibromembranous aortic stenosis in middle age. Natural history and case report.

Discrete fibromembranous subaortic stenosis may be severe at birth, progress in severity irrespective of the initial degree of obstruction, and morphologically change during the course of its natural history. Initial status, progression of the lesion and perhaps later development of fibromuscular (tunnel) and/or asymmetric septal hypertrophy may all contribute to a shortened life span and account for the different incidence of fibromembranous subaortic stenosis in children and adults. In the case reported here, a patient survived into the sixth decade with a discrete fibromembranous subaortic stenosis, which led to typical as well as unusual echocardiographic findings.


Viability of the cervical epithelium during carcinogenesis in mice.

Autoradiograms of histological specimens from the cervix of seventy-five mice were analysed after in vivo injection with an RNA precursor. All nucleated, non-pyknotic cells and some mitotic figures were labelled, which suggested that the tissue was metabolically active (i.e. viable). Only the uppermost epithelial pyknotic cells were devitalized, as deduced by the morphological appearance of the cells and by the absence of label. The viability of the whole epithelium suggests that the previously reported focal distribution of proliferating and non-proliferating areas in the cervical epithelium of mice is a genuine phenomenon.


Effects of halothane on microtubules in the sciatic nerve of the rat.

The effect of halothane and colchicine on microtubule repolymerisation after exposure to cold has been examined in the sciatic nerve of the rat. Myelinated axons showed a significant decrease in microtubule numbers and density after exposure to both 20 mM halothane and 10(-5) M colchicine; exposure to both agents simultaneously produced a further significant reduction when compared to halothane alone. It is suggested that halothane can interfere with microtubule repolymerisation in mammalian axons possibly in a similar way to that described in invertebrates.


An ultrastructural study on a new type of hepatic perisinusoidal cell in fish.

A new type of perisinusoidal cell containing numerous microfilaments is described for the first time. It is found in abundance in the livers of both marine and freshwater fish. These perisinusoidal cells are situated within the space of Disse and adhere firmly through desmosomes both to sinusoidal endothelial cells and to hepatocytes. The cytoplasmic microfilaments are striking and make these cells readily distinguishable from the perisinusoidal fat-storing cells of Ito. Although the function of these cells is not known, the observations presented here suggest that they may provide a supportive framework within the liver.