[Partial surgery of carcinomas of the glottis. Results and prognosis (author's transl)]. The authors present a computerized study of the prognosis of 132 cases of carcinoma of the glottis treated by vertical, partial surgery and seen over a period of 1 to 15 years at the Laennec Hospital. After defining the percentage survival at 3.5 in 10 years, the authors studied the causes of death and showed that, after 5 years, it is still deaths due to malignant recurrence which influenced the vital prognosis. These local, lymphnode and metastatic oncological failures are subsequently analyzed on the basis of clinical, surgical and histological parameters as well as in terms of the course of the disease. Such analysis makes it possible to draw the distinction between local recurrence and a second local tumor localization, and pulmonary metastases from a second pulmonary localization. Finally, the prevention of rare lymphnode recurrences is considered in terms of specific surgery for this purpose.


[Topographical diagnosis of facial paralysis (Bell's palsy) (author's transl)]. Topographical diagnosis using Schirmer's test and measurement of the stapes reflex was carried out in a series of 45 cases of Bell's palsy. The aim of this study was to define the exact location of the nerve lesion in order to guide the possible choice of surgical decompression of the facial nerve. The authors noted the existence of a geniculate or suprageniculate lesion in 62% of cases. A study of the literature shows marked disagreement between the various publications. This leads to discussion of the value and interpretation of topographical tests.


[Facial nerve tumors: three cases (author's transl)]. The first one is a neurofibroma associated with a Charcot-Marie Tooth's disease involving all the tympanic segment of the facial nerve: extirpation and graft. Improvement of facial motricity to 42%. The second one is a small Schwannoma lateral to tympanic segment: extirpation without paralysis. The third is a large Schawannoma of the tympanic mastoïd segments involving the facial nerve to its division in the parotid gland, and with a limited extension in the cerebello-pontine angle. Extirpation and graft. Discussion and recent bibliography.


[Scintigraphy with Technetium 99. Picture of hot nodule on cancerous nodule (author's transl)]. The authors explain a new case of discordance between scintigraphy with Technetium 99 and Iodin 131. Medullary carninoma with appearance of hot nodule with Technetium and cold with Iodin.


[Hemangiopericytoma of the parotid in the child (author's transl)]. A very rare case of localization in a large salivary gland (parotid) of a hemangiopericytoma in a 9 and 1/2 year old child. Detailed and discussed histopathological examinations resulted in a diagnosis of hemangiopericytoma (Nézelof, Gérard-Marchant). Despite wide excision by parotidectomy, there was a local recurrence two years later.


[Jugulo-carotid glomus and false glomus tumors. Three cases (author's transl)]. A carotid glomus is, classically, a firm, non-pulsatile tumor situated just behind the carotid bifurcation. Erreurs are possible: -- the tumor may be pulsatile, -- the site impossible to define if the tumor is large. Carotid arteriography is essential, in the case of a glomus tumor showing widening of the carotid bifurcation. Treatment is surgical, with possible ablation or reconstruction of the carotid axis. Such surgery must be performed in a specialized centre.


[Specific ENT involvement in a case of angio-immunoblastic adenopathy (author's transl)]. The authors report the case of a 78 year old man with an unusual localization (soft palate and tonsil) of an angio-immunoblastic lymphadenopathy. Clinically, the syndrome combines fever, a marked change in general condition, multiple lymphadenopathy and skin rash. From a laboratory standpoint, the picture is dominated by polyclonal hypergammaglobulinemia, often associated with a hemolytic anemia. Histologically, only lymphnode biopsy allows the diagnosis to be made, with the following findings: disruption of the normal architecture of the node, marked vascular neogenesis, presence of acidophilic interstitial substance, lympho-plasmo-immunoblastic proliferation. The course is in general rapidly fatal despite corticosteroids and multiple chemotherapy.


[Ultrastructural study of the dogfish mature egg-capsule gland zones secreting proteic and glycoproteic material (author's transl)]. The ultrastructural study of the zones (D, E, F1) of a dogfish mature egg-shell gland secreting proteic and glycoproteic material brings evidence of a wide range of secretions. Besides the two types of grain found in each of the two zones D and E (respectively spiralled and heterogeneous) a second type of heterogeneous grain as well as a fourth one composed of tiny dense particles are present in zone E. A fifth type of grain is revealed in zone F1. The Golgi apparatus is undoubtly involved in the formation of F1 grains and of both heterogeneous grains, but seems to be irrelevant to zone E secretion of dense grains. As regards spiralled grains there is no evidence of the first stage of their formation in the mature gland. After this first ultrastructural study, the grains specifically involved in the formation of the collagenic protein cannot yet be positively identified.


[Role of the mesenchyme in the fusion of palatine shelves (author's transl)]. Na2 35SO4 was either injected to pregnant mice or added to a "Wolff and Haffen" culture medium. In various experiments, palatine shelves and half-lips remained one hour on this labeled culture medium. They were thereafter associated to another labeled fragment, either to their homologous shelf in a homotypical culture, or to a half-lip in heterotypical culture. In the same way, labeled half-lips were coupled to unlabeled palatine shelves. In all these cases, the mesenchyme was labeled by the tracer while the epithelial cells remained empty. In the medio-palatine epithelium, some dislocations could be noticed between the cells. These gaps were filled by the labeled mesenchyme with which they were in continuity. At this level the tracer appeared on the external surface. In the homotypical associations, it invaded, through these channels, the labeled antagonistic explant; in the heterotypical associations, lips plus palatine shelves, the labial epithelium prevented all the penetrations, except when alterations occurred, due to a long lasting culture. The role of the mesenchyme in the process of fusion and in the possible building of a surface coating is discussed.


The marginal band and its role in the ellipsoidal shape of Geochelone carbonaria erythrocytes. Erythrocytes from a chelonian (Geochelone carbonaria) were submitted to physical and chemical treatments. Observations of their change in shape from ellipsoidal to spherical were made by means of light microscopy. A 100% change to the spherical shape was attained with erythrocytes under high temperature treatment (42 degrees C) for 45 min., and at room temperature (29 degrees C) plus colchicine, for 60 min. Erythrocytes kept at room temperature present changes in shape while those kept at low temperature (10 degrees C) did not exhibit significant changes in their original ellipsoidal shape, but displayed an intact marginal band (MB). By direct examination the diameter of microtubules was found to be nearly 300 A in the dissociated form and 0.70 mu when bundled. In cross section the value found for microtubule diameter was up to 210 A. These measures are compatible with those found by several other authors. Counting of microtubules by ultrathin sectioning indicated approximately 70 tubules per cell, a value that is higher than that found in other species. By means of electron microscopy the marginal band can be observed intact or dissociated into several dense rings formed by parallel microtubules running nearly or accompanying the periphery of the stroma. Temperature and colchicine are responsible for the depolymerization of the microtubules. In the stroma of spherical erythrocytes a dense peripheric fold can be observed but microtubules were never found. It is suggested therefore that the role of the marginal band is essential to maintain the ellipsoidal shape of chelonian erythrocytes.


[Histoenzymological contribution to the study of the rat blood-brain barrier (author's transl)]. The localization of non-specific alkaline phosphatase and cholinesterase activities evidenced in capillaries endothelium of the Rat brain have been compared in cerebral areas with or without the blood-brain barrier (BBB). There is a good topographical correlation: structures devoid of BBB (caudal part of the subfornical organ, choroid plexus, area postrema) do not display any non-specific cholinesterase activity with photonic microscope methods and an intense alkaline phosphatase activity; whereas structures with BBB (cortex, subcommissural organ, rostral part of the subfornical organ) show both enzymatic activities. At the ultrastructural level, more sensitive methods allow to disclose a non-specific cholinesterase activity in the reticulum endoplasmic cisternae and in the nuclear membrane in all endothelial cells. Alkaline phosphatase activities are present in the capillaries endothelium and in the conjonctive cells of pericapillaries spaces which exist in the circumventricular organs. Besides, these activities are closely related with the lateral and basal plasmalemmas of the choroidal cells responsible for the blood-cerebro-spinal fluid barrier. The apical plasmalemma is almost devoid of enzymatic activity. This result confirms the noticeable polarity of the choroidal cells, both morphologically and cytochemically.


[In vivo evidence for bispecific myotubes containing chick and quail nuclei (author's transl)]. The nuclear specificity of 12 day embryonic skeletal muscle cells has been studied in ectopic limbs that developed after implantation of quail limb somatopleural mesoderm into chick hosts. In eleven cases, the nuclearity of the myotubes was homospecifically of chick type. In the remnant eight cases, the musculature was heterospecific, the myotubes being homospecific and constituted by chick or quail nuclei or the myotubes being heterospecific and containing at random chick and quail nuclei. The heterospecific multinuclearity was analyzed in 85 portions of myotubes. The degeneration of numerous heterospecific muscle cells was attested by the shrinked and hyperchromatic states of the nuclei and by the fragmentation of the sarcoplasm that contained cellular debris. Nevertheless, there is no correlation between myotube degeneration and heterospecificity, because the same necrotic figures are observed in chick host homospecific myotubes that have reached the same degree of development.


[Intracranial tumors in childhood. Study of 106 cases]. The authors analyze 106 intracranial tumors occurring in patients from 0 to 15 years of age. This study was carried on during the period from 1962 up to 1977. In 85 cases the diagnostic work up was made on clinical, radiological, and histological grounds; the remaining 21 cases had their diagnosis based solely on clinical and radiological evidence. Observations involving incidence according to age, sex, localization and histological types are made. The signs and symptoms and supplementary examination are discussed. The frequency of primary intracranial tumors in children under 1 year of age is stressed.


[Brain changes in leukemias. Histopathological aspects of choroid plexus involvement]. In the study of 38 cases of leukemia, neoplastic infiltration of the brain was the most frequent lesion, occuring in 70,5%, compared to 48,5% for hemorrhage. The leptomeninges were the most frequent site of leukemic infiltration followed by the choroid plexus (57,8%) and the nervous tissue (50%). In few cases leukemic infiltration of choroid plexus was seen in the absence of meningeal involvement. Very often the leukemic infiltration of the CNS courses without clinical manifestations. The paper points out the importance of the cytologic study of the cerebro-spinal fluid as a routine procedure in cases of leukemia, since it is well known that the therapeutic agents have difficulty in penetrating the blood-brain barrier and that foci of CNS leukemic infiltration may represent points of reactivation points of reactivation of the disease even during the therapeutic remission.


[Frontal astrocytoma with spinal cord metastasis. Report of a case and review of the literature]. A case of a right frontal astrocytoma with spinal metastatic lesion in the region of the third dorsal vertebra is reported. The metastatic nodule was removed six months after the craniotomy. In the literature concerning to the dissemination of tumors cells is suggested that there is not a causal relationship between CSF seeding and operative intervention. Access to the ventricular system or basal cisterns is of primary importance in the production of metastases.


[Extensive cerebellar necrosis in sickle cell anemia. Report of a case]. A 6 month-old mulatto boy was admitted on account of acute gastroenteritis, malnutrition and dehydration. In the hospital, the child developed septicemia, and temperature reached up to 38.6 degrees C. Despite intensive antibiotic treatment the patient died 12 days after admission. Necropsy disclosed bilateral bronchopneumonia, bilateral fronto-parietal subarachnoid hemorrhage, and extensive necrosis of the inferior half of both cerebellar hemispheres. On histopathological examination of the necrotic cerebellar cortex, numerous sickled erythrocytes were observed in petechial hemorrhages, and, in lesser quantities, inside capillaries. Lesions of the central nervous system in sickle cell anemia most often involve the cerebral cortex, and a single extensive cerebellar infarction as present in this case seems extremely rare. The pathogenetic mechanism of the necrosis is unclear, since thrombosis was not observed either in large blood vessels or in capillaries. Possible contributory factors were the infectious condition (septicemia), fever, and anoxia caused by the extensive bronchopneumonia.


[Cysticercosis of the fourth ventricle simulating a posterior fossa neoplasm in cerebral scintillography. Report of a case]. The case of a twelve year old child with intracerebral hypertension and cerebellar syndrome in whom the neuroradiological and neurological examinations were suggestive of posterior cranial fossa tumor is reported. The brain scan depicted the scintigraphic pattern of midline neoplasms, most likely medulloblastoma or astrocytoma. At surgery a Cysticercus cellulosae was removed from the fourth ventricle. The authors suggest that in geographical areas with high prevalence of neurocysticercosis in the infantile population the hypothesis of the pseudotumoral form of the disease be remembered when one attempts to characterize the type of neoplasms of the posterior fossa as detected by brain scan.


Effect of high-intensity sound on cochlear microphonics and activity of inferior colliculus neurons in the guinea pig. The input-output functions of cochlear microphonics (recorded from the round window) in guinea pigs exposed briefly to high-intensity sound (2 kHz, 130 dB, 30 min) were shifted toward higher intensities by about 15 dB in comparison with normal animals. 2-4 h after the exposure this shift decreases to 10 dB. The response characteristics of the inferior colliculus neurons were compared under similar conditions. Thresholds at the characteristc frequencies (CF) measured 2-4 h after exposure, were raised by 30-50 dB, a higher threshold increase was observed at frequencies from 5-7 kHz. 48 h after exposure the thresholds approached those obtained in normal animals. There was no pronounced hair cell loss after exposure. It is assumed that in addition to the impairment of sound transduction in hair cells there may be a specific effect of high-intensity sound exposure on neuronal transmission in the auditory pathway.


[Light and electron microscopic studies of the greater epithelial ridge and its relationship to the developing tectorial membrane in the cochlear duct of the guinea pig (author's transl)]. In early stages of fetal development (36th day, 3rd turn) the thickening of the epithelium at the basal side of the cochlear duct forms two ridges. Later in fetal development the laterally situated lesser epithelial ridge forms the major part of the organ of Corti, whereas the medially situated greater epithelial ridge contributes only a small part to this organ. The medial part of the greater ridge consists of the columnar inner supporting cells, which bear a border of closely packed microvilli at their upper surface. Up to the time of the opening of the internal spiral sulcus in the 48th day of fetal development, there is a close spacial relationship between microvilli and filaments of the tectorial membrane. We conclude that the inner supporting cells contribute to the formation of the tectorial membrane. However, thus far we cannot entirely exclude a different possibility, that the inner supporting cells absorb material of the tectorial membrane. During the opening of the sulcus spiralis internus the inner supporting cells become considerably smaller, some of them undergo complete destruction by cytolysis, with pyknosis and karyorrhexis.


[Digital filtering of acoustical evoked potentials]. For better analysis of ERA-potentials it is necessary to eliminate disturbing frequencies by a smoothing filter. For this we propose a special optimized digital filter, which is applicable without falsification of form and amplitude of potentials. Its efficiency will be compared with other smoothing techniques.


10 years of experience with intratympanally applied streptomycin (gentamycin) in the therapy of Morbus Menière. During the last 10 years a total of 83 patients with severe cases of unilateral Morbus Menière were treated in our clinic. The proposed therapy was to administer streptomycin (gentamycinsulfate) intratympanically by applying two different ways of procedure. In the first group of 40 patients we attempted to destroy the vestibular organ without harming the cochlea whereby we avoided surgical intervention. In the second group of 43 patients we integrated more recent findings in the pathophysiological mechanism underlying the pathogenesis of Morbus Menière into our therapeutic considerations and attempted to exclusively destroy the secretorial epithelium with minimal dosages of aminoclycoside antibiotics. The results after treatment were clearly better for the second group of patients.


[Microphonic potentials in guinea pigs with liver damages]. In guinea pigs we produced certain histological liver damage. By 16 guic results of 16 guinea pigs without liver damage. The microphonic potentials of liverdamage animals was lower about 3.4 dB than potentials of healthy animals. Experimence in animals confirmed the hearingloss of inner ear and also pathological adaption by patients with chronic liver parenchym damage.


Electron microscopical and histochemical studies of outer hair cells in normal rabbits. The outer hair cells of the rabbit were electron microscopically and histochemically investigated. The results clearly showed that the outer hair cells of the rabbit have no agglomeration of mitochondria in its infranuclear region. This anatomical fact means that the functional mechanism in the outer hair cells of the rabbit may be substantially different from that of other animals which have agglomeration of mitochondria. From the results of the histochemical study, it is reasonably supposed that the anaerobic energy metabolism may ordinarily play the leading part in sustaining the cellular functions in the infranuclear region of the outer hair cells of the rabbit.


Respiratory quotient of stria vascularis of guinea pig in vitro. The respiratory quotient of the stria vascularis was measured in vitro by means of Cartesian diver microgasometry. A value of about 1.2 was found when the incubation medium was phosphate-buffered serum substitute with glucose as the sole substrate. This value suggests that endogenous lipids and amino acids do not contribute significantly to strial respiratory metabolism and that carbohydrate is the primary fuel in vitro. A high activity of the hexose monophosphate pathway may be responsible for raising the respiroatyr quotient above unity.


A correction and extension of the acetylated amino terminal sequence of ovalbumin. The acetylpeptides derived from S-carboxymethylovalbumin by cyanogen bromide and chymotrypsin have been isolated and shown by enzyme digestion and the dansyl-Edman method to fit the sequence acetyl-Gly-Ser-Ile-Gly-Ala-Ala-Ser-Met-Glu-Phe. This corrects the order of the third and fourth residues in the five-residue sequence given by Narita and Ishii [J. Biochem. (Tokyo), 1962, 52, 367--73]. The overlap of the C-terminal sequence of this extended sequence with the six-residue N-terminal sequence surrounding a half-cystine residue in ovalbumin gives the N-terminal sequence for ovalbumin as acetyl-Gly-Ser-Ile-Gly-Ala-Ala-Ser-Met-Glu-Phe-Cys-Phe-Asp-Val-Phe-Lys with residue 11 a cysteine residue.


Uptake of n-(9-anthroyloxy) fatty acid fluorescent probes into lipid bilayers. A description in thermodynamic terms is given of ligand-membrane interaction which may occur by either or both a binding and a partition process. Results obtained by fluorescence enhancement and polarization techniques on the uptake of n-(9-anthroyloxy) fatty acids by phospholipid bilayers are analysed to show that binding rather than partition effects primarily determine the extent of probe uptake. Liposome concentration-dependence effects are also reported which required that binding results obtained with different probes be compared at fixed lipid concentrations. On this basis it is concluded that as the separation of the anthracene and carboxyl groups within the fatty acid molecule is increased, and hence as the anthracene group moves deeper into the bilayer, the fluorescent probe is bound to the bilayer with greater affinity but is accepted by fewer binding sites within the membrane. Studies on probe uptake at high ionic strength and into negatively charged bilayers indicate that hydrophobic rather than electrostatic interactions make the dominant contribution to the free energy of binding.


Ultrastructural development of adipose tissue in foetal sheep. The development of subcutaneous and perirenal adipose tissue in foetal sheep of 40--150 days conceptual age was examined using electromicroscopy. Adipose tissue from both sites developed from pre-adipose cells of similar appearance, with few mitochondria, and commenced accumulating  lipid on about day 70 of gestation. In the perirenal fat there was marked proliferation of mitochondria between days 80 and 90 and the tissue developed into brown fat, cell profiles being characterized by many mitochondria with numerous distinct cristae, whereas in the subcutaneous cells which developed into white adipose tissue few mitochondria with fewer cristae were observed. Multilocular and unilocular cells occurred in both tissues near term. Nerves were first seen between brown adipose cells in a 130-day-old foetus and were frequently seen in older foetuses, but very few nerves were seen in the white adipose tissue. In hypophysectomized foetuses, either full- or post-term, the subcutaneous fat and internal fat were shown to be white and brown adipose tissue respectively, as in normal foetuses, although in one 164-day-old foetus the perirenal tissue appeared to be a mixture of brown and white fat.


A receptor assay for somatomedin-like activity using multiplication-stimulating activity (MSA) as radioligand. Multiplication-stimulating activity (MSA) in the medium of cultured rat liver cells was purified 120-fold by chromatography on Dowex 50W and Sephadex G 50. MSA was labelled with 125I-iodine and bound to a human placental membrane receptor. An assay for somatomedin-like receptor activity (SmLRA) in unextracted serum was based on the displacement of 125I-MSA from the placental receptor. The mean lambda (precision) was 0.063, sensitivity was less than 0.006 SmLRA units and interassay variation was 18%. The mean (+/- S.D.) SmLRA concentrations in 13 normal subjects, 7 growth hormone deficient patients and 8 patients with active acromegaly were 0.86 +/- 0.19, 0.34 +/- 0.08 and 2.34 +/- 0.82 U/ml, respectively. This assay may have potential clinical application in disorders of growth hormone secretion.


Haemoglobins in cattle and buffalo. Haemoglobin types of Bos taurus, Bos indicus, Bos banteng and Bubalis bubalis in northern Australia. The frequency of haemoglobin types in several major breeds of cattle in northern Austrailia was determined. In all Boss taurus cattle examined only the three common bovine haemoglobin types (AA, AB, BB) were found. F2 Africander cross-breeds showed only AA patterns. The frequency of haemoglobin B was significantly higher in Bos indicus type cattle than in Bos taurus breeds. In the pure breed Banteng cattle (Bos banteng) three genotypes (BB, CB, CC) were present. The eleven buffaloes types each showed two haemoglobins (A1 and A2) in proporotions of 71 to 29 respectively.


Tumor immunity to murine plasma cell tumours. Influence of responder genotype on the specificity of the immune response to plasmacytomas and T lymphomas. A tumour-associated antigen has been identified which is expressed on both BALB/c plasmacytomas and T lymphomas, but which does not induce a detectable cell-mediated immune response in the strain of origin of the tumours. The (BALB/c x C57BL) F1 hybrid, however, makes a readily detectable response both in vivo and in vitro in vitro experiments with various BALB/c H-2 F1 cogenic mice indicated that the genetic control of the response was not H-2 linked, and was associated with other C57BL genes.


Effect of mannitol on sodium retention during whole-gut perfusion. To undergo whole-gut perfusion, normal Chinese subjects drank an isotonic saline solution at a rate of 40 ml/min for 3-6 h. In spite of a diuresis, expansion of the extracellular fluid was evidenced by an increase of body weight and a decrease of haematocrit and plasma specific gravity at the end of perfusion. This fluid expansion resulted from sodium retention at a rate of about 140 mmole/h. When the NaCl of the perfusion solution was gradually replaced by isomotic amounts of mannitol, sodium retention was gradually reduced. Addition to the perfusion solution of up to 144-152 millimolar mannitol reduced the sodium retention rate to 6.5 mmole/h and thus prevented fluid expansion. We found that the sodium retention rate was inversely related to the difference between sodium concentration in the plasma and that in the perfusion solution. Thus, our results suggest that addition of mannitol with a decrease of sodium concentration in the perfusion solution creates a sodium concentration gradient between plasma and intestinal lumen which is unfavourable for intestinal absorption of sodium.


Factors influencing lipoprotein lipase activity in choline deficiency. Subcutaneous injections of the lipotropic agent, ethyl trichloracetate, to rats with established choline deficiency raised their plasma triglycerides by 60% and completely removed the hyperglyceridaemic response of Triton WR 1339. The plasma triglyceride levels of choline-supplemented rats were depressed slightly by ethyl trichloracetate administration, which was effective in abolishing response to Triton WR 1339. Lipoprotein lipase activity of epididymal fat pad was stimulated 60% while plasma lipoprotein was not stimulated by ethyl trichloracetate. The increased peripheral removal of low-density lipoprotein-triglyceride complex, allowing greater use to be made of existing apo-proteins, may explain the lipotropic character of the ester.


Alpha tocopherol and blood pressure in PN/n mice. The tail cuff blood pressure of PN/n mice, previously studied for arteritis and glomerulitis, was found to be raised before histological changes appeared. The pressure of mice bred for two generations on a diet containing a low level of alpha tocopherol (E) fell to that of control CBA mice. Replacement of E in the diet, or by intraperitoneal injection, led to a rise of pressure. The pressure reached a mean of 150 mm/Hg after breeding the mice for a further three generations on a more complete diet with additional E. An inhibitory effect of E on prostaglandin production was postulated. E had no effect on the pressure of CBA/MAC mice.


A technique for glottic reconstruction following vertical partial laryngectomy. In order to obtain a good phonatory function by glottic reconstruction following vertical partial laryngectomy, the following basic conditions should be satisfied: (1) adequate glottic closure should occur during phonation; (2) the top of the bulge constructed on the operated side should be located at the level of the vocal fold in order to prevent ventricular fold vibration; and (3) the surface of the bulge should be smooth. A technique for glottic reconstruction which appears to meet these requirements is described. The sternohyoid muscle is dissected at the requirements is described. The sternohyoid muscle is dissected at the level 5 cm below the vocal fold, and the upper portion is used as a single pedicled flap. The muscle flap is bent approximately 90 degrees at the level of the upper border of the cricoid cartilage and inserted into the intralaryngeal wound so as to make a large bulge. The muscle flap is covered by hypopharyngeal mucosa or a free graft of lip mucosa.


Extramedullary plasmacytoma of the oropharynx producing kappa-type Bence-Jonas protein. A case of extramedullary plasmacytoma in the oropharynx of a 41 year-old woman is reported. Histologically, the tumor was plasmacytoma consisting mainly of matured plasma cells and showing a deposit of amyloid in the interstitial structure. Immunoelectrophoretic studies of the concentrated urine specimen revealed a kappa-type Bence-Jones protein even though there was no increase in blood M-protein. Lineac electron radiation of 5,100 rad was given over a period of eight weeks but no effect was noted. After the tumor was surgically removed, follow up of the patient was made for 2 years without evidence of recurrence or metastasis.


Identification and properties of UDP-glucose: cyanidin-3-O-glucosyltransferase isolated from petals of the red campion (Silene dioica). An enzyme catalyzing the transfer of the glucosyl moiety of UDP-glucose to the 3-hydroxyl group of cyanidin has been demonstrated in petal extracts of Silene dioica mutants with cyanidin-3-O-glucoside in the petals. This transferase activity was also present in young rosette leaves and calyces of these plants. The highest glucosyltransferase activity was found in petals of opening flowers of young plants. The enzyme was purified ninetyfold by PVP and Sephadex chromatography. The glucosyltransferase had a pH optimum of 7.5, had a "true Km value" of 4.1 x 10(-4) M for UDP-glucose and 0.4 x 10(-4) M for cyanidin chloride, and was not stimulated by divalent metal ions. Both p-chloromercuribenzoate and HgCl2 inhibited the enzyme activity. Pelargonidin chloride and delphinidin chloride at reduced rates also served as substrates. The enzyme did not catalyze the glucosylation of the 3-hydroxyl group of flavonols or the 5-hydroxyl group of anthocyanins. ADP-glucose could not serve as a glucosyl donor. The results of Sephadex G150 chromatography suggest that the glucosyltransferase can exist as dimer of about 125,000 daltons and as active monomers of 60,000 daltons. The genetic control of the glucosyltransferase activity is discussed.


Identification, properties, and genetic control of UDP-glucose: cyanidin-3-rhamnosyl-(1 leads to 6)-glucoside-5-O-glucosyltransferase isolated from petals of the red campion (Silene dioica). An enzyme catalyzing the transfer of the glucosyl moiety of UDP-glucose to the 5-hydroxyl group of cyanidin-3-rhamnosyl-(1 leads to 6)-glucoside has been demonstrated in petal extracts of Silene dioica plants. This glucosyltransferase activity was not detectable in green parts of these plants. The enzyme activity is controlled by a single dominant gene M; no glucosyltransferase activity could be demonstrated in petals of m/m plants. The enzyme was purified eightyfold by PVP and Sephadex G50 chromatography. The glucosyltransferase had a pH optimum of 7.4, had a molecular weight of about 55,000, was stimulated by divalent metal ions, and had a "true Km" values of 0.5 x 10(-3) M for UDP-glucose and 3.6 x 10(-3) M for cyanidin-3-rhamnosylglucoside. Pelargonidin-3-rhamnosylglucoside also could serve as acceptor. The enzyme did not catalyze the glucosylation of the 5-hydroxyl group of cyanidin-3-glucoside, although in petals of M/- n/n mutants cyanidin-3,5-diglucoside is present. ADP-glucose could not serve as a glucosyl donor.


Acetylation of sulfamethazine in a Nigerian population. Sulfamethazine (syn, sulfadimidine) is inactivated by conversion to its N-acetyl derivative. Individuals are phenotyped as either "rapid" or "slow" acetylators. We have tested the validity of this theory in a Nigerian population. The frequency distribution histograms of the percentage acetylsulfamethazine in urine and serum were found to be bimodal, indicating the existence of a genetic polymorphism as observed by earlier workers. A plot of the percentage of the drug acetylated in serum against that in urine of the same individual results in a satisfactory separation of the rapid and slow acetylator phenotypes. An incidence of the slow acetylator phenotype of 41% was observed in the Nigerian population tested. How this observation fits into the hypothesis that the slow frequency of the allele increases from the Arctic Circle toward the Equator is discussed.


Esterase 13, a new mouse esterase locus with recessive expression and its genetic location on chromosome 9. A new esterase locus (Es-13) has been identified in Musculus. Strains AEJ/GnRk, LG/J, SJL/J, and SWR/J carry a recessive allele, Es-13b, for a locus possibly involved in the posttranslational modification of a kidney esterase. All other strains observed carried the dominant Es-13a allele. Es-13 was mapped on Chr 9 by recombinant inbred lines and by conventional backcrossing experiments. Backcross data produced the following gene order and map distances: Lap-1 (31.6 +/- 7.5 cM) Es-13 (2.6 +/- 2.6 cM) Mod-1.


Xanthommatin biosynthesis in wild-type and mutant strains of the Australian sheep blowfly Lucilia cuprina. The synthesis of eye pigments has been studied in the seven eye color mutants of the Australian sheep blowfly, Lucilia cuprina. Six appears to be affected primarily in the synthesis of xanthommatin. In wild type, the onset of xanthommatin biosynthesis occurs midway through metamorphosis. Developmental patterns of accumulation of the xanthommatin precursors tryptophan, kynurenine, and 3-hydroxykynurenine have also been established for wild type. By determining the levels of these precursors in late pupae of the mutants, it has been shown that the mutant yellowish accumulates excess tryptophan and the mutant yellow accumulates excess kynurenine. The implications of these results--that yellowish lacks tryptophan oxygenase, thus failing to convert tryptophan to kynurenine, and that yellow lacks kynurenine hydroxylase (blockade in the conversion of kynurenine to 3-hydroxykynurenine)--have been confirmed. This has involved in vitro assays of tryphophan oxygenase and precursor feeding experiments. The precursor accumulation patterns are less clear for the other mutants.


Variation in the genetic structure of Peromyscus populations. I. Genetic heterozygosity--its relationship to adaptive divergence. The genetic structure of nine Peromyscus maniculatus nebrascensis demes from southeastern Wyoming was determined by analyzing allozymes encoded by 23 genetic loci with polyacrylamide gel electrophoresis. Genetic variability is extremely high for two genetic parameters; the proportion of loci polymorphic per deme averaged 0.41. Previous estimates of genetic heterozygosity for species within the genus Peromyscus have a mean of 0.06. The results of the present study suggest that genetic heterozygosity is considerably higher within P. maniculatus demes than within demes of other species in the genus. Geographic range is correlated with heterozygosity among Peromyscus species, as is adaptive divergence into broad-niched species. These correlates suggest that high heterozygosity may reflect an adaptation to a variable environment.


The V gamma chain of fetal hemoglobin of the orangutan. Previous studies suggested that orangutans have nonallelic structural genes for their gamma chains, because either a threonyl or an alanyl residue may occupy position 135. Further investigation has now detected that position 75 may have either an isoleucyl or a valyl residue. From available evidence, the isoleucyl and threonyl residues are in one chain an the valyl and alanyl in the other. Orangutans appear to be homozygous for the two types of nonallelic genes.


Genetics and ontogeny of aldehyde dehydrogenase isozymes in the mouse: localization of Ahd-1 encoding the mitochondrial isozyme on chromosome 4. Electrophoretic variants for the mitochondrial isozyme of aldehyde dehydrogenase (AHD) have been observed in inbred strains and in Harwell linkage testing stocks of Mus musculus. F1 (LVC X C57BL/Go) mice showed a codominant allele three-bounded phenotype, which suggests a dimeric subunit structure (designated AHD-A2). The anodal-migrating supernatant isozyme of AHD was electrophoretically invariant among the 23 inbred strains and stocks examined. The genetic locus encoding AHD-A2 (suggested name Ahd-1) is localized on chromosome 4 and was mapped close to je (jerker) and Gpd-1 (encoding the liver and kidney isoenzyme of glucose-6-phosphate dehydrogenase). Ontogenetic analyses demonstrated that both AHD isozymes exhibited low activity in late fetal and early neonatal liver and kidney extracts, and reached adult levels within 3 weeks of birth.


Genetic variation in the activity of the histidine catabolic enzymes between inbred strains of mice: a structural locus for a cytosol histidine aminotransferase isozyme (Hat-1). Variation in activity of the main histidine catabolic enzymes (histidase, urocanase, and aminotransferase) has been surveyed using inbred strains of mice (C57BL, DBA, Peru, SM, and SWR). Some variation was found in the activity of all enzymes, but only in the case of cytosolic histidine aminotransferase was it greater than twofold (SM 3.3-fold greater than C57BL). The divergent strains for the activity of this enzyme were crossed and the F1's were backcrossed; the segregation analysis indicated a single locus with additively acting alleles (designated Hat-1: a allele SM, b allele C57BL). Cytosolic histidine aminotransferase differed in heat stability between SM and C57BL, indicating that Hat-1 is a structural locus. The conflict in the biochemical literature (Morris et al., 1973; Noguchi et al., 1976a,b) over the number and subcellular distribution of the histidine aminotransferase isozymes is partly resolved by the acquisition of a variant at the Hat-1 locus. Hat-1 affects the cytosolic form but not the mitochondrial form of the enzyme. Purification and analysis of the isozymes of histidine aminotransferase from livers of C57BL and SM mice will further clarify the situation.


[Plasma renin activity in hypertensive patients under basal conditions and in various postures: preliminary data]. We have studied PRA levels in 10 healthy subjects compared with 10 patients affected with essential hypertension (with low PRA) on venous blood samples collected after 8 hours of rest and after 15-20 minutes of slow plain walk. Contemporarely we have taken up arterious pression levels in each class of subjects of these studies. No significant differences of PRA are demonstrable in healthy subjects and in patients affected with essential hypertension. Postural changes in hypertension produces significant rise of PRA, not related to arterial pressure.


[Oxoprenolol and plasmatic renin activity in essential hypertension: preliminary data]. We have studied PRA levels in 10 healthy subjects compared with 10 patients affected with essential hypertension (with low PRA) on venous blood samples collected after 8 hours of rest and after 15-20 minutes of slow plain walk and 15 minutes after intravenous administration of oxoprenolol (mg 2). Contemporarely we have taken up arterious pression levels in each class of subjects of these studies. Postural changes produces significant rise of PRA in subjects affected with essential hypertension, that is significantly inhibited by pharmacologic interference produced by beta-blocking agents. This occurrence is independent of arterial pressure changes.


[Incorporation of S-adenosylmethionine in the isolated and perfused rat liver. Preliminary study]. The uptake of labeled S-adenosylmethionine (SAM) by isolated and perfused rat liver has been compared to that of methionine: the rate of incorporation of the amino acid exceeds by about three times that of the sulfonium compound. S-Adenosylmethionine transport system shows saturation kinetics with an apparent Km of 59,5 microM and is energy-dependent, as demonstrated by the inhibition by 2,4-dinitrophenol.


[Study of circadian variations of plasma renin activity in the normal human in the supine position]. A study of circadian variations of plasma renin activity in normal supine man.--The cosinor analysis has detected circadian rhythm of PRA in fifteen normal supine men, aged 21-28, studied over a 24-hour span. The acrophase occurs at 05.55 and it is consistent with the findings of the other authors.


[Effect of anti-inflammatory drugs on the motility of human polymorphonuclear granulocytes]. Polymorphonuclear leucocytes play an important role in the inflammatory process, and their functions are likely to be regulated by pharmacological agents. In this paper we report the "in vitro" effect of non steroidal anti-inflammatory drugs on random and chemotactic motility of human leucocytes, and demonstrate that the two forms of movement, spontaneous and directional, are differently inhibited by low concentrations of these agents. Leucocytes of patients with recurrent inflammation are unaffected by these drugs.


Changes in the lung alveolar proteins in some experimental conditions. The Authors have directed their research to the alveolar lining (the surfactant) proteins and they have particularly studied its alterations in shock pathological conditions. Some rats have been subjected to haemorrhagic and toxic shock, by Escherichia Coli's lipopolysaccharide; then lung washing has been performed and on extracted liquid proteins have been studied by two-dimensional immunoelectrophoresis (TDI). The obtained data have been encouraging and very useful for studies process.


The proteins of the lung alveolar lining. The protein composition of the lung washing has been analysed by immunochemical methods: it has been possible to demonstrate the presence of many proteins, mainly albumin, immunoglobulins and beta-globulins, some of them seem laying in the alveolar lining and having the function of stabilizing the surfactant system.


Responses of the intestine of the giant African snail (Achatina fulica) to acetylcholine in Meng's solution with low sodium, potassium and calcium ions. Decreasing the concentration of sodium in Meng's solution produced a non-parallel shift of the dose-response of acetylcholine on the intestine of the Giant African Snail Achatina fulica. This decrease in sodium decreases the sensitivity of the tissue to acetylcholine and sensitivity was not restored with several washings. The response to decrease calcium is very similar to that of sodium. In the case of potassium however 10% K+ produced less depression in sensitivity than 25% which even caused less depression of sensitivity compared with 50% potassium. The results show an abundance of spare receptors.


Relation between haemolymph proteins and fat body during metamorphosis in Danais chrysippus Linn. II. Changes in haemolymph protein fractions and histology, of adipose tissue has been observed in the larvae, pupae and newly emerged adults of Danais chrysippus. At time of pupation, proteins get accumulated in the fat body and in turn are utilized in metabolic process occuring during metamorphosis. A clear correlation exists between the adipose tissue and haemolymph proteins. A human-serum-albumine like proteins was not observed in this insect species.


Hematologic and hemopoietic alterations following experimental benzene exposure in newts (Triturus cristatus). Changes in the hematological picture in newts have been investigated utilizing benzene exposure. The first deviation occurs in circulating white cells that become more numerous. Subsequently there is an increase of immature cells on the cortical zone of the liver. About two weeks after the first treatments a decrease of circulating leukocytes begins and the immature white cells continue to increase both in circulation and in the cortical zone of the liver. The red  cells present a decrease after one month of treatment. This is preceeded by a decrease in hemoglobin percentage and an increase in the size of red cells and in the number of immature red cells. The data concerning animals treated with an hemolytic agent and with benzene demonstrates an early action of benzene also on red cells. The results suggest a maturation in capacity caused by benzene in both white and in red cells. The intensity of alteration seems proportional to the frequency of treatments. The onset of a particular modification, however, is related to the time interval following the first treatment.


Transitory colour-change mechanism in a fresh-water teleost, Clarias batrachus (L). The rate of colour change in the fish Clarias batrachus (L.) has been studied as a response from black to white background and vice versa. The 'Derived Ostwald Index (D.O.I.)' method proposed by Healey (1967) has been used to measure the melanophore responses of the fish. Observations show that the fish is quite sensitive to background responses. The rate of colour change is fast. The colour change is quite rapid in both, the paling and the darkening experiments in the beginning as compared to the later stages which are slow and gradual. The results indicate that the process of colour change is mainly under nervous control in the initial stages while in the later stages the chromatic response seems to be regulated mainly by hormone(s). The fish is better adapted on a white background (maximum paling 1.7 grades of D.O.I. scale in 10 hours) than on a black background (maximum darkening 6.35 grades of D.O.I. scale in 20 hours). It is suggested that chromatic control mechanisms in the fish include the sympathetic pigment-aggregating fibres constituting the nervous control and at least a pituitary principle, the melanophore-aggregating hormone (MAH) constituting the hormonal control.


Biofeedback in the treatment of gastrointestinal disorders. A wide range of secretory (salivation, gastric acid and bile secretion) and motor functions (rumination, esophageal and anal sphincter contraction, gastric and colonic motility) have been successfully modified using operant conditioning procedures or biofeedback training. The clinical syndromes to which these studies have been addressed include rumination, reflux esophagitis, hypersecretion of acid associated with peptic ulcer, irritable bowel syndrome, and fecal incontinence. The available evidence strongly suggests that biofeedback is effective and is the treatment of choice for some types of fecal incontinence, and the evidence supports the effectiveness of operant conditioning for the treatment of intractable rumination in infants or retarded individuals. There is suggestive evidence that a nonspecific biofeedback technique, EMG biofeedback for skeletal muscle relaxation, may contribute to the healing of peptic ulcers, but the data are so far inconclusive. Biofeedback approaches to the treatment of other clinical syndromes are at the investigational stage only, and no predictions can be made regarding their efficacy.


Problems of science in the development of cotton growing in the USSR. This article considers the development of cotton growing in the USSR as one of the leading branches of agriculture. The production of raw cotton and the yield of cultivated varieties of cotton reached a high level. Further increase in yield and increase in production of raw cotton are accompanied by the need to resolve a number of problems. In resolving them, a leading role will be played by science. The author enumerates the principal problems to which efforts of scientific-research institutions will have to be addressed.


Prospects for developing and improving a chemical method of pest control in the next 10 to 15 years. The assortment of chemical substances for pest control which exists in the world or is planned by us, and the reserves which exist in scientific research make it possible to assert that: 1) It is possible to produce an assortment of pesticides that is practically harmless for man and useful animals; 2) it is possible to eliminate the accumulation of pesticides and their residue in the environment, in food products, and in food chains; 3) it is possible to produce highly selective pesticides which will not damage useful inhabitants of the biosphere, particularly useful arthropods and soil microorganisms; 4) it is possible with the proper technical approaches, especially with proper alternation of pesticides, to avoid the development of resistant strains of pests. This requires continuation of intensive scientific and technical investigations both of the pesticides themselves and in producing integrated systems with the use of an entire complex of means and methods for protecting the harvest, and improving the technical means of application.


Ability of free-living nodule bacteria to fix atmospheric nitrogen. Literature material is presented on the ability of free-living nodule bacteria for asymbiotic nitrogen fixation, detected for the first time in 1975. Necessary components of the nutrient medium in the use of which the nitrogen-fixing ability of rhizobia in pure cultures is manifested, proved to be sugars and intermediates of the citric acid cycle, as well as small quantities of bound nitrogen. The experimental data available in the literature are evidence of the presence of a complete assortment of genes for the synthesis of the nitrogenase enzyme complex in free-living nodule bacteria.


Quantitative cytochemistry of glycogen in cells of pea and lupine nodule bacteria. Using a fluorescent variation of the method of PAS reaction with auramine OO-SO2, the content of PAS-positive substance, identified on the basis of supplementary treatments of the preparations with alpha-amylase and a hot mixture of chloroform with methanol and glycogen, was determined cytofluorimetrically in cells of effective and ineffective strains of lupine and pea nodule bacteria in pure culture and under conditions of symbiosis. The largest level of glycogen was detected in bacteroid forms from lupine nodules and especially those of the pea after inoculation with ineffective strains: in comparison with the bacteroids from nodules of effective bean-Rhizobium symbiosis, it was 2.5--3.0 times as high. Cytofluorimetric determination of glycogen in cells of nodule bacteria, especially under conditions of symbiosis, can be considered as an indirect criterion of effectiveness in the preliminary selection of strains.


Metabolism of [14C]nicotine in wild species of Nicotiana. Nicotine metabolism was studied in a number of wild species of the genus Nicotiana. It was shown that exogenous alkaloid, labeled with 14C on the methyl, as well as in each of the heterocycles individually, when introduced into the above-ground organs of these species during the period of their vegetative development, is actively metabolized. It was established that as a result of the conversions of exogenous nicotine, anabasine is formed in anabasine species of the genus Nicotiana, while nornicotine is formed in nornicotine and certain nicotine species. It can be assumed that the low content of alkaloids in wild species of the genus Nicotiana is due to the fact that the ability of these species to metabolize the indicated compounds is considerably more pronounced than in cultivated tobaccos.


Organic phosphorus of the soil and its mineralization. The question of the composition of organic phosphorus in soil and pathways of its mineralization is discussed. The literature data and the author's own results on the content of polyphosphates in microorganisms and in soil are cited. Possible ways of studying the accessibility of soil factors depending on the composition of the microflora and degree of polymerization of immobilized inorganic polyphosphates are discussed.


Method of determining the amino acid composition of plant samples and separation of proteins into fractions with buffer solutions. In the proposed method, the determination of the amount and amino acid composition of extractable and inextractable proteins, nonprotein nitrogen, and free amino acids is performed in one analytical sample. The above-mentioned nitrogenous substances are extracted with borate buffer. Shortened and expanded schemes of separation of proteins into fractions using buffer solutions are given. For the shortened schemes of analysis, the proteins are separated into readily soluble, medium soluble, sparingly soluble, and insoluble fractions, and in the expanded scheme into eight fractions: three fractions of readily soluble proteins, two fractions each of medium- and sparingly-soluble proteins, and insoluble proteins.


Methods of utilization of regularities in modificational variability of quantitative characters in plant breeding. The nature of the modificational and genotypic variability of 30 quantitative characters in wheat varieties with different numbers of genes for dwarfing, and nine characters in contrasting pea varieties, differing in leaf type, was investigated. The experimental data, obtained in 1971--1974 and analyzed in the M-220M and Minsk-22 computers, showed a high degree of similarity in the modificational variability of similar quantitative characters for all varieties of the same crop. Significant similarities were also found in the modificational variability of identical quantitative characters for the two species (wheat and peas), which showed that the regularities in modificational variability are generally applicable in biology. The coefficients of variation, calculated from the total data obtained, for modificational (CVm), genotypic (CVg) and overall modificational-genotypic (CVm+g) variability, for the different quantitative characters, may be useful criteria in plant breeding. They may reveal genotypic differences in the quantitative characters in hybrids and mutant populations, and may thus be useful in improving the efficiency of selection of wheat and pea strains.


Production of Staphylococcus membranes and their enzymatic and protein characteristics. Three methods of decomposition of Staphylococcus aureus 209-P cells were compared for the production of membranes-ultrasound, a press, and enzymatic lysis. All the tested methods permitted the isolation of enzymatically active membranes, differing somewhat in protein composition.


Cumulative effect in microwave irradiation. In experiments on 853 nonpedigreed mice a study was made of the cumulative effect of microwave irradiation using the lethal effect as a criterion. It was demonstrated that there is a correlation between the coefficient of accumulation and conditions of irradiation.


Metabolism of nucleic acids in hepatomas with a different degree of differentiation. A comparative study was made of the metabolism of nucleic acids in hepatomas with a different degree of differentiation (46, 60, and 22A), liver, and regenerating liver. A direct correlation was found between the initial rate of incorporation of [14C]thymidine into DNA and the maximum growth rate of the hepatomas and regenerating liver. An increase of the specific DNA content as the hepatomas deviated from the normal liver is shown. A direct relation was found between the value of the RNA/DNA ratio and maximum growth rate of the hepatomas. A study of the catabolism of nucleic acids revealed inhibition of the breakdown of nucleic acids of hepatomas in comparison with a number of normal tissues, except liver tissues. The possible cause of these phenomena are discussed.


Synthesis of aminoacyl adenylates and their role in abiogenic peptide synthesis. Preparative synthesis of adenylates of amino acids with modifications of Meister's method, pertaining to the purification and identification of the reaction products, is described. The significance of the synthesized substances is discussed in connection with the problem of abiogenic synthesis of peptides.


Influence of serotonin on calcium transport in rat liver mitochondria. It was shown in experiments in vitro that serotonin, depending on the concentration, has different effects on calcium transport in rat liver mitochondria. In a concentration of 10(-6) M it increases the ability of the mitochondria to bind calcium; in a higher concentration (10(-4) M) serotonin accelerates the release of calcium from the mitochondria. The effect of serotonin is detected at a calcium concentration in sucrose medium of the order of 10(-4) M and is not observed when the mitochondria are incubated in a complete reaction medium.


Glycosides during ensiling.

Glycosides during ensiling. The content of glycosinolates in crucifers and other plants and their behavior during ensiling was studied. It was found that up to 80% of glycosinolates decompose during ensiling. Acidification of the mass with formic acid somewhat slows down the decomposition of glycosinolates. Decomposition of glycosinolates does not occur during ensiling of clover, which, in the authors' opinion, is explained by the low activity of glycosinolate hydrolases. The evolution of hydrogen sulfide at the start of ensiling of a number of crops was established.


Effect of a strong magnetostatic field on proliferation of duodenal epithelial cells in mice. The proliferative activity of duodenal epithelial cells in mice subjected to the effect of a 1000-Oe magnetostatic field (MSF) was studied. It was established that the one-day effect of a strong MSF causes transient disturbance of cell division processes. This is indicated by changes in the mitotic index and content of cells in the duodenal crypt, and also by the increase in the number of pathological forms of mitoses with a predominance of chromosomal damages.


cis-Dichlorodiammineplatinum(II) and adriamycin treatment of advanced ovarian cancer. Treatment with a combination of adriamycin (ADM) and cis-dichlorodiammineplatinum(II) (DDP) has been evaluated in 24 patients with advanced ovarian cancer. Twenty patients had received prior chemotherapy and/or radiation therapy. Objective remissions were seen in ten patients. The usual toxic manifestations of ADM and DDP were observed. It is concluded that the combination is effective therapy for ovarian cancer. Further investigation of this combination versus single agents is warranted.


Potential anticancer agents. XVII. New developments in the benzoic acid nitrogen mustards area. In order to obtain aromatic nitrogen mustards with improved therapeutic index against experimental neoplasms, greater than 75 new compounds were synthetized and studied. Their structure-activity relationship analysis led to the following conclusions: (a) the carboxylic group (especially when located in the meta position with respect to the nitrogen mustard group) exerts a favorable effect on the biologic properties of such compounds, probably by improving their transport characteristics; (b) a linear relationship was found between the chemical reactivity (expressed as alkylation rate, log k66) and toxicity (LD50) of 31 investigated compounds; and (c) the ortho effects also seem to be of importance in this area for a more accurate control of the nitrogen mustard activity. Other criteria (ie, log P, nucleophilicity of the target centers) involved in the rational design of aromatic nitrogen mustards are discussed. The design of new derivatives was oriented toward compounds which (a) were able to couple with selected proteins (ie, antibodies) leaving the cytotoxic moiety intact, and (b) were obtained by coupling of the 3-N,N-bis(2-chloroethyl)amino-4-methyl-benzoyl moiety with selected carriers (steroids, chromanones, etc) by way of an esteric bond.


Perturbed cell kinetics of 9L rat brain tumor cells following dianhydrogalactitol. Kinetic changes induced by dianhydrogalactitol (DAG) in cultured 9L rat brain tumor cells were studied using conventional autoradiography and flow cytometry. Cell cycle parameters for the untreated cell line were: G1, 8.5 hours; S, 8.2 hours; G2, 3.2 hours; M, 0.5 hour; and cell cycle time, 19.5--20 hours. Treatment with 5 micrograms/ml of DAG, which caused 89.8% cell kill as measured by the colony-forming efficiency assay, resulted in the following effects: (a) undisturbed progression of G2 cells toward mitosis; (b) disturbed progression of the cells in the S--G2 boundary; (c) extreme prolongation of DNA synthesis time; and (d) temporary accumulation in G2 phase of cells that were in G1 or S phase at the time of treatment.


Therapeutic potentiation of nitrosoureas using chlorpromazine and caffeine in the treatment of murine tumors. The therapeutic usefulness of chlorpromazine (CPZ) and caffeine (CAF) in combination with selected nitrosoureas was investigated in mice bearing L1210 leukemia, Lewis lung carcinoma, and B16 melanoma. We found that using BCNU with either CAF or CPZ was therapeutically superior to using either agent alone to treat mice bearing L1210 leukemia. Administering all three drugs in combination did not improve upon the therapeutic responses obtained with the two-drug combinations. In mice implanted with Lewis lung carcinoma or B16 melanoma, responses to treatment with the triple combination of methyl-CCNU, CAF, and CPZ suggested, but did not clearly establish, superiority over each two-drug combination or methyl-CCNU alone.


Positive phase II trial of dibromodulcitol in patients with metastatic melanoma refractory to DTIC and a nitrosourea. Twenty-five patients with measurable metastatic melanoma refractory to DTIC and a nitrosourea were treated with dibromodulcitol (DBD). DBD was administered orally at bedtime at a dose of 100 mg/m2/day until hematologic toxicity (a greater than or equal to 50% decrease in the wbc or platelet count) was induced. Five patients experienced clinically useful objective remissions; responding lesions included both soft tissue metastases and visceral metastatic disease. It is concluded that DBD is useful in the treatment of patients with metastatic melanoma and thus joins DTIC and the nitrosoureas as single agents which are active against this malignancy.


Phase II study of mitomycin C and vinblastine in women with advanced breast cancer refractory to standard cytotoxic therapy. The combination of mitomycin C and vinblastine in the dose and schedule used in this study (6 and 5 mg/m2, respectively, every 14 days) was of little clinical efficacy in the management of metastatic breast cancer already refractory to standard chemotherapy and hormonal therapeutic approaches.


Testing of 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) in mouse L1210 leukemia and 37 sarcoma. The antimetabolite 2,3-dihydro-1,3-6H-oxazine-dione (3-oxauracil) has been investigated in an attempt to elucidate its effects on survival time of DBA/2 and B6D2F1 mice with L1210 leukemia and of outbred albino mice with 37 sarcoma. A significant increase in survival time was observed in mice with 37 sarcoma and slight effects were observed in mice with L1210 leukemia when treated with 3 x 12.5 or 3 x 25 mg/kg of 3-oxauracil. No toxic side effects were observed when large therapeutic doses of the drug were given.


Ventricular overdrive suppression of idioventricular rhythm in patients with complete heart block. Idioventricular rate, QRS width, site of block and responses to ventricular overdrive pacing were studied in 29 patients with chronic complete heart block in an attempt to distinguish patients liable to syncopal attacks. Ten patients were asymptomatic, 5 gave a history of presyncope and 14 of syncope. Although the mean idioventricular rate of the 10 patients in the narrow QRS group (40.0 per min) was significantly faster than that of the 19 patients in the wide QRS group (35.5 per min; P less than 0.02), the rate did not distinguish symptomatic patients in either the narrow or the wide QRS groups. His bundle studies of the site of block were also unhelpful. Overdrive right ventricular pacing at increasing rates was used to assess ventricular escape times which were not significantly different in symptomatic and asymptomatic wide QRS patients. There was, however, a significant difference in the product of maximum ventricular escape time X overdrive cycle length between symptomatic and asymptomatic narrow QRS patients after 30 s overdrive (3.850+/-1.670 vs 1.070+/-0.475; P less than 0.01); 60 s overdrive (5.020+/-2.170 vs 1.240+/-0.515; P less than 0.01) and 120 s overdrive (6.040+/-2.900 vs 1.460+/-0.275; P less than 0.01) which may have clinical predictive values.


Synthesis of myosin heavy and light chains in the afterloaded guinea pig right ventricle. Increased afterload causes increased cardiac myosin synthesis and ultimately leads to hypertrophy. Since the latter is associated with altered myosin ATPase activity, it was of interest to study the synthesis of myosin subunits in the acute response to this stress. An in vitro guinea pig heart preparation was used which allowed application of afterload to the right ventricle with unaltered coronary flow, and also permitted measurement of synthesis of myosin heavy chains (HC) and combined light chains (LC) by continuous perfusion with labelled amino acids (3H-lysine and/or 3H-phenylalanine) of constant specific activity. Isolation of 3H-labelled HC and LC with heterologous unlabelled carrier was possible because of identical mobilities of HC's and LC's from unlabelled lamb carrier myosin and 3H-labelled guinea pig myosin. This permitted study of comparative synthesis of the HC and LC in small samples as the single guinea pig right ventricle (100--150 mg) and avoided errors inherent in pooling hearts or in measurement of turnover in the nonsteady state. After 3 h or perfusion, the ratio of synthesis of HC/LC was 2 : 1 in controls. This ratio increased significantly to 3 : 1 in after load. It is possible that the disproportionate increase in HC synthesis may lead to stoichiometric problems in myosin assembly which ultimately effect altered myosin ATPase activity.


Vibration-induced hyperresponsiveness of arterial smooth muscle to noradrenaline with special reference to Raynaud's phenomenon in vibration disease. Effects of in vitro and in vivo vibratory stimulations were studied on dose-response relationships of noradrenaline in excised femoral arteries of dogs and rats. The responsiveness of these arteries were enhanced after the application of the stimulation. The degree of the hyperresponsiveness was dependent upon frequency, amplitude, and duration of the stimulation. Based on the experimental results, a possible explanation was offered for Raynaud's phenomenon in vibration disease.


Morphological and topographical variations of the outlet chamber in complex congenital heart disease: an angiocardiographic study. The outlet chamber of the human heart can show considerable variations in its morphology and topography (relationship to main ventricular chamber), and such variations in anatomy and spacial relationship may be predictive of the associated intracardiac anatomy. Although there is considerable debate about whether the position of the outlet chamber is indicative of the type of bulboventricular loop (whether D- or L-), a right-sided and anterior outlet chamber has different implications than a left-sided, superior, and more posterior positioned one. The inflows into the outlet chamber can vary anatomically, and progressive changes in the calibers of these communications can adversely alter the natural history. One or both of the greak vessels, or neither, or a persistent truncus arteriosus can originate from the outlet chamber, and any significant morphological change in the outlet chamber may or may not adversely affect either the pulmonary or systemic blood supply, or both. Finally, any consideration of the outlet chamber raises important conceptual difference in terminologies. At present, there is not unanimity as to what constitutes either an outlet chamber (as compared to a "small right ventricle" in tricuspid atresia) or a single (primitive) ventricle. Any discussion of the morphological and topographical variations of the outlet chamber must be viewed with respect to the terminology employed.


Hemodynamic assessment of the new aortic Carpentier-Edwards bioprosthesis. Although glutaraldehyde-preserved porcine aortic Hancock heterografts have lower thromboembolism incidence than mechanical aortic valves, Hancock xenografts provide less functional aortic outflow orifices and thereby greater transvalvular gradients than mechanical prostheses. The newly developed aortic Carpentier-Edwards porcine heterografts comprise a thin-walled Elgiloy flexible metal stent covered with Teflon which provides somewhat wider internal orifices than aortic Hancock valves of the same external annulus diameter. Since aortic Carpentier-Edwards xenografts have not been clinically evaluated previously, the present study assessed cardiac function and heterograft performance (1.7 months postoperation) and clinical status (4.2 months postoperation) of 19 patients with severe aortic stenosis and/or regurgitation prior to surgery. Left ventricular end-diastolic pressures decreased (17 to 9 mm Hg), cardiac index remained normal, and clinical symptomatology diminished markedly. Mean peak transxenograft systolic pressure was only 16 mm Hg (valve area 1.73 cm2), without meaningful regurgitation. Thus aortic Carpentier-Edwards bioprostheses provide generally excellent heterograft function which appears more favorable than previous reports of Hancock xenografts.


Effects of dextran infusion on left ventricular volume and pressure in man. The purpose of this investigation was to quantitate the changes in left ventricular volume and end-diastolic pressure that occur with rapid infusion of 500 ml of low molecular weight dextran, and thus to study left ventricular pressure-volume relationships. Left ventricular pressure and echocardiographic dimensions were recorded before, during, and following dextran infusion in eight patients with normal left ventricular function. With the infusion of dextran, left ventricular end-diastolic pressure rose progressively from 10 +/- 3 mmHg (mean +/- SD) to 24 +/- 5 mmHg, whereas end-diastolic volume increased from 95 +/- 23 ml to 118 +/- 26 ml (24%). These results serve to emphasize the steepness of the left ventricular pressure-volume relationship at end-diastole in subjects with normal ventricular function when in the supine position.


Determination and importance of the magnification factor in the calculation of ventricular volume: development of a simple, accurate method. A study of single-plane right anterior oblique left ventricular angiography was undertaken to determine the importance of obtaining correct positioning of a magnification grid and to develop a simple but accurate technique to minimize magnification errors. Theoretical and experimental volume determinations demonstrated 3% to 28% volume errors for grid placement errors ranging from 1 centimeter to 5 centimeters. An experiment was designed whereby cross table lateral radiographs of the chest were taken during contrast injections of the left ventricle. The relative position of the left ventricular center was found at a point 66% of the distance from the anterior to the posterior margin of the heart. Finding this point on noncontrast lateral films of the chest for positioning of a square centimeter grid should yield a more accurate determination of the magnification factor than other current emperic methods.


Anomalous origin of the right coronary artery above the left sinus of Valsalva. Various anomalies of coronary arterial origin have been described. These anatomical variations are discovered either by coronary angiography or at autopsy. We are reporting a case of anomalous origin of the right coronary artery above the left sinus of Valsalva. To our knowledge, this anomaly has not been described before. A technique for selectively catheterizing such an aberrant coronary artery is described.


Anomalous origin of the left coronary artery from the right sinus of Valsalva. We present the clinical, angiographic and surgical findings in a 63-year-old man with anomalous origin of the left main coronary artery from the right sinus of valsalva. The course of the left main artery was abnormal in that it passed between the aorta and the pulmonary artery; in addition, there was obstructive disease involving the left main coronary artery. The association of these two entities in this age group is unusual.


Sudden death in severe aortic stenosis following cardiac catheterization. Five patients with critical aortic stenosis (aortic valve area 0.6 cm2 or less) died 2 days to 21 days following cardiac catheterization performed in anticipation of cardiac surgery. A sixth patient was successfully resuscitated for spontaneous ventricular fibrillation, and successful aortic valve replacement was accomplished. Two patients had prior history of syncope; one patient, of ventricular tachycardia; three patients, of pulmonary edema; and three patients, of crescendo angina. One patient had severe hypotension during maintenance hemodialysis for chronic renal failure. The mode of death was sudden but not witnessed in two patients. The terminal cardiac rhythms were slow junctional in one patient, idioventricular in one, ventricular tachycardia in one, and ventricular fibrillation in the fourth patient. We conclude that symptomatic patients with critical aortic stenosis should be monitored after cardiac catheterization, and surgery should be performed as soon as possible since sudden death is not unusual.


Problems in the detection of acute severe mitral insufficiency using flow-directed catheters. A case of acute severe mitral insufficiency is described wherein bedside Swan-Ganz right heart catheterization failed to established the diagnosis. Emphasis is given to problems inherent in recording the diagnostic large dominant V-waves with this technique, and to the necessity of resolving conflicting measurements with conventional cardiac catheterization.


Uptake of melanosomes and increased melanin formation by cultured melanoma cells after treatment with isolated melanosomes. Melanosomes isolated from a subcutaneous Harding-Passey mouse melanoma and purified by density gradient centrifugation were labelled in vitro with 14C-tyrosine or 3H-dihydroxyphenylalanine in the melanin portion. Incubation of monolayer cultures of Harding-Passey melanoma cells during exponential growth phase (wherin cells contained relatively few melanosomes) with isolated and labelled melanosomes during a time-period of up to 3 days resulted in rapid cellular uptake of label (reaching a saturation level after about half a day). Following a lag period of several hours, the melanin content rose near-linearly in the course of 3 days. Comparison of curves of uptake of radioactivity and melanin concentration indicates that the latter rise is due primarily to newly formed melanin. Ultrastructural studies revealed a strikingly increased number of melanosomes in melanosome-treated cells. Some of these appeared to be the result of phagocytotic uptake. In fact, invagigations of the plasma membrane containing exogenous melanosomes were observed. Since most intracellular melanosomes were localized directly in the cytoplasmic matrix, dissolution of the phagosome membrane appeared to have taken place. Aggregates of melanosomes either surrounded by a membrane or free in the cytoplasm were also observed. These bodies might represent phagolysosomes or/and centres for the formation of new melanosomes. The combined biochemical and ultrastructural findings suggest stimulated melanogenesis induced by phagocytized melanosomes.


Inhibitory effects of the herbicide trifluralin on the establishment of the clover root nodule symbiosis. Trifluralin, a widely used herbicide (Rahman, 1977), may act via interaction with plant microtubule protein (Hess and Bayer, 1974, 1977). In trifluralin treated seedlings of Trifolium repens, root tips increased in diameter and decreased in length, cell elongation was decreased, cell wall deposition was abnormal, root hairs were deformed, and a marked reduction was seen in the number of infection threads induced by the bacterial symbionts. Our observations support the hypothesis that trifluralin (at low concentrations, from 2 x 10(-6) M) interferes with microtubule-based morphogenetic processes in developing seedlings and adversely affects the establishment of the bacteria-legume symbiosis.


In vitro induction of uncoiled chromosomes with inhibitors of RNA and protein synthesis. When inhibitors of cellular DNA, RNA or protein synthesis are added to the growth medium of human lymphoid cells in G2 phase, these agents produce, within narrow ranges of concentrations, G banded or uncoiled chromosomes in the treated metaphase cells. It is suggested that the induced structural alteration is a consequence of an inhibition of the normal chromosome condensation and fusion of bands taking place between prometaphase and metaphase. This inhibition seems to be due to a partial inhibition of G2 phase synthesis of RNA and protein molecules, necessary for normal chromosome condensation in metaphase. It is found that this condensation can be reversed during a resting period after metaphase.


Comparison of determined and undetermined meristems of Selaginella willdenovii Baker. Three types of meristems from Selaginella willdenovii were compared. Undetermined dorsal branch junction meristems were aseptically cultured for 0, 1, 3, 5, and 7 days on Knop's medium prior to fixation. Root tips and shoot tips, which have meristems already determiend developmentally, were excised from intact plants and fixed immediately. The cellular ultrastructure of each meristem was studied showing some differences in chloroplast structure, microtubule deposition, vesicle formation, degree of vacuolation, and invaginations of the plasma membrane. Some of these features, such as microtubule deposition and vesicle formation and vacuolation could be attributed to the different developmental states of the meristems.


Band and nucleolar polymorphisms in polytene chromosomes of Simulium ornatipes (Diptera, Simuliidae). Polymorphisms for the presence or absence of supernumerary bands, for band size, nucleolar expression and the location of secondary nucleolar organisers found in the polytene chromosomes of Simulium ornatipes are described. In all the seven band polymorphisms analysed, six of which involve single bands and one a multiple band complex (IILH), phylogenetic evidence shows that there has been an addition of material. IILH consists of seven amplified C-bands, two supernumerary C-bands and a supernumerary segment involving two C-bands and an interband region. These bands are linked to the peracentric inversion IIL-3, five of the bands being located only within inverted segments. Comparison with mitotic chromosomes suggests that IILH heterochromatin is not under replicated in polytene chromosomes. Recombination between IILH components occurs at a very low level which is insufficient to disrupt the integrity of the polymorphism. It is concluded therefore that the complex evolved in a sequential series, the origin of IIL-3 being the first step. Single band polymorphisms, some of which are also linked to inversions, show similar heterochromatic properties to the IILH bands. A mechanism of selective DNA sequence amplification is proposed to explain increase in band size and the accompanying heterochromatinization. Most supernumerary bands may be amplifications of submicroscopic bands. Nucleolar organisers show heteromorphism for expression and rare secondary nucleoli are found on all chromosomes. It is argued that a multiplicity of sites for ribosomal genes are distributed in the genome and that selective sequence amplification, similar to that proposed above, can increase these sequences to a functional level at any of the sites. This would explain the lability of nucleolar sites in different blackfly species.


Heterochromatin in mitotic chromosomes of Drosophila nasuta. The heterochromatin in mitotic cells of larval neural ganglia of Drosophila nasuta has been analysed by C-banding and by fluorescence studies. All chromosomes, except the 'dot'-like 4th chromosome pair, carry large blocks of heterochromatin which are darkly stained by C-banding, and which fluoresce uniformly brightly with Hoechst 33258, quinacrine mustard, and acridine orange. These heterochromatic segments make up about 40% of the total metaphase chromosome length. The heterochromatic segments also fluoresce brightly with all the dyes at the anaphase stage. In interphase nuclei, all the heterochromatic segments form a common, compact and homogeneous mass which fluoresces brightly with the three fluorochromes used. The size of the bright chromocentre is similar with all the dyes. It is suggested that the heterochromatic segments of different chromosomes are relatively homogeneous in their DNA base sequences, which are likely to be A-T rich in view of their bright fluorescence with Hoechst 33258 as well as quinacrine mustard.


Differential rates of DNA denaturation and renaturation in situ in relation to the C-banding of Allium cepa chromosomes. Telomeric heterochromatin can be demonstrated in Allium cepa chromosomes when root tip squashes are subjected to a C-banding procedure (treatment with saturated barium hydroxide for 10 min, followed by 1 h in phosphate buffer at 60 degrees C). Acridine orange (A0) staining indicated that the chromosomal DNA was denatured by the alkaline treatment and that it renatured within the first 3-7 min in the hot buffer. The DNA of the telomeres reannealed somewhat faster than the rest of the chromosomal DNA, but the AO staining suggested that all chromosomal DNA was double stranded after 7 min in buffer. Digestion of the chromosomes with a single strand specific nuclease, DNase S1, followed by Feulgen staining, demonstrated that the AO staining gives a somewhat misleading picture of the extent of DNA denaturation and renaturation. The S1 nuclease results showed that the chromosomal DNA was completely denatured by the alkaline treatment, but that a fraction of the DNA reannealed during the deionized water wash that preceded the incubation in hot buffer. Neither controls nor chromosomes subjected to the complete C-banding procedure were affected by S1 nuclease digestion, demonstrating that virtually all of the chromosomal DNA was double stranded both before and after the C-banding process. These results, along with the fact that the appearance of the bands was unaffected when the buffer incubation was performed at high (80 degrees C) or low (40 degrees C) temperature, indicated that differential DNA denaturation and renaturation is unlikely to be responsible for C-banding in this species.


Development of a tubular apparatus in chloroplasts of ageing Cyphomandra leaves. Ultrastructural studies of chloroplasts from leaves of the solanaceous genus Cyphomandra during maturation and early senescence showed unusual activities of the inner chloroplast membrane. Before leaf maturity, released small vesicles and saccules. During continued development these structures apparently produced narrow, irregular small tubules which by short branching, slight enlargement and slight coiling became closely associated to form a relatively small tubular apparatus. In the senescing leaf the inner membrane developed long and enlarged extensions into the matrix which branched and coiled in a few cases so as to isolate bits of matrix which were released into the cytoplasm.


Electron microscopic observations of a possible tubulin synthesis-polymerization complex in oocytes of a pond-skater. Maturing oocytes of Gerris najas display, in ultrathin sections, protein fibrils extending from ribosomes, which are often arranged on ring-like cisternae of rough endoplasmic reticulum. In some cases, the fibrils apparently continue into typical microtubules. The possibility is discussed that the huge amount of microtubules of the egg cell is synthesized and polymerized in the form of specific ribosome-tubulin-filament-microtubule complexes.


Chromosomal polymorphism in Lepidospyris demissus (Coleoptera, Curculionidae). The diploid number of chromosomes in Lepidospyris demissus is 22 including a pair of sex-chromosomes (Xy). However, in its polymorphic forms the diploid number is 23 with three sex-chromosomes (X,yy).


Evaluation of sister chromatid exchanges in Bloom's syndrome. The pattern of sister chromatid labelling and incidence of sister chromatid exchanges (SCE), including the effects of caffeine on SCE, were examined with several techniques in normal human cells and in those of a patient with Bloom's syndrome following 1--3 mitotic cycles. The results indicate, in confirmation of those obtained by others with different cells, that SCE in the cells studied is not due to a post-replication repair process, but more likely involves exchanges between the double strands of chromatids.


Insulin delivery rate in response to glucose infusion in normal and diabetic subjects. The insulin delivery rates were estimated in 8 normal and 8 diabetic subjects from the results of peripheral insulin response to a single bolus iv injection of glucose, taking account of fractionally removed insulin. The delivered insulin response to 0.5 g/Kg body weight of glucose injection was biphasic in normal and diabetic subjects. In normal subjects, 1.7 +/- 0.3 U of insulin was delivered during the first phase (0-10 min) and 5.6 +/- 1.6 U during the second phase (11-60 min). In diabetic subjects, 0.4 +/- 0.2 U of insulin was delivered during the first phase and 1.8 +/- 0.5 U during the second phase. The amounts of delivered insulin during the first and second phases were significantly decreased in diabetics (p less than 0.01). The insulin delivery rates during the first and second phases fitted by the same line to the glucose concentration at each period. This suggests that a common glucoreceptor or glucose-mediated signal of the insulin response might exist during both phases. The glucose-insulin response curves in mild diabetics seemed to be similar to those in the normals, but shifted toward higher glucose levels. This finding suggests that the decreased glucose sensitivity of pancreatic beta cells in mild diabetics can be corrected by high glucose concentrations.


Failure of somatostatin to decrease blood glucose by suppression of extrapancreatic glucagon in severely diabetic depancreatized dogs. Effects of somatostatin on extrapancreatic glucagon secretion in totally depancreatized dogs were examined. Somatostatin infusion at a rate of 3 microgram/min showed a rapid decrease of total glucagon-like immunoreactive materials (total GLI) measured by nonspecific antiserum, AGS 10, and gut glucagon immunoreactivity (gut GI) measured by specific antiserum, AGS 18, in systemic blood. Gut GLI calculated as the difference between total GLI and GI did not decrease significantly within 30 min. No changes of blood glucose were noted. Significant decreases of all glucagon fractions were observed when the rate of somatostatin infusion was increased to 10 microgram/min and prolonged for 90 min, whereas again blood glucose did not change at all. It is concluded that somatostatin inhibits both gut GI and GLI secretion, although gut GLI remains in circulation longer than gut GI. Suppression of gut GI is not effective for the reduction of blood glucose once an extreme hyperglycemia is brought about by insulin deficiency.


Effect of calcitonin on calcium concentration in serum and liver of rats ligated bile duct. The effect of calcitonin (CT) on the serum and liver calcium is examined in rats ligated the bile duct. The subcutaneous administration of CT (80 MCR mU/100 g BW) significantly prevented the increase of serum calcium concentration after a single oral injection of calcium (50 mg/100 g BW) to sham-operated rats. But the ligation of bile duct prevented the hypocalcemic effect of CT. Meanwhile, CT significantly increased the liver calcium content after the calcium injection to sham-operated rats. However, the liver calcium content after CT administration was markedly elevated by the ligation of bile duct in comparison with that of sham-operated rats. The present results suggest that the liver calcium increased by CT administration secretes into the bile.


Nuclei and DNA-binding form of the steroid receptor complex in the liver and the ventral prostate of rats. Repeated treatments of the liver cytosol prelabeled with 3H-dexamethasone with DNA-cellulose followed by treatments with purified liver nuclei enabled us to assess the amount of two forms of dexamethasone-receptor complex, one binds only to nuclei and the other binds to DNA and nuclei. The comparable amount of these two forms of the receptor complex was detected in the dexamethasone-labeled liver cytosol, while only one form which binds only to nuclei was found in the liver cytosol labeled with antiglucocorticoid, cortexolone. The significant amount of receptor complex which binds to DNA and nuclei was not present in the cytosol from the ventral prostate preincubated with 3H-dihydrotestosterone.


Effect of HCG on human corpus luteum of menstruation and early gestation. In order to evaluate the luteotropic effect of human chorionic gonadotropin (HCG) on the human corpus luteum, HCG was administered at the menstrual luteal phase and early gestation. Serum progesterone (P) and estradiol (E2) levels were compared after determination by radioimmunoassay. At the mid-luteal phase, although E2 secretion did not increase significantly, P secretion showed a significant increase and peaked 6-8 hr after intravenous injection of 20,000 IU HCG. Three intramuscular injections of 5,000 IU HCG were administered every other day. An increase in sex steroid production and prolongation of luteal span occurred when HCG was administered in the +7 to +11 day period (following LH peak), rather than the +3 to +7 day period. During early pregnancy (from 5 to 10 weeks' gestation) in threatened abortion cases followed by either normal continuation of pregnancy or abortion, neither a single high dosage of HCG (20,000 to 100,000 IU) nor 20,000 IU per day for 7 days produced any significant change in sex steroid secretion. From these observations, it is likely that exogenous HCG shows a luteotropic effect on the human corpus luteum during menstruation, but not during gestation.


Quantitative and qualitative estimation of urinary kallikrein in a patient with Bartter's syndrome. Urinary kallikrein in a patient with Bartter's syndrome was remarkably higher than normal. Indomethacin treatments increased serum potassium concentration and urinary Na/K ratio, and improved the response of blood pressure to angiotensin II infusion, while it decreased plasma renin activity, plasma aldosterone and urinary kallikrein. The purified urinary kallikrein had one component of the iso-electric point 4.3 by isoelectric focusing using Ampholine system, and its molecular weight was 4.2 x 10(4), which was greater than those of three components of normal human urinary kallikreins (normal HUK). Also Km values with TAME and BAME of urinary kallikrein in our patient with Bartter's syndrome did not correspond to those of normal HUK. Thus it can be said that urinary kallikrein in our patient with Bartter's syndrome was qualitatively different from normal HUK. The present observation might be a reflection of renal tubular dysfunction in this patient with Bartter's syndrome.


Effect of vasopressin on intracranial pressure of rabbit. Effect of vasopressin on intracranial pressure (ICP) was examined by an intraventricular administration of the hormone to a rabbit. ICP was determined at the cisterna magna with a manometer and recorded automatically with a recorder. An injection of over 150 micro U of vasopressin lowered ICP, but there was no clear dose-response relationship of the effect of vasopressin on ICP. When vasopressin was injected intraventricularly after lowering ICP by an intravenous injection of acetazolamide which inhibits the production of cerebrospinal fluid (CSF), an additive effect of the hormone on ICP was observed. The effect of vasopressin on excretion of water in CSF was examined by the determination of drainage of tritiated water injected into the lateral ventricle of a rabbit. Drainage of radioactive water into vein was measured by collection of blood at the internal jugular vein and radioactivity of the plasma was counted. Vasopressin accelerated excretion of tritiated water into vein. These results indicate that vasopressin facilitated drainage of CSF into vein to lower ICP.


Dexamethasone suppressibility of plasma pregnenolone (3 beta-hydroxy-5-pregnen-20-one) in normal men. In order to examine the dexamethasone suppressibility of plasma pregnenolone, 9 a.m. and overnight suppression tests were performed in normal adult subjects and plasma pregnenolone levels were radioimmunoassayed. The results were as follows: 1) In the 9 a.m. test, plasma pregnenolone was suppressed to the lowest level at the time between 30 min and 2 hr after dexamethasone; 2) there was no significant difference in dexamethasone suppressibility of plasma pregnenolone between the 9 a.m. test and overnight test; 3) there was no significant difference from each other among the plasma pregnenolone levels after dexamethasone administration (0.5 mg to 3 mg) in both tests; 4) after dexamethasone administration, plasma pregnenolone was not suppressed below 40% of the basal level in both tests; 5) discussions were made about the results, comparing with those of the suppressibility of cortisol which were previously reported from this laboratory.


Radioimmunoassay of human calcitonin using labeled [Asu1, 7]-human calcitonin analogue. Application of synthetic human calcitonin analogue ([Asul,7]-hCT) was attempted, since it is chemically more stable than native hCT. [Asu1, 7]-hCT was successfully labeled with 125I to a specific activity ranging from 410 to 540 microCi/microgram. Sensitivity, recovery and reproducibility of the assay system using 125I-labeled [Asu1,7]-hCT analogue, standard synthetic hCT and its antibodies, were 49 pg/ml, 99.8 +/- 4%, and 7.95% (C. V. within assay) or 21.9% (C. V. between assays), respectively. The dilution curve of the sera obtained from patients with medullary carcinoma paralled well with the standard curve. 125-I-labeled [Asu1, 7]-hCT analogue can be used for routine radioimmunoassay of hCT.


Report on a case of functioning thyroid carcinoma provoking thyrotoxicosis with review of literature. A 57-year old woman with thyroid carcinoma manifesting overt thyrotoxicosis is presented. After the patient had been made euthyroid with propylthiouracil, right lobectomy and lymph node dissection were performed. Permanent paraffin sections revealed follicular adenocarcinoma with capsular and vascular invasion. Metastases to the right humerus, both femurs, the skull and pleural cavity became prominent with the recurrence of thyrotoxicosis and the patient died 2 years and 3 months after operation. The clinical evidence indicates that thyrotoxicosis in the present case is caused by the excessive secretion of thyroid hormone by both the original carcinoma and the secondary deposits. Twenty three similar cases reported in the English and Japanese literatures are summarized.


Insulin secretion after oral calcium load. Oral glucose tolerance test with 50 g glucose was carried out with and without simultaneous oral administration of 3 g calcium lactate. Blood sugar and serum immunoreactive insulin (IRI) were measured before and 30, 60, 90 and 120 min after glucose load in 11 diabetics and 11 non-diabetics. Similar oral glucose tolerance test was performed with and without intravenous administration of 10 ml 8.5% calcium gluconate in 6 diabetics and 6 non-diabetics. Maximum serum level after glucose load (Max IRI), maximum rise of serum IRI following glucose load (Max delta IRI), maximum delta IRI/delta BS following oralglu cose load (Max delta IRI/delta BS), the area surrounded by the delta IRI curve and the abscissa (sigma delta IRI) and the area surrounded by the delta IRI/delta BS curve and the abscissa (sigma delta IRI/delta BS) significantly increased in diabetics but not in non-diabetics after oral calcium load, whereas intravenous calcium load failed to influence any of these values. Oral calcium load thus appears to augment glucose-induced insulin secretion only in diabetics, suggesting some abnormality in the mechanism of insulin secretion with reference to calcium in diabetes mellitus.


Aspects of consumer satisfaction with brief family therapy. In an evaluative study of brief family therapy, 279 families were administered a Family Satisfaction Questionnaire in their own homes, six months after treatment terminated. This questionnaire was designed to assess several aspects of the families' satisfaction with services received. The identified patient in all families was a child with academic and/or behavioral problems at school. A variety of outcome measures were also obtained both at treatment termination and at the six-month follow-up. Families were generally satisfied with the overall services received but expressed widely varying degrees of satisfaction with various aspects of treatment. Very little dissatisfaction was expressed regarding the availability of services (less than 7 per cent), but a sizeable proportion of families (45 per cent) did not feel that the services provided were comprehensive and adequate. Despite concerns regarding comprehensiveness and adequacy of the service, the majority of families were functioning well at the time of follow-up as assessed by a number of independent measures. Global satisfaction should not be regarded as the only index of treatment effectiveness, as many families who were dissatisfied experienced successful treatment outcomes.