The regulation of cell proliferation by calcium and cyclic AMP.

Calcium, in partnership with cyclic AMP, controls the proliferation of non-tumorigenic cells in vitro and in vivo. While it does not seem to be involved in the proliferative activation of cells such as hepatocytes (in vivo) or small lymphocytes (in vitro), it does control two later stages of prereplicative (G1) development. It must be one of the very many regulatory and permissive factors affecting early prereplicative development, because severe calcium deprivation reversibly arrests some types of cell early in the G1 phase of their growth-division cycle in vitro. However, calcium more specifically and much more often regulates a later (mid or late G1) stage of prereplicative development. Thus, regardless of its severity or the type of cell, calcium deprivation in vitro or in vivo reversibly stops proliferative development at that part of the G1 phase in which the cellular cyclic AMP content transiently rises and the synthesis of the four deoxyribonucleotides begins. The evidence points to calcium and the cyclic AMP surge being co-generators of the signal committing the cell to DNA synthesis. The evidence is best explained so far by the cyclic AMP surge causing a surge of calcium ions which combine with molecules of the multi-purpose, calcium-dependent, regulator protein calmodulin (CDR) somewhere between the cell surface and the cytosol. The resulting Ca-calmodulin complexes then stimulate many different (and possibly membrane-associated) enzymes such as protein kinases, one of which produces the DNA-synthetic initiator. Calcium has little or no influence on the proliferation of tumor cells. Some possible explanations of this very important loss of control are considered.


The wavelength dependence of 8-methoxypsoralen photosensitization of radiation-enchanced reactivation in a mammalian cell-virus system.

The combined effect of 8-methoxypsoralen (8-MOP) and ultraviolet (UV) radiation on the ability of an irradiated mammalian cell (CV-1) to reactivate UV-irradiated mammalian virus (Herpes simplex) was tested. Prior treatment of cells with 8-MOP was found to increase Radiation-Enhanced Reactivation (RER) at one wavelength (297 nm) in the far ultraviolet but not at others (240-289 nm). This same treatment induced RER in the near UV (302-370 nm) and the visible region (380-400 nm). An action spectrum for the photo-sensitized induction of this cellular parameter was obtained. This action spectrum is consistent with the absorption spectrum for 8-MOP and the theory that damage to DNA is, at least in part, responsible for Radiation-Enhanced Reactivation.


An effect of cell-culture passage on ultraviolet-enhanced viral reactivation by mammalian cells.

The ability of ultraviolet-irradiated African green monkey kidney cells to reactivate UV-damaged herpes simplex virus was tested over a range of 57 passages (24-81). Several types of controls were employed to minimize daily variations. The results indicate that in this system cells demonstrate an increasing efficiency to reactivate UV-damaged virus until approx. passage 60, followed by a decrease in this ability beyond this passage. Chromosome counts at selected passages revealed no significant change in chromosome number as a function of passage. The mechanism(s) or factor(s) causing this effect are unknown.


Splicing of the late mRNAs of polyoma virus does not occur in the cytoplasm of the infected cell.

The three mRNAs that encode the capsid proteins of polyoma virus are produced by the excision of different sequences from continuous transcripts of the L strand of viral DNA. All three of the mRNAs have long half lives, and the larger species are not converted to the smaller ones to any measurable extent within the cytoplasm. Therefore the cytoplasmic proportions of late polyoma mRNAs are predetermined by splicing that is confined to the nucleus of the infected cell and which is complete by the time that mRNA is transported to the cytoplasm.


Simultaneous ultrastructural demonstration of multiple peptides in endocrine cells by a novel immunocytochemical method.

Current immunocytochemical techniques detect all antibodies that react with tissue. Unfortunately, some of these antibodies may react with antigens other than those intended. Such problems are minimised by using sets of antibodies detecting different regions of the desired antigen. However, as immunocytochemical methods can now detect very low antibody concentrations, the purity of antisera is critical. Furthermore, although antisers may be purified by affinity chromatography, difficulties in recovering high-avidity antibodies cause most affinity-purified antisera to be enriched in low-avidity antibodies, which may be dislodged during staining. We have therefore developed, and describe here, a new ultrastructural post-embedding staining technique, based on the divalency of IgG molecules and using antigen-coated colloidal gold granules. Previously, colloidal gold-labelled antibodies have been used for post-embedding staining. Unlike our gold-labelled antigen detection (GLAD) technique, however, these methods do not differentiate between specific and nonspecific antibodies. The GLAD method detects only specific antibodies and does not select against high-avidity antibodies, and in this it resembles the radioimmunocytochemical method. However, the GLAD method differs from the latter in that it is useful for ultrastructural studies, does not require autoradiography and allows simultaneous detection of multiple antigens. Moreover, specific activity compared with background may be quantitated.


Regulation of glutamate receptors by cations.

Current evidence suggests that glutamate is a major excitatory neurotransmitter in the mammalian central nervous system (CNS); particularly, glutamate excites most neurones in the CNS. Until recently this effect was widely used to study glutamate receptors and to distinguish them from those of other excitatory amino acids. The development of ligand binding studies for many neurotransmitters has facilitated the study of receptors at the molecular level and using these methods we recently reported the existence in hippocampal membranes of pharmacologically distinct sodium-dependent and sodium-independent glutamate binding sites, the former related to high-affinity uptake and the latter exhibiting several characteristics of postsynaptic receptor sites. We now report that, as with other neurotransmitters, several ions regulate the Na-independent binding of glutamate; the monovalent cations induce a decreased binding while certain divalent cations enhance this Na-independent binding. Additionally, since some of these effects appear to be irreversible, we propose that the regulation of glutamate binding by cations might account for the extremely long-lasting potentiation of synaptic responses found in the hippocampus following bursts of repetitive electrical stimulation (see ref. 9 for a review).


Mutant avian erythroblastosis virus with restricted target cell specificity.

Avian erythroblastosis virus (AEV) induces a fatal erythroblastosis within 2 weeks of intravenous injection in chicks in virtually 100% of cases. In chicks injected intramuscularly, sarcomas frequently develop at the site of injection before the animals die from erythroblastosis. In vitro, AEV transforms both erythroblasts, derived from bone marrow cultures, and fibroblasts. These effects have been shown to be a general property of AEV and not of separate leukaemia- and sarcoma-inducing forms of the virus. AEV is defective for replication and can be propagated only in the prewence of helper virus. Its transformation specificity is independent of the helper virus used. It is not clear whether AEV has two different genes controlling transformation of the two types of target cell or whether it has only one gene coding for both. To investigate this question, we looked for mutants of AEV unable to transform one of the two types of target cell. We now describe such a mutant, which is defective for erythroblast transformation but which can still transform fibroblasts.


Isolation of a replication-defective murine leukaemia virus from cultured AKR leukaemia cells.

Mice of the AKR strain are characterised by a high incidence of spontaneous thymic lymphomas. AKR chromosomes contain the genomes of ecotropic murine leukaemia virus (MuLV) at two loci, termed Akv-1 and Akv-2 (refs 2-6). Shortly after birth, the normal tissues of AKR mice begin to produce high levels of this XC-positive MuLV (ref. 7) (that is, one that forms XC plaques). A second class of MuLV, termed mink cell focus-inducing virus (MCF), is produced specifically by preleukaemic and leukaemic AKR thymocytes. Nowinski et al. have established a series of tissue culture lines from AKR leukaemias and reported that the resulting cell lines produce virus particles, but that these particles, surprisingly, do not give rise to XC plaques. We have analysed the virus particles produced by one of these cell lines, termed AKRSL2. We show here that, unlike most or all of the nonmalignant tissues in the AKR mouse, these cultured lymphoma cells produce very little non-defective ecotropic MuLV; however, they do produce replication-defective ecotropic MuLV.


Structure and sequence of the multihaem cytochrome c3.

The molecular structure of cytochrome c3 isolated from Desulfovibrio desulfuricans has been solved on the basis of its crystallographic determination at 2.5 A resolution and of an essentially complete sequence. The molecule consists of a single polypeptide chain wrapped around a very compact core of four non-parallel haems which present a relatively high degree of exposure to the solvent. Alignment of the amino acid sequences of cytochrome c3 from several species suggests that the structure reported here is characteristic of the cytochrome c3 group.


[Quantum analysis of postsynaptic potentials].

Basic formulations of the quantum theory for synaptic transmission are listed. Methods for determining the mean quantum content, quantum value and binomial parameters describing the amplitude distributions of the unitary and "minimal" postsynaptic potentials are discussed. Literature and author's determinations of the quantum parameters for the synapses of the central nervous system are described. The comparison is made with similar determinations for more studied peripheral junctions. Some difficulties and perspective of the quantum theory are discussed.


[Electrophysiologic study of conduction of afferent impulses through the medial geniculate body].

In experiments carried out on cats immobilzed with d-tubocurarine 280 neurons located in pars principalis of the medial geniculate body and 408 auditory cortical neurons located in AI were studied extra- and intracellularly in response to stimulation of the brachium of the inferior colliculus and geniculocortical fibres. It was shown that the initial stage of the reaction observed in the medial geniculate body neurons response to stimulation of the brachium of the inferior colliculus continue for 13.0 ms. Excitation of 72% of neurons participating in the reaction occurs during the first 3 ms after stimulation. 84% of IPSPs arouse in the same period of time. It is found that some medial geniculate neurons have axons entering the inferior colliculus. Substantial part of fibres in the brachium of the inferior colliculus comes to the auditory cortex without synaptic switching in the medial geniculate body. 76% of medial geniculate neurons from the group excited monosynaptically are thalamocortical relay neurons and the rest are interneurons. 90% of relay neurons in the medial geniculate body are excited monosynaptically. Many medial geniculate neurons respond to stimulation of the brachium of the interior colliculus by EPSP-IPSP sequence or by primary IPSPs. About 20% of primary IPSPs develop monosynaptically. The maximal amount of IPSPs comes into being disynaptically with the participation of inhibitory interneuron located at the input to the medial geniculate body. The inhibition observed in this case is direct afferent one.


How the size of motoneurones determines their susceptibility to discharge.

The susceptibility of motoneurones to discharge by physiological inputs varies inversely with their size. This relationship has far-reaching consequences for the control of muscular tension, and also accounts for significant differences in the properties of muscle fibres and motor units. The probable basis for the relationship is that the amplitude of excitatory postsynaptic potentials (e.p.s.ps) is also correlated inversely with cell size, but no satisfactory explanation for this finding is known. We now describe experiments which indicate that afferent impulses invade the relatively simple ramifications of fibres going to small motoneurones more completely than the extensive arborisations going to large cells. This results in activation of a higher percentage of the synaptic endings on small cells, which produces larger e.p.s.ps in them and accounts for their greater susceptibility to discharge.


[Heterosynaptic interactions in fields CA1 and CA3 of the hippocampus in vitro].

Heterosynaptic interactions between the perforant path and Schaffer's collaterals in the field CA1 and between the perforant path and dentate mossy fibres in the field CA3 were investigated in guinea pig hippocampal slices. Using the method of paired stimuli, space-time summation (for 20--50 ms) was observed in both systems with stimuli sub-threshold for spike generation. Spike responses of the neurons to testing stimulation of afferents synapsing upon the terminal parts of apical dendrites (perforant path) were depressed after spike discharge to conditioning stimulation of proximal afferents (for about 20 ms in CA1, and for about 300 ms in CA3). With inverse combination of the stimuli the period of suppression was much shorter (3--8 ms). Tetanization of the mossy fibres was followed by prolonged (2--30 min) depression of the CA3 responses to the perforant path stimulation. No other reliable long-lasting posttetanic heterosynaptic effects were observed.


[Responses of the vibrissal projection zone of the cat somatosensory projection zone to afferent activation].

Responses of 375 neurons of SI cortex region in the vibrissae projection zone were recorded in unanesthetized cats: responses to electrical stimulation of infraorbital nerve and mechanical stimulation of vibrissae were studied. Nerve and vibrissae stimulation evoked complex synaptic potentials (short EPSPs followed by IPSPs) in most neurons primary IPSPs were found in other units. The corresponding changes of impulse activity could be recorded in many neurons extracellularly. Initial inhibition was evoked by vibrissae stimulation more frequently (in 45% units comparing to 16% when the nerve was stimulated). Difference of minimal EPSP and IPSP latencies during intraorbital nerve stimulation was 0.8 ms, difference of mean values--1.4 ms. Directional sensitivity of cortical neurons (to the changes in direction of vibrissae deflection) is demonstrated. Neurons located in the close proximity may possess different pattern of directional sensitivity. It is supposed that short latency neuronal inhibition in SI cortical zone is mainly afferent (not recurrent). Probable mechanisms of directional sensitivity of the studied neurons are discussed.


Familial gliomas.

The authors report two pairs of siblings who had intracranial malignant gliomas. Genetic influences in the occurence of gliomas are discussed.


Effect of hippocampus extirpation in the rat on glutamate levels in target structures of hippocampal efferents.

Twenty days after complete uni- or bilateral hippocampus extirpation in rats, a 25% decrease in glutamate concentration was observed in the septum. Glutamate content also decreased in other terminal structures of the hippocampo-subicular system, i.e. entorhinal cortex, nucleus accumbens septi, mammillary bodies and contralateral hippocampus. It is concluded that the fall in glutamate content which is absent in caudate nucleus is specific for target regions of the hippocampal efferents, adding further support to the suggested transmitter role of glutamate in the limbic system.


Differentiation between anti- and orthodromic responses to nerve stimulation in neurons with axo-axonal synapses (Helix pomatia).

In identified neurons of Helix pomatia nerve stimulation evoked depolarizations of short latencies. The mechanisms underlying these potentials were studied by conventional electrophysiological and intracellular staining techniques. Most of the depolarizations behaved like chemically mediated postsynaptic potentials. The remaining responses can be regarded either as antidromic axonal action potentials (APs) or as electrotonic junction potentials. The differentiation between the latter alternatives and hence the identification of the axonal pathways of the impaled neurons proved to be difficult using conventional methods.


The opiate antagonist, naloxone, does not affect descending inhibition from midbrain of nociceptive spinal neuronal discharges in the cat.

Discharges were recorded from spinal dorsal horn neurons in response to noxious skin heating (e.g. 50 degrees C). Repetitive electrical stimulation of the mesencephalic periaqueductal gray (PAG) inhibited these nociceptive discharges. In each of 9 experiments systemic administration of naloxone (1-3 mg/kg) did not affect this descending inhibition, arguing against involvement of endogenous opiates.


Regional distribution of a high-affinity enkephalin-degrading peptidase ('enkephalinase') and effects of lesions suggest localization in the vicinity of opiate receptors in brain.

The distribution of a high affinity enkephalin-dipeptidylcarboxypeptidase between regions of mouse brain is markedly heterogenous and parallels that of opiate receptors. Furthermore intrastriatal administration of kainic acid as well as interruption of the nigrostriatal dopaminergic pathway by 6-hydroxydopamine (6-OHDA) lead to similar decreases in this peptidase activity and in the number of opiate receptors. On the contrary, no correlation was found between low affinity enkephalin degrading enzymes and opiate receptors.


L-glutamate specific [3H]kainic acid binding in the rat neostriatum after degeneration of the cortico-striatal pathway.

Four weeks after lesion of the cortico-striatal pathway, the specific kainic acid binding was reduced by 20% in the neostriatum. It is concluded that the binding sites are most likely not located on cortico-striatal neurons. The displacement of kainic acid by some chemical indicates that the kainic acid binding site is different from the glutamate binding site, as defined iontophoretically.


An epidemic of gastroenteritis in Auckland 1978.

During an epidemic of gastroenteritis which spread throughout New Zealand in 1978, 372 cases of nonbacterial illness were documented in children in Auckland during the months of June and July. A brief account is given of the clinical picture observed. Evidence from virological techniques suggests that some if not all cases were due to rotavirus. The severity of illness may have been greater than most observers to date have noted. From our observations we raise the possibility of air-borne spread, perhaps in addition to faecal-oral. We wish to emphasise that drugs play no part in the treatment of viral gastroenteritis, that home-made electrolyte solutions can be hazardous and that early intravenous therapy can be life-saving.


Two strains of human rotavirus in Auckland.

Polyacrylamide gel electrophoresis of human rotavirus RNA has identified at least two distinct strains of virus currently circulating in Auckland. The sensitivity of the method both for detecting rotavirus infection and for identifying variation in rotavirus strains is discussed.


Methotrexate with citrovorum factor rescue for nonmetastatic gestational trophoblastic neoplasms.

Fifty-one patients with nonmetastatic gestational trophoblastic neoplasms (NMGTN) were treated with either 4 or 6 mg/kg methotrexate (MTX) and citrovorum factor (CF) rescue to determine if the higher dosage could reduce the number of courses of chemotherapy required to achieve remission. Thirty-six of 41 patients treated with 4 mg/kg MTX achieved complete remission with 1 course of chemotherapy. Increasing the initial dose of MTX to 6 mg/kg in 10 patients did not reduce the need for subsequent courses of chemotherapy but did increase associated toxicity. The rate of fall in the human chorionic gonadotropin (hCG) titer following the initial course of MTX-CF was found to be an accurate predictor of therapeutic response. The need for further chemotherapy may be anticipated if the hCG titer has not fallen by 1 log within 18 days.


Endocrine and androgen-receptor studies in a patient with XY gonadal agenesis.

A 19-year-old phenotypic female with gonadal agenesis and XY karyotype underwent an endocrinologic study. She lacked secondary sexual characteristics and there was posterior labial fusion, absence of vagina, and no gonadal or gonadal duct tissues present at laparotomy. Elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) responded well to intravenous injection of LH-releasing hormone (LH-RH) but did not respond to clomiphene citrate. Both OH and FSH levels were suppressed by administration of testosterone or estrogen. Low serum concentration of testosterone did not respond to human chorionic gonadotropin (hCG) injection. Dihydrotestosterone binding by cultured skin fibroblast revealed the existence of a binding component with low capacity and high affinity. This is the first report of a patient with XY gonadal agenesis in whom androgen receptors in the target cells are demonstrated.


Activities of organ characteristic enzymes and noradrenaline and glycogen contents in the Albert hepatoma of C57BL mice.

Further biochemical characterization of the Albert hepatoma has been performed. The following results were obtained: In spite of often repeated transplantations and a medium growth rate, the Albert hepatoma does still contain organ-characteristic enzymes. We have found significant activities of glucokinase, glucose-6-phosphatase and arginase, and considerable amounts of noradrenaline and glycogen. In addition, it is capable to respond to humoral stimuli, that is, it differs from most of the other hepatocellular malignomas also in this regard.


Primary empty sella turcica in children. Report of two familial cases.

The authors describe cranio-facial deformities found in two sisters and associated with spinal anomalies, short stature and delayed skeletal maturation. The principal radiological features were an enlarged J-shaped sella turcica and intrasellar cisternal herniation. Enlargement of optic foramina and internal acoustic canals were also present. These asymptomatic cases of "empty sella" seem to be part of a general dysplastic syndrome rather than a local disease.


A case of hypertrophic protein losing gastropathy.

A 3 1/2 year old boy presented with a history of vomiting and generalized oedema. Biochemically proven protein losing enteropathy was associated with huge gastric fundal rugae on barium examination. Gastroscopy confirmed the barium findings but biopsy material demonstrated normal mucosa. The condition regressed on a high protein diet. Cytomegalovirus (CMV) was found in the urine after the illness had subsided.


Mixed and obstructive sleep apnea and near miss for sudden infant death syndrome: 2. Comparison of near miss and normal control infants by age.

Twenty-nine full-term near miss for sudden infant death syndrome (SIDS) and 30 normal control infants underwent 24-hour polygraphic monitoring. Several types of respiratory events during sleep (eg, central, mixed, and obstructive apnea, periodic breathing) were defined and tabulated. Analysis of these respiratory variables and comparison of groups of near miss and control infants indicated that between 3 weeks and 4 1/2 months of age only one variable was consistently different at a statistically significant level: the number of mixed and obstructive apnea greater than 3 seconds during total sleep time. This study also showed an increase in mixed and obstructive respiratory events during sleep at 6 weeks of age in control as well as in near miss infants.


"It's time, you must wake up now".

Seven subjects who claimed to be able to awake accurately from sleep at a predetermined time were required to awake in the sleep laboratory at 03:30 and 05:30 on two separate nights. Eight of the 12 spontaneous awakenings were within +/- 20 min. from the target time, and 8 awakenings were from REM sleep. The two best performing subjects were tested for additional 7 nights in the laboratory but accuracy deteriorated considerably with only 2 awakenings within +/- 20 min. from target time. Approximately 50% of all awakenings, however, were from REM sleep. It is concluded that some individuals are able to awake at predetermined times and that this ability might be dependent on motivational level and the sleep stage.


Distortions of vision and pain: two functional facets of D-lysergic acid diethylamide.

D-lysergic acid diethylamide (LSD) produces distortions of visual perception and analgesia. Evidence is advanced from a functional standpoint that the observed visual effects result from an attenuation of light-evoked input to the dorsal lateral geniculate nucleus (LGN) from the purely centripetal pathways of the retina. More slowly responding visual afferents or those with more complex receptive fields seem to be affected most. LSD analgesia, accompanied by severe psychotic symptoms, appears to result from drug actions on a centrifugally controlled pain system involving neurons of the midbrain raphe.


Determination of the length distribution of poly(A) at the 3' terminus of the virion RNAs of EMC virus, poliovirus, rhinovirus, RAV-61 and CPMV and of mouse globin mRNA.

Rapid, detailed, and accurate analysis of the length spectrum of 3' terminal poly(A) in an RNA population can be obtained by 3'-terminal 32P-labelling of RNA with T4 RNA ligase, digestion with ribonucleases T1 and A, and use of gel sequencing methods. Length distributions of 3'-terminal poly(A) of EMC virus, poliovirus, rhinovirus, RAV-61, and CPMV virion RNAs as well as mouse globin mRNA are presented.


A convenient sequencing method for 5' protein-linked RNAs.

A convenient nucleotide sequencing method for 5' end protein-linked RNAs was developed. Genome of LSc, 2ab poliovirus, which has a protein (VPg) covalently linked to the 5' terminus, was labelled with 125I Bolton and Hunter reagent after proteinase K treatment. No sign of labelling of nucleotide moiety in the genome with the reagent was detected. A labelled oligo peptide-linked ribonuclease T1 fragment was obtained from the 5' end of the genome. Analysis of the complex by two dimensional gel electrophoresis after partial alkali digestion or by the nucleotide sequencing method of Donis-Keller et al. (1) revealed that LSc, 2ab strain genome had an identical 5' end structure to that of Mahoney strain genome, that is, VPg-pUpUpApApApApCpApGp. Our results have shown that this labelling method is useful for analysis of 5' end sequence of RNAs linked to protein at the 5' termini.


Malignant fibrous histiocytoma of bone and osteosarcoma. A comparative light and electron microscopic study.

Malignant fibrous histiocytomas are well-described tumors of the soft tissues. Recent investigations have shown that malignant histiocytoma may also occur as a primary bone tumor. However, difficulties may arise to distinguish malignant histiocytoma of bone from other malignant bone tumors, such as osteosarcoma. In the present study, the ultrastructure of five cases of malignant fibrous histiocytoma of bone is compared with that of osteosarcoma. The results show that malignant fibrous histiocytoma is composed mainly of histiocytic cells and fibroblastic cells. In addition, xanthomatous cells, undifferentiated cells, and giant cells may be observed. By contrast, the predominant cell type in osteosarcoma is the neoplastic osteoblast, characterized by abundant rough endoplasmic reticulum. Signs of matrix calcification in the intercellular matrix between the collagen fibrils are regularly observed in osteosarcoma, but not in malignant histiocytoma. From these results it is concluded that the ultrastructure of malignant fibrous histiocytoma arising in bone is morphologically identical with the soft tissue counterpart of this tumor. The components of the tumor are derived from neoplastic histiocytes. This cytogenesis differs from that of osteosarcoma, which is derived from neoplastic osteoblasts. Therefore, from the ultrastructural point of view, malignant fibrous histiocytoma of bone should be accepted as a distinct histologic entity among bone tumors.


Ectopic ACTH syndrome from bronchogenic carcinoma in association with chronic lymphocytic leukaemia.

A patient under treatment for chronic lymphocytic leukaemia developed lobar pneumonia after 8 months. When antileukaemic therapy was discontinued, features of an ectopic ACTH syndrome developed, secondary to bronchogenic carcinoma. Exogenous steroid therapy for leukaemia seemed to suppress the clinical manifestations of the ectopic ACTH syndrome while subsequent endogenous steroid production controlled the peripheral lymphocyte count.


Genetic nature of regression of Rous sarcoma virus-induced tumors in crosses of Regional Poultry Research Laboratory lines 6 and 7(2).

Regional Poultry Research Laboratory (RPRL) inbred lines 6(1), 6(3), and 7(2) and F1, F2, and reciprocal backcross progenies of these lines were used to investigate host-gene effects upon the regression of Rous sarcoma virus (RSV)-induced tumors. Lines 6(1) and 6(3) were susceptible to subgroup A and C lymphoid leukosis (LL) viruses and line 7(2) was resistant to subgroup A but was segregating for susceptibility to subgroup C LL virus. Viruses of RSV subgroups A and C were used. Lines 6(1), 6(3), and 7(2) were homozygous for shared blood group alleles B2, C5, L1 and r. The incidence of tumor regression was higher in line 6(3) than in 7(2), and in reciprocal F1 crosses of these lines was of the same order of magnitude as in line 6(3). Progeny from F1 generation parents mated to line 6(3) had a higher frequency of regression than offspring from F1 generation parents mated to line 7(2). The frequency of regression in F2 generation offspring was intermediate between the two backcrosses. The data suggest that either a locus (or loci) other than L and B has a role in Rous tumor regression in this species or the immune response region of the B blood group-major histocompatibility complex differs in the two lines even though the serological and/or graft vs. host regions have not been shown to differ.


Development of gluconeogenic, glycolytic, and pentose-shunt enzymes in the chicken kidney.

The activities of the key gluconeogenic, glycolytic, and pentose-shunt enzymes in chicken kidney were determined starting from 8 days before to 58 days after hatching. The activities of pyruvate carboxylase (PC), mitochondrial and cytosolic phosphoenolypruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (FDPase) and glucose-6-phosphatase (G6Pase) were low in the embryonic tissue but increased towards the time of hatching. After hatching, the activities of PC, mitochondrial PEPCK, and G6Pase continued to increase, but those of FDPase and cytosolic PEPCK decreased. Relatively little change in these activities was observed in chickens over 24 days old. The activities of hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) increased during embryonic growth. After hatching, HK activity continued to increase and then decrease, whereas PFK appeared to decrease and then increase to prehatch levels in 28-day-old birds. LDH activity continued to increase until 8 days after hatching and remained constant thereafter. No definite pattern was discernible in the case of PK. As for the pentose-shunt enzymes, there was no significant change in glucose-6-phosphate dehydrogenase activity (G6PDH), but the activity of 6-phosphogluconate dehydrogenase (6PGDH) increased until the chickens were 14 days old and then remained relatively constant.


[Change in the phosphatase activity in rice seeds of varying germination].

Activities of ATPase, acid and alkaline pyrophosphatases and phytase in the germs and endosperms of rice seeds of varying germinative power were measured during their swelling and germination. Maximum ATPase activity was found in the cytoplasmic fraction. Activity of pyrophosphatase was higher in the germ and that of phytase in the endosperm. As the swelling and germination continued, the enzyme activity increased. Losses of germinating power during prolonged storage were accompanied by a decline in the activity of the enzymes which, however, never disappeared; the activity of pyrophosphatases was maintained by 55-70% and that of ATPase and phytase by 40-44%.


[Rapid biological method for assessing D-vitamin supply of chicks].

A segment of the small intestine of chicks turned inside out and pulled on a glass rod was placed into a buffer solution. The Ca2+ consumption from the solution was monitored, using the color murexide reaction. The Ca2+ binding during the first 5 min was much higher in the chicks well supplied with D-vitamin than in the D-vitamin deficient chicks. The level of binding was determined by the content of specific calcium-binding protein in the intestinal mucosa. A close correlation between the dosage of D3-vitamin and the amount of Ca2+ consumed by the intestine from the solution and bound with the mucosa was established. These findings together with the simplicity of the procedure suggest that measurement of the calcium binding capacity of an intestinal segment can be used as a rapid method of assaying the D-vitamin status of the animal.


[Synthesis of D-ribulose-1,5-diphosphate with immobilized enzymes of Thiobacillus].

Preparative synthesis of D-ribulose-1,5-diphosphate (RuDP) from ribose-5-phosphate and ATP was carried out, using as a catalyst a crude extract of Thiobacillus thiooxidans 58 R immobilized on porous glass. The methods for immobiliztion of crude bacterial extracts, synthesis of RuDP and purification of the resultant product by means of column chromatography on activated charcoal and anionites were developed. The structure of RuDP was identified by 13C-NMR spectroscopy. Stability of two phosphate groups of RuDP during acid and alkaline hydrolysis proved to be different: both phosphate groups were completely removed in 1 N H2SO4 at 100 degrees C whereas only one phosphate group was hydrolysed in 1 N NaOH at 25 degrees C. This finding is at variance with the earlier results of Horecker et al. (1956).


Effects of acetazolamide and changes of acid-base balance on the content of cyclic nucleotides in the rat kidney.

Changes in tissue levels of cyclic adenosine 3':5'-monophosphate (cAMP) and cyclic guanosine 3':5'-monophosphate (cGMP) in the rat kidney in response to acid-base changes and administration of acetazolamide were measured. cAMP was determined according to the method described by Gilman and cGMP by radioimmunoassay. 1 mg/kg acetazolamide increased bicarbonate excretion 100-fold over the control values to 2.52 +/- 0.5 mEq/min (mean +/- SEM; n = 6), but did not influence cGMP and cAMP tissue content. 10 and 100 mg/kg acetazolamide increased cGMP tissue levels to 0.277 +/- 0.048 and 0.482 +/- 0.07 pmol/mg dry weight in comparison to 0.192 +/- 0.04 in the controls, whereas no changes in cAMP levels occurred. Chronic as well as acute metabolic alkalosis induced an increase of cGMP levels (0.26 +/- 0.03 and 0.29 +/- 0.06 pmol/mg), whereas chronic metabolic and acute respiratory acidosis lowered cGMP levels to 0.14 +/- 0.02 and 0.13 +/- 0.02 pmol/mg. cAMP tissue levels were not affected by changes in acid-base balance. The data could suggest that cGMP participates in the regulation of acid-base balance and renal effects of acetazolamide.


Reactivity of isolated bovine facial vessels to electric stimulation and to drugs.

The effects of electric stimulation on isometric force generation of isolated helical strips of bovine facial arteries (BFA) and veins (BFV) were investigated. Whereas BFA always contracted, electrically stimulated BFV showed a biphasic response, i.e. a small, transient contraction followed by an intense relaxation. The findings presented suggest a neurogenic response for the vasodilator component of BFV response to electric stimulation. Exogenous catecholamines and serotonin dilated the veins; the effects were antagonized by propranolol and dihydroergotamine, respectively. Dopamine-induced relaxations were only partially inhibited by propranolol; the residual relaxations were antagonized by chlorpormazine and haloperidol. Relaxations of the veins after electric stimulation or after administration of noradrenaline were accompanied by an increase of the cAMP content. In the BFA catecholamines, serotonin and histamine increased the tension, whereas isoprenaline was ineffective. Acetylcholine contracted the veins and relaxed the arteries; both effects were antagonized by atropine.


Analgesia induced by cold-water stress: attenuation following hypophysectomy.

In addition to the well-known activation of the pituitary-adrenal axis, acute exposure to severe stressors includes a temporary analgesia in rats. Thus, the present study investigates whether the pituitary was involved in the mediation of analgesia induced by severe cold-water swim (CWS) stress. Flinch-jump thresholds were measured 30 min following 3.5-min swims in water temperatures ranging from 2-35 degrees C. Compared with untreated normal rats, hypophysectomized rats, receiving corticosterone and thyroxin, displayed significantly less CWS-induced analgesia, while similarly-supplemented normal rats exhibited significantly more CWS-induced analgesia. In a second experiment, operant liminal escape pain thresholds were determined following acute and chronic CWS. Whereas normal rats exhibited profound analgesia following the initial swims, the hypophysectomized rats never displayed any CWS-induced operant escape shifts. Stress-induced alterations in general activity levels and/or thermoregulation were shown to be unrelated to the diminished effectiveness of CNS to produce analgesia in hypophysectomized rats. These data imply that the pituitary is involved in the mediation of CWS-induced analgesia.


Some effects of an ACTH 4-9 analog (Org 2766) on human performance.

The effects (on human beings) of the ACTH analog Org 2766 were investigated for a range of performance tests: complicated serial reaction task, running memory span, verbal learning and non-verbal mental ability tests (closure flexibility and non-verbal abstraction). Subjective ratings on feelings were taken and heart rate was measured. Only the 30-min reaction task produced significant drug effects. In this task performance tends to deteriorate as a function of time on task. During the test period there is a gradual increase in the number of lapses in performance due to moments of inattention. This deterioration is counteracted by the ACTH 4-9 analog, a result also found in previous study using ACTH 4-10 (Org OI63). Thus ACTH fragments which are devoid of endocrine effects seem to have a beneficial effect on goal-directed motivation oriented on the requirements of the task.


Neuromuscular transmission in some hindlimb muscles of piglets with congenital myofibrillar hypoplasia (splayleg).

Seventeen new-born piglets of hybrid stock were tested for defects of neuromuscular transmission by stimulation electromyography (EMG). Nine of these displayed extreme symptoms of muscle weakness (splayleg), while the others were their clinically normal littermates. Muscles from four different functional groups were investigated, including the gastrocnemius, tibialis anterior, knee flexors and thigh adductors. Repetitive stimulation of muscle nerves at 3 Hz gave comparable peak-to-peak amplitudes of the EMG response in splayleg and control piglets (mean values from 5 to 10 mV). The lowest mean EMG response values at this stimulation frequency were found in splayleg adductor muscles of the thigh which were not, however significantly different from the controls. Higher frequencies of stimulation (30, 50 and 100 Hz), in general, led to a less pronounced decrease of EMG amplitude in splayleg piglet muscles than in the controls, with the exception of knee flexors. Neither splayleg nor control muscles exhibited post-activation exhaustion or post-tetanic potentiation. It is being concluded from these results that congenital myofibrillar hypoplasia is not primarily a myasthenia-like syndrome, but that either excitation-contraction coupling or the contractile mechanism itself are primarily affected.


Depressed affect as a cause of associated somatic problems.

Depressed affect as a cause of associated somatic problems is explored by means of data on affect, appetite, energy, and sleep collected from a community sample and from subsamples contacted after each of several time lags. The analysis of the data indicates that depressed affect is a cause of the major somatic problems associated with it. It is suspected that depressed affect involves continuing high density neural firing which, over a period of months, causes a reduction of post-synaptic biogenic amine receptor cell sensitivity in the brainstem, with the diencephalon as the major site. This results in a functional impairment responsible for the somatic problems.


Characterization of 3H-GABA receptor binding to rat brain synaptosomal membranes: effect of non GABAergic compounds.

Characteristics of 3H-GABA binding to rat brain synaptic membranes in vitro have been investigated. The specific binding of 3H-GABA displays saturation kinetics. Only one single population of receptor sites was found (Km = 31.3 nM) with a concentration of 2.09 pmol/mg protein. Only GABA agonists show inhibitory effect on the binding, whereas GABA antagonists, GABA-uptake inhibitors, and inhibitors of GAD and GABA-T are without effect. The order of potencies for GABA agonists are: Muscimol greater than GABA greater than or equal to 4,5-dihydromuscimol greater than 3-aminoproprane sulphonic acid greater than isoguvacine greater than THIP greater than 3-hydroxy-GABA greater than imidazol-4-acetic acid. Agonists and antagonists from other neurone systems as well as neuroleptics and benzodiazepines had no or only a very slight potency in the binding test.


Personality dependent effects of the ACTH 4--10 fragment on test performances and on concomitant autonomic reactions.

The effect of the ACTH-fragment 4--10 (30 mg SC) on a mental performance test and on some concomitant cardiovascular changes was investigated in comparison with a placebo in a double blind cross-over study. The subjects were either mainly extraverted or mainly introverted according to Eysenck's 'Maudsley Personality Inventory'. Under the influence of the heptapeptide extraverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the placebo. In contrast, under the influence of the placebo introverted subjects achieved a higher total score in the mental task performance with a smaller increase of forearm blood flow and of heart rate than under the influence of the ACTH-fragment. Personality, therefore, determines to some degree how this centrally acting heptapeptide influences efficiency in the mental task performance and the concomitant cardiovascular changes.


[Bronchial arteriography and intraarterial chemotherapy in bronchogenic carcinoma (author's transl)].

Selective bronchial angiography and short term intra-arterial infusions of Mitomycin C were performed in 70 patients with bronchogenic carcinoma. The courses were given 1--5 times with a median interval of 2 weeks. The angiograms were compared with chest radiograms and data obtained at bronchoscopy, mediastinoscopy, surgery or autopsy. The effect of therapy was evaluated with chest radiography and bronchoscopy. Among our first 36 patients an objective response was registered in 18/27 patients with squamous cell carcinoma, in 4/7 with adenocarcinoma and in 2/2 with small cell cancer. These results warrant further studies. Though not suitable as a routine procedure in the diagnostic work up of a patient with possible bronchogenic carcinoma bronchial angiogrpahy may contribute to a better staging when used e.g. in connection with intraarterial chemotherapy.


Mammalian endogenous peroxidases as cellular markers and as biosynthetic endpoints of hormone-mediated activity: viewpoint from cytochemistry.

Aldehyde-resistant, diaminobenzidine-stained endogenous peroxidases form ideal markers for the biochemical endpoints of hormone stimulation and differentiation of certain mammalian cells and tissues. The lactoperoxidase (LPO)-type of endogenous peroxidases are synthesized by the acinar cells of the salivary, Harderian, lacrimal and mammary glands and are present in their secretions. These LPO-type enzymes, that are inhibited by cyanide and aminotriazole, appear to operate extracellularly as bactericidal agents in milk and in other biological fluids. In the mammary gland, lactoperoxidase is a consistent marker enzyme for differentiated acinar cells engaged in lactogenesis. Myeloperoxidase (MPO)-type endogenous peroxidases are prominent markers for the GERL endomembrane system and differentiated lysosomes in certain cells of the reticuloendothelial system and phagocytes. MPO is prominent within eosinophils, peritoneal macrophages and in Kupffer cells. The MPO-type endogenous peroxidases function primarily within lysosomes as bactericidal agents. Thyroid peroxidase (TPO) is relegated to the cisternae of the granular endoplasmic reticulum and Golgi apparatus, to apical cytoplasmic vesicles and to the luminar cell membrane surface of acinar cells. The enzyme is probably activated at release and functions both in the organification reaction (T leads to To) and in the biosynthesis of thyroxine. Thyroid stimulating hormone (TSH) appears to play a key role in the regulation of TPO levels and activity in the thyroid gland. Certain tissues displaying growth-dependency on estrogen (i.e., uterus, cervix, vagina and the DMBA-induced rat mammary tumor) synthesize and secrete endogenous peroxidase into their lumina. These enzymes serve as important marker proteins of estrogen action, in that they occur distal to the binding of estrogen to its receptor protein. Estrogen antagonists, particularly CI-628 (Parke-Davis) and Nafoxidine (Upjohn) that appear to function through the estrogen receptor mechanism, also induce synthesis of the reproductive tract endogenous peroxidase but inhibit growth of these tissues. Progesterone antagonizes the synthesis of the reproductive tract peroxidases and inhibits growth of the tissues as well, in part, through the reduction of the cytosol estrogen receptor protein. Endogenous peroxidase activity appears to represent a reliable marker for rodent breast cancer tissues displaying dependency for estrogen and is of potential interest as a diagnostic marker protein in human breast cancer. Rat uterine peroxidase (UP) has been investigated by microelectrophoretic techniques. The molecular weight of UP has been determined in the range of 100,000 by using polyacrylamide gradient gels in the absence and presence of nonionic and anionic detergents. The isoelectric point of UP is located between pH 4.5 and 5.9. Employing the two-dimensional combination of isoelectric focusing and gel gradient electrophoresis, UP was separated into two subunits, one having a molecular weight of 70,000, the other less than 20,000.


Effect of alcohol on the plasma cAMP response to glucagon.

Prior studies indicated that acute ethanol feeding induced a decrease in adrenergic sensitivity as measured by the plasma cAMP response to isoproterenol. In this report we show that two hours after acute ethanol ingestion the plasma cyclic AMP levels were increased 8.5 fold 6 minutes after glucagon injection. Saline controls showed a 35 fold increase in plasma cAMP levels after glucagon injection. It is suggested that the decreased response caused by ethanol may be due to a decrease in the sensitivity of glucagon receptors.


Comparison of duration of immunity in chickens infected with a live infectious bronchitis vaccine by three different routes.

Three groups of chicks were vaccinated by aerosol, intra-ocular and drinking water routes with a live infectious bronchitis (IB) vaccine. At one, two, six, 15 and 32 weeks after vaccination five birds from each group were sampled for testing for IB haemagglutination-inhibiting (HI) antibodies and challenged. Assessment of susceptibility to infection was measured by recovery of virus from individual tracheas and from kidney and gonad pools four days after challenge. Virus was isolated from all kidney and gonad pools of birds challenged one week after vaccination, the kidney and gonad pools of the drinking water vaccinates at two weeks, the kidney pool of the intra-ocular group at 15 weeks and all organ pools except the gonads of the intra-ocular group at 32 weeks. Tracheal resistance was found in most of the birds challenged one week after vaccination and in all the birds tested at two weeks but had begun to wane by six weeks after vaccination. No correlation was found between low HI antibody titres of individual birds and their susceptibility to challenge measured by reisolation of virus from the traches, but birds with titres over log2 6 were always resistant.


Airway response to adrenergic agonists and antagonists in 3-day- to 2-year-old rats.

The response of the airways to adrenergic agonists and antagonists was studied in 3-day- to 2-year-old and bronchitic rats. The results showed that the alpha-adrenoceptors are not functional at birth but become so by 8 weeks. In contrast, the beta-adrenoceptor effects are demonstrable on the third day after birth. The mean decrease in airway luminal diameter after beta-adrenergic blockade was greater in bronchitic than in healthy animals and was interpreted to be due to the increased sensitivity of the beta-adrenoceptors in bronchitis.


[Studies of the proteins in normal bronchial secretion].

Parallel determinations were made, of 10 individual serum proteins and of proteins in the bronchial secretion obtained by aspiration from 8 subjects that did not show manifest bronchopulmonary disease. By application of the formula suggested by Deuschl and Johansson it was found that 37 percent of IgG, 84,5 percent of IgA, 48,9 percent of transferrins, 15,2 percent of alpha-1-anti-trypsin and 11,3 percent of ceruloplasmin present in the bronchial secretion are synthetised in the bronchial mucosa itself, while the rest occur as a result of diffusion from the blood. Acid alpha-1-glycoprotein and haptoglobin from the bronchial secretion originate in the blood. IgM was evidenced in the bronchial aspirate in only 3 subjects, and alpha-2 macroglobulin was not found in any of the subjects.


[Adverse reactions to antitubercular treatment with rifampin (Considerations on 14 cases].

An analysis of a group of 120 patients with pulmonary tuberculosis undergoing rifampicin treatment attempted to perform a study of adverse reactions induced by this drug used in modern therapeutic regimens of short duration (6 to 9 months). This was prompted by the increasing number of papers in the specialized literature concerned with such adverse reactions that occur in 10--50 percent of all cases treated with rifampicin. Adverse reactions to rifampicin (influenza-like syndrome, digestive syndrome, hepatic syndrome) were relatively rare in the group presented here (11,8 percent), when compared with the data in the literature. Although no severe adverse reactions occured, suppression of rifampicin therapy was necessary in most of the cases, and this modified the efficiency of the treatment. This low incidence has however a statistical significance indicating that larger groups should be investigated.


[Virological diagnosis of enteroviral diseases].

68 human enteroviruses are responsible for many acute viral diseases. An economic diagnostic procedure is discussed and documented by the author's own findings. Virus isolation is regarded as the method of choice, for epidemiological reasons and in view of the fact that enteroviruses are often isolated within a few days.


[Recurrent bronchopulmonary infections due to humoral immune deficiency].

Between 1974 and 1978 11 patients were detected, in a pneumology department. They were classified as follows: stage I, with relatively benign bronchial infections; 5 patients were included in this group, all of them made uneventful recoveries, without sequellae; stage II was characterised by more severe infections, that required repeated hospitalisation. Five more patients were included in this group. The patients in these two stages had either selective IgA deficiencies or combined (IgA and IgM) deficiencies. In stage III the disease had a severe evolution, characterised by extensive pulmonary tissue destruction and permanent suppuration. One patient had agammaglobulinemia in which the deficiency of serum and secretory bronchial immunoglobulins was complete. Although immunoglobulins represent only a part of the defense mechanisms of the respiratory pathways, their dosage is however recommended in all cases in which anamnesis, symptomatology or the evolution of the disease suggest the possibility of selective or total immunoglobulin deficiencies.


[The effect of lipid level lowering diets on bile lipids and plasma lipoproteins in normal persons].

The effects of two fat-modified diets, one rich in polyunsaturated and the other in oleic acids, were studied in 10 healthy young males with regard to bile lipid composition, plasma lipids and lipoproteins. The two experimental diets were given for 2 weeks each and findings compared with those from the subject's normal diet. The fat-modified diets had marked but comparable effects on plasma total cholesterol (decreases by 23% and 16% respectively), on LDL-cholesterol (decreases by 27% and 17% respectively) and on HDL-cholesterol (decreases by 26% and 27% respectively). HDL apolipoproteins A-I and A-II were unaffected. Therefore, the apo A-I/HDL-cholesterol and apo A-II/HDL-cholesterol ratios significantly increased. The "lithogenic index" as a measure for the relationship of cholesterol to bile acids and phospholipids, and thus for the solubility of cholesterol in gallbladder bile, was not affected by the lipid lowering diets, which therefore should not increase the risk of cholelithiasis.


Clinical and etiological heterogeneity of idiopathic diabetes mellitus. The banting memorial lecture.

We have presented and reviewed evidence for the heterogeneous nature of diabetes mellitus in terms of genetics, environmental factors, insulin responses to glucose and vascular disease. We have reviewed evidence for heterogeneity between juvenile-onset diabetes (JOD) and maturity-onset diabetes (MOD) and maturity-onset diabetes of young (MODY) and for heterogeneity within groups of JOD and MOD and MODY patients. Although much remains to be learned, a beginning has been made and suggests that primary diabetes mellitus is not a single specific disease but a syndrome comprised of a variety of diseases all characterized by hyperglycemia and tissue changes that result from heterogeneous etiologic and pathogenetic factors. Future classifications of primary diabetes mellitus will undoubtedly be lengthy, as are for other diseases and syndromes also caused by a variety of etiologic and pathogenetic mechanisms.


[Retrospective study of 149 cases of hepatitis B virus infections. Study of markers and of evolution].

A retrospective study has been performed in 149 subjects with present or past HBs antigenemia. The group consisted of 8 asymptomatic carriers, 90 with acute hepatitis, 7 with fulminating hepatitis, 27 with chronic hepatitis, 16 with cirrhosis and 1 with hepatoma. The changes from one clinical condition to another, the sources of infection, the percentage of acute hepatitis in the history of chronic hepatitis cases and the working capacity an average of two years after the infection were studied. HBe antigen and the corresponding antibody were detected by immunodiffusion and the results compared with the clinical course.


[Clinical aspect of herpes zoster and the pathogenesis of symptomatic cranial nerve zosters].

The prognosis of shingles is generally good, however if cranial nerves are affected, the course of disease may be very serious. It is still doubtful if latent virus-in the sense of a trigger mechanism-may be activated by dental surgical interventions and cause a symptomatic herpes zoster of cranial nerves. Serious loss of teeth as an oral manifestation of shingles, with panostitis and retarded healing show the seriousness of the tissue changes. The virus can invade the plexus between the facial and trigeminal nerves and can thus travel within the same epineural sheath from one nerve to the other. It follows that in each case of a herpes zoster of cranial nerves, irrespective of location, no dental surgery should be undertaken, even in the initial stage, because - it may increase the extension of the disease along the nerves - it may cause a viraemia - it may initiate uncalled for intraoperative and postoperative complications. Therapy with high doses of antibiotics is indicated.


[Cervical syndrome].

The cervical syndrome is described and the possibility of facial pain. Pathologic changes in the anatomical buildup of the cervical spine with its nerve and vascular systems may cause symptoms which may not be recognized for their relationship to the cervical spine. There are no anatomical nervous connections between the maxillofacial and the cervical region, and yet there is evidence of maxillofacial pain caused by cervical factors. The dentist must often answer questions of this nature. The therapy of cervical disease is difficult and requires knowledge, experience and intuition from the treating physician.


Killing of fibroblasts by dexamethasone or dibutyryl adenosine 3',5'-monophosphate is not a valid test for cystic fibrosis.

Assays based on the counting of total cells and of colony-forming cells were used to demonstrate that neither dexamethasone nor dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) kills human fibroblasts under a variety of conditions. These results contradict those of previous studies showing that dexamethasone and dibutyryl cyclic AMP kill a higher percentage of fibroblasts from normal humans than from individuals with cystic fibrosis.


[Study of blood glucose regulation in 103 cases of adult acquired hypothyroïdism (author's transl)].

Systematic studies of blood glucose regulation have been performed in 103 cases of adult acquired hypothyroïdism. The results were the following: 11 cases of overt diabetes were discovered. The diagnostic was made when fasting blood glucose was superior to 120 mg/100 ml and glucosuria was present. 22 cases of asymptomatic (chemical) diabetes. The diagnosis was based on the abnormalities of the oral glucose tolerance test (OGTT). The criteria were those of Fajans and Conn. In 70 cases the results were normal. The comparison of these results with these obtained in a matched population of normal subjects did not show significative differences. Particularly the proportion of "flat curves" during the OGTT were not higher in cases of hypothyroïdism. Plasma insulin levels were determined in 20 cases of hypothyroïdism during OGTT. The results were the same as in non-hypothyroïd subjects. The abnormalities of glucose regulation observed in hypothyroïdism were not related to sex, age, overweight or cause of the disease. The number of diabetic patients is not significatively more important in cases of hypothyroïdism of immunological origin (especially Hashimoto's disease.


[Association of scleroderma with primary biliary cirrhosis (author's transl)].

A new case of Reynold's syndrome is reported. This patient was a 70 years old woman with scleroderma (grade II) and PBC (grade III - IV), associated with Sjögren's syndrome and cryoglobulinemia. She experienced 10 years earlier Raynaud's syndrome and arthralgia. A review of the Literature reveals 22 other detailed cases whose data are collected in this study. Considerations upon a common pathophysiology for scleroderma, PBC and Sjögren's syndrome are developed. Impairment of the function of suppressor T cells in patients undergoing these diseases is possible.


[The primary neoplasm of the gall-bladder. Report of 55 cases (author's transl)].

The authors report 55 cases of primary neoplasms of the bladder which represent 5,2 per cent of cholecystectomies, their study prove its very important deadly character. They insist on the necessity of the immediatly systematic examination. This examination permit a knowledge of the in situ stades and permit to make adapted surgical treatment. This treatment may be a cholecystectomy if it's a in situ type adenocarcinoma but it must be an enlarged cholecystectomy in all the other cases.


[Bone and calcium metabolism in adult hypothyroidism (author's transl)].

A study of blood and urinary calcium and phosphorus, 25 hydroxyvitamin D plasma level (25 OH D3), bone radiology and hystology is performed in 12 hypothyroïd adult patients. This study confirms the notion of myxoedematous ostéopetrosis. Radiologic and histologic findings shows an osteocondensation, more important on the skull, and augmentation of cortical thickness of the bones is noted. Quantitative histologic findings, shows some signs of diminution of bone cellular activity. Low plasma level of 25 OH D3 in these patients is discussed in the view of an event of a disturb in the metabolism of D-vitamin in hypothyroïdism.


[Clinical test in current psychopathologie (author's transl)].

This clinical test, concerning the use of tiapride, was carried out for one year on 60 patients, with weekly or bi-mensual check-ups in a neuropsychiatric office, with no other associated medication capable of modifying either vigilance or humor. Tiapride, on top of its excellent tolerance (except for patients presenting a hysterical type structure), and apart from being a sedative for anxiety, turned out to be, on one hand, a disinhibitor for states of depression (even more so when accompanying psychosomatic symptomatology was apparent), and on the other hand a semeiological analyser inasmuch as it can help discern the underlying psychopathological structure.


[Acute intoxications by tricyclic antidepressants (author's transl)].

The authors report 87 cases of acute voluntary intoxications with tricyclic antidepressants. They essentially studied the cardiac complications; and conclude that the prognosis is more severe than for other intoxications.


[Hereditary dysfibrinogenaemia. Study of a family (author's transl)].

This note studies fourteen members of the same family over three generations. Ten of them have biological dysfibrinogenaemia without haemorrhagic diathesis or thrombosis. The diagnostic is essentially based on the study of fibrin formation by thrombine time. On the other hand global coagulation tests are little or not at all disturbed and the rate of physiologically active fibrinogen is sometimes subnormal. The biological outline of the defect is superposable to the one of the majority of hereditary dysfibrinogenaemia cases actually published. The classical prevailing autosomal transmission is confirmed.


[Study of some immune functions in cardiac patients undergoing an extra-corporeal circulation operation (author's transl)].

61 adult patients (36 men, 25 women), with coronary or valvular diseases, operated with extra-corporeal circulation, by the same surgical team, have been investigated for the plasmatic levels of total complement, fractions C4, C3 activator, C3, immunoglobulins G, A and M, for the phagocytic and bactericidal activity of polymorphonuclear leucocytes. 50 healthy adults (26 men, 24 women) have been tested as controls. Results have been statistically analyzed. Two experiments have also been performed: extra-corporeal circulation machine has run alone without a patient, and the examinations of blood samples in the machine have been performed before and at the end of the running time. Just at the end of extra-corporeal circulation, a deep and significant falling of globulins (complement and its fractions, immunoglobulins) is observed, which lasts during two days; at the 8th and 15th days after the operation, a significant and important raising of these globulins is noted. It has been demonstrated that the initial falling is not correlated with the hemodilution, but is relevant to a consumption in the machine and in the tissues. Any significant variation in polymorphonuclear leucocytes activity has not been noted, but there are strong individual variations. Importance of humoral abnormalities observed is discussed, regarding to the infectious prophylaxis in cardiac surgery.


[Therapeutic advances in geriatry. A report on 47 cases (author's transl)].

A group of 47 elderly patients with various ailments and aged between 66 and 99 years were treated with tiapride: very good results were obtained in 7 cases of severe buccofacial dyskinesia, though the dosage had to go as high as 800 mg/day; results were excellent in 2 cases, good in 9, moderate in 5, and nil in 3 out of 19 patients with agitated states; overall results were good (1 failure) in 8 cases of alcoholism (4 acute and 4 chronic); 8 good results and 4 failures were noted in 12 patients with either cancer pain, or pain following zoster or due to arthrosis or migraine. The product was very well-tolerated by these elderly patients.


[Enteral feeding in burn patients].

The deleterious effects of denutrition, both generally and locally, in the development of extensive burns are widely known. These can be corrected either by reducing the nutritional loss or by increasing the intake. As far as the loss is concerned, the burned area may lead to a veritable "calorific haemorrhage", arising in cases where more than 30 to 40% of the body surface is affected. Nitrogen loss occurs in the urine, from the digestive tract, or from the burn itself, and in a 70 kg subject with a 40% burn, it can reach 40 g of nitrogen. This loss can be compensated in four ways: -- though this presents difficulties the oral route; -- the parenteral route; but intravenous feeding is often insufficient or dangerous; -- discontinuous enteral feeding; but this is poorly supported by the patient, badly assimilated, and dangerous; -- low-rate continuous enteral feeding (LRCEF) which is the preferred method. Use is made of continuous flow-rate pumps, which can be regulated and refrigerated (fig. 1). The solutions (fig. 2) are prepared as required and 2 to 3 litres are administered continuously throughout the 24 hour periods. Regular observations are made: -- daily for weight, urine output, blood and urine electrolytes, blood nitrogen and sugar; -- weekly, for protein and lipid electrophoresis. The results obtained during 3 periods (1973, 1975 and 1977) are reviewed.  -- 1973 (19 patients, fig. 3). A cautious attitude prevailed and only one case of a positive cumulative result was noted. The total quantity ingested was never greater than 4 000 calories or 224 g of protein. There were quite a few incidents (fig. 4), and 45 "accident days" were reported. -- 1975 (13 patients). The nitrogen balance was occasionally positive. Cumulative results were obtained in 8 cases. There were 26 "accident days". Improvement was due to: . prompter recourse to LRCEF, . a more rapid progression in the amount given, . an increase in the maximum quantity, . increased water intake. These results led to the development of the present-day procedure which includes: . a preliminary tolerance-testing period of 8 days, during which intake is increased to 4 000 calories and 25 g of nitrogen, . a second period during which intake is adjusted to losses, with supplementary feeding by the parenteral or oral routes. -- 1977 (36 patients including 18 on water-beds). Better tolerance to the increase in the amounts ingested was recorded in the patients treated on a water-bed. This led to an increase in calories and nitrogen being given to these patients, who also seemed to have a greater ability to make use of the supplementary nitrogen. The use of LRCEF and water-beds, combined, needless to say, with the earliest possible covering of the burned skin area, make a substantial contribution to the reduction of losses in burn patients.


[Principles underlying the use of antituberculosis medication in children (author's transl)].

The authors review the principles underlying antituberculosis therapy in children. Basing their comment on the published literature, they analyze the properties, pharmacology, toxicity, and side-effects of each medication, and define their dosage and modes of administration.


[Peritonitis by ruptured pyonephrosis (author's transl)].

The authors have observed one case of peritonitis by ruptured lithiasis pyonephrosis. The elective treatment of this unusual (13th case in the literature) complication of the urinary lithiasis is the nephrectomy.


Traumatic hypopituitarism: anterior hypophyseal insufficiency from indirect cranial trauma.

We have reported a case of partial hypopituitarism involving deficient ACTH, LH, FSH, and growth hormone production and elevated prolactin. The hypopituitarism was caused by injury to the pituitary resulting from a parachute accident without direct craniocerebral trauma. The pathogenesis of this pituitary injury as either a clivus fracture near the sella, unilated abstruction of the internal carotid artery, and/or direct stalk injury. Clinicians should be alerted to the possibility of hypopituitarism from direct or indirect cranial injuries.


[Transfusional malaria. Another case (author's transl)].

Transfusional malaria is an unusual disease. Any fever, happening immediately after blood transfusions must evoke this diagnosis, confirmed by parasites detection in the blood. The treatment is rapidly efficacious. The prophylaxis is at the present time insufficient and would require fluorescent antibody test generalization.


[Anatomical and clinical features of a case of gall-bladder abnormality. Results of arteriographic and micro-angiographic studies (author's transl)].

The authors describe a perplexing clinical picture in which an important factor for diagnosing the lesion in the gall-bladder was hyperselective arteriography of the coeliac trunk, and more especially the hepatic artery. The association of a truc septum in the gall-bladder, without gall-stones, and of another digestive tube lesion, megadolicho-sigmoid and diverticulosis of the sigmoid, would appear to be an extremely rare entity, and this has been the cause of the pain reported by the patient over many years. The cholecystectomy performed appears to be the right choice, and the most effective therapeutic procedure.


Inhibitory effects of non-steroidal anti-inflammatory drugs on human myeloperoxidase.

Myeloperoxidase with an A420/280 ratio of 0,48 was prepared from normal human leucocytes. This partially purified preparation catalysed guaiacol oxidation, iodination of bovine serum albumin and de-iodination of 125I-thyroxine. Non-steroidal anti-inflammatory drugs (naproxen, indomethacin and flufenamic acid) showed a significant inhibitory effect on myeloperoxidase-catalysed iodination at concentrations of 10(-4)M and higher. Guaiacol also inhibited myeloperoxidase-catalysed iodination, and its iodination inhibition curve was nearly identical to that obtained with the anti-inflammatory drugs. At concentrations between 10(-3)M and 10(-7)M the antiinflammatory drugs had very little or no effect on thyroxine de-iodination. Flufenamic acid and indomethacin, however, inhibited de-iodination significantly at a concentration of 10(-2)M. It is postulated that non-steroidal anti-inflammatory drugs may inhibit myeloperoxidase-catalysed protein iodination by acting as oxidizable cofactors which compete with other oxidizable substrates for oxidants formed by the peroxidase-hydrogen peroxide complex. In view of this and because the myeloperoxidase-hydrogen peroxide system may be involved in inflammatory tissue damage, the possibility should be considered that the action of non-steroidal anti-inflammatory drugs is at least partly attributable to a radical scavenging effect or to sequestration of oxidants.


Cardiac myofibrillar phosphorylation and adenosine triphosphatase activity.

When myofibrils from rat hearts were dissolved in concentrated salt solutions and reprecipitated by dilution, they contained both protein kinase (partly cyclic 3':5'-AMP-dependent) and protein phosphatase activities. Troponin-I was the major protein to be phosphorylated by the endogenous myofibril-associated kinase and by added protein kinase. Approximately 1 mole of phosphate per mole of troponin-I was incorporated from radioactive ATP, but the extent of troponin-I phosphorylation could be varied experimentally. An inverse correlation was found between protein phosphorylation and the maximum Ca2+-stimulated myofibrillar Mg2+-ATPase activity, while the amout of calcium required for half-maximum activation was proportional to the extent of protein phosphorylation. The changes in Mg2+-ATPase activity produced in vitro by protein phosphorylation were reproduced in isolated perfused rat hearts treated for short periods with L-noradrenaline (10(-6)M). The changes in myofibrillar function brought about as the result of the phosphorlyation by cAMP-dependent protein kinase suggest that the contractile response is desensitized in order to cope with the rise in intracellular Ca2+ which results from the action of catecholamines on cardiac ventricular cells.


Liver tumours and the contraceptive pill: Controversies in aetiology, diagnosis and management.

Six female patients seen at Groote Schuur Hospital between 1973 and 1977, with the types of liver lesion that have been linked aetiologically with the contraceptive pill, are described. Four had focal nodular hyperplasia (1 with spontaneous rupture), and 1 patient had a hepatocellular carcinoma. The sixth patient had spontaneous rupture of the liver but no tumour was demonstrated. Based on this experience and a review of the literature, controversies in aetiology, diagnosis and managment are presented. A defined management policy is proposed for the benign lesions, a less aggressive approach being advocated for focal nodular hyperplasia than for hepatic adenoma.


Preoperative radiotherapy and chemotherapy in hypervascular, high-grade supratentorial astrocytomas.

From a group of ten patients with hypervascular, high-grade, supratentorial astrocytomas, five were treated with pre-operative radiotherapy alone, and five with radiotherapy in combination with cytostatic drugs. The aim was to investigate the timing of intracranial operations in the multimodality therapy of brain tumors. The tumor size was diminished only in one case, but tumor vascularization was reduced in half of the cases by the pre-operative treatment. Survival was not improved. Surgical treatment still should be the first of the therapeutic measures. Pre-operative radiotherapy may be of value to reduce tumor vascularization in hypervascular, centrally localized tumors.


Mixed malignant tumour of the lung.

A mixed malignant tumour of the lung intermediate in type between pulmonary blastoma and carcinosarcoma is described. The epithelial component consisted of squamous carcinoma, undifferentiated carcinoma, and clefts lined by bland epithelial cells. The supporting stroma was composed of pleomorphic sarcoma, fibrosarcoma, chondrosarcoma, osteosarcoma, and indeterminate mesenchymal tissue. The tumour was removed surgically, but the patient died postoperatively with rapidly developing multiple bony and soft tissue metastases. Subcutaneous metastases showed the appearnce of poorly differentiated pleomorphic sarcoma. Published reports of mixed malignant lung tumours are reviewed.


Inhibition of electrogenic sodium transport across toad urinary bladder by the mycotoxin patulin.

The effects of the mycotoxin patulin (4-hydroxy-4H-furo[3,2c]pyran-2(6H)-one) on short circuited intact toad bladder and on Na+-K+, activated ATPase were examined in an attempt to elucidate the relationship between toxin, the Na+-K+ ATPase enzyme system and associated active sodium transport. Patulin inhibited transbladder short circuit current and Na+-K+ ATPase from isolated bladder preprations. The effect was exponentially dependent on time. A significantly slower rate of inhibition was achieved within 15-30 min. The results are compatible with the assumption that Na+-K+ ATPase is associated with the pump mechanism since patulin inhibited enzyme activity and concomitantly reduced the rate of electrogenic Na+ transport. A significant correlation suggested a cause-effect relationship.


Silicosis and fibrogenesis: fact and artifact.

Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis.


Urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate. Significance of proportionate differences during the menstrual cycle.

The urinary excretion of estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate in men and throughout the menstrual cycle in women was measured by specific radioimmunoassay. In 9 men the mean +/- SE excretion of these conjugates was 15.9 +/- 1.4, 2.7 +/- 0.3, and 3.2 +/- 0.2 microgram/24 h respectively. In 15 women studied in the midfollicular phase (day 8) of the menstrual cycle, the excretion was 19.4 +/- 1.7, 2.9 +/- 0.2, and 5.4 +/- 1.3 micrograms/24 h. Excretion of each conjugate was significantly (P less than 0.01) elevated in the midluteal phase (day 22) to 41.9 +/- 3.9, 6.3 +/- 0.8, and 12.2 +/- 1.5 micrograms/24 h respectively (n = 14). The mean excretion of estriol-16 alpha-glucosiduronate was greater than that of 17 beta-estradiol-17-glucosiduronate in the luteal phase (P less than 0.05) but not in the follicular phase or in men (P greater than 0.05). The excretion of each of these specific conjugates measured throughout the menstrual cycle in 7 women was characterized by a sharp midcycle peak and a lower, broader luteal phase peak. The ratios of estriol-16 alpha-glucosiduronate to 17 beta-estradiol-17-glucosiduronate, estrone glucosiduronate to 17 beta-estradiol-17-glucosiduronate, and estriol-16 alpha-glucosiduronate to estrone glucosiduronate throughout the menstrual cycle were analyzed. When the mean ratio during the follicular phase was set at 1, a significant increase (P less than 0.01) occurred in the mean luteal phase ratio in each case: 1.00 +/- 0.03 to 1.66 +/- 0.09, 1.00 +/- 0.04 to 1.30 +/- 0.04, and 1.00 +/- 0.03 to 1.24 +/- 0.04 (mean +/- SE) respectively. The marked alteration in the proportions of these urinary estrogen conjugates may be due to altered metabolism of 17 beta-estradiol, but it more likely reflects a change in the pattern of estrogen secretion or production between the two phases of the menstrual cycle.


Dexamethasone suppressibility of plasma pregnenolone or dehydroepiandrosterone in gonadectomized patients.

The 9 AM dexamethasone suppression test was carried out in gonadectomized patients, and plasma pregnenolone or dehydroepiandrosterone (DHA) was radioimmunoassayed following various amounts of dexamethasone administration. Pregnenolone, as well as the plasma ACTH level, was completely suppressed with 1 mg dexamethasone, whereas 4 mg or 8 mg of dexamethasone was needed to induce a complete DHA suppression. These findings suggest that the gonads alone contribute to the poor dexamethasone suppressibility of pregnenolone in normal subjects, and that adrenal DHA secretion might be also regulated by an unidentified factor other than ACTH, which would be suppressed with large doses of dexamethasone.


Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.

Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.


[Phosphonates and their importance for dental practice].

In the light of a literature review, the author deals with the significance of anorganic pyrophosphate in the mineralization process in the organism. Diphosphonates are synthetic substances which act on mineralisation. The author made experiments with them, the results of which might be of importance in the stomatological sphere with regard to caries reduction and plaque inhibition.


Effect of primary and recurrent cytomegalovirus infections upon graft and patient survival after renal transplantation.

One hundred sixty-four patients were prospectively studied for evidence of cytomegalovirus (CMV) infection after renal transplantation to determine the effect of primary and recurrent CMV infection on early graft and patient survival. Primary infections occurred in 62% (21 of 34) of pretransplant seronegative recipients and recurrent infection infection in 93% (121 of 130) of seropositive recipients. Symptomatic infections occurred in 81% (17 of 21) of primarily infected and 31% (37 of 121) of recurrently infected recipients. CMV infections (determined by initial virus excretion) occurred in 86% of the primarily infected and 96% of the recurrently infected symptomatic recipients by the 9th post-transplant week. In contrast, only 53% of nonsymptomatic recipients excrete virus by the 9th week. Primarily infected recipients experienced a significantly lower graft survival at 6 months than uninfected seronegative or recurrently infected patients. However, there was no significant difference in patient or graft survival at 1 year. Recipients who developed recurrent symptomatic infections had a significantly lower graft and patient survival than those recipients who developed nonsymptomatic recurrent infections (P less than 0.0002 patient survival and P less than 0.001 graft survival at 12 months).


Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival.

Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion.


Prospective study of the prevalence and symptomatology of cytomegalovirus infection in renal transplant recipients.

To determine the incidence and symptomatology of cytomegalovirus (CMV) infection in renal transplant recipients, we followed 40 patients prospectively for 5 to 24 months after operation. As judged by the serological change and virus isolation from blood and/or urine, the infection rate for the entire group was 82% (33 of 40 patients). Two types of infection were recognized: primary infection that occurred in 3 patients, and reactivation infection that occurred in 30 patients. Twenty-one patients were asymptomatic and 12 were mildly symptomatic. Four had mild hepatic dysfunction; two had the CMV mononucleosis syndrome associated with mild to moderate deterioration of renal function. Two patients had hyperglycemia. One patient who reached a CMV antibody titer of 1:32,768 was totally asymptomatic other than fever of short duration. CMV-induced pneumonitis or retinitis was not noted, and there was no mortality from CMV infection in our patients. Factors which may be associated with the absence of severe manifestations of active CMV infection in these patients are discussed.


[Dynamics of the spreading of normal and transformed hamster cells].

Morphological peculiarities of spreading studied by scanning electron microscopy in two lines of transformed hamster fibroblasts (HETR and HEC--40) were compared to the normal hamster embryo fibroblasts (NHG). The surface of spherical not streading cells was of a mixed type microrelief (small blebs and microvilli). In transformed cells, the microvillous component was more developed than in their normal counterparts. During cell spreading distinct differences were observed between normal and transformed cells in their cell surface contact interaction with solid substratum. NHF cells formed a well-developed concentrically disposed thin lamelloplasm, while HEC-40 cells had asimmetrically disposed lamelloplasm in combination with long filopodia and HETR cells had a rather thick lamelloplasm consisting of several fragments (often forming star-like pattern). At the polarization stage of spreading neither HETR nor HEC-40 reached the same degree of spreading and flattening as NHF. Moreover, the dorsal surface of transformed cells had a complex microrelief in contrast to a rather smooth surface of NHF. These results are discussed in connection with earlier results on spreading of normal and transformed mouse fibroblasts.


[Effect of a viral infection on the cellular chromosome apparatus of mice in vitro and in vivo against a background of hydrocortisone action].

A cytogenetic investigation of murine bone marrow after hydrocortison injection has been made. High doses of hormone (50 mg/kg) provoke deteriorations in bone marrow both in the structure and in the chromosome number. A dose of 5 mg/kg has no such effect. The Koksak A13 virus does not induce cytogenetic deteriorations in mice, however, it is able to produce a big mutagenic effect on the hydrocortison background. The vaccine strain of measles virus -- Leningrad-16 -- also increases its mutagenic action on the bone marrow cell chromsome apparatus of mice affected with hydrocortison. At the same time, in the cell culture of murine kidney, hydrocortison does not induce chromosome deteriorations and even lowers the frequency of cells with deteriorations in the chromosome set during the initial days after injecting the virus culture with measles virus.


Ultrastructural study of leukemic cell phagocytosis using the myeloperoxidase reaction.

The phagocytosis (in the absence of serum factors) of zymosan particles by peripheral leukocytes isolated from ten patients with acute leukemia (AMbL, AMoL, AMML, AUL, ALL and CML-BC) was studied at the electron microscope. An evident phagocytic activity was observed only in the cells in which cytochemical and ultrastructural features suggested that the blast elements belonged to the monocytic series. However, no phagocytosis by unclassifiable leukemic blasts was observed, even though they had some submicroscopic characteristics of the monocytic series. These findings suggest that phagocytic capacity develops during the course of cell differentiation, becoming striking only when the blast cell acquires the ultrastructural features of the pro-monocytic stage. Using the myeloperoxidase reaction, this study also demonstrates a morphological alteration in the degranulation process after the ingestion of zymosan particles in both the blasts and the mature PMN cells of leukemic patients. This defect could be related to the susceptibility to severe infections usually found in subjects with hematological malignancies.


Early detection of ductal breast cancer: the diagnostic procedure for grouped microcalcifications.

Mammography and xeroradiography for grouped microcalcifications are considered the most effective diagnostic methods to detect occult breast carcinoma. Radiography must direct the surgeon to excise the nonpalpable area. The removal of the tissue with grouped microcalcifications must be confirmed by intraoperative radiological control. The histologic preparation must be guided by radiographic controls. Tissue with calcific deposits is examined by step sections. The diagnostic success depends upon the cooperation between the radiologist, the surgeon, and the pathologist. Our results from 1964 to 1977 have shown a frequency of 14.4% of occult carcinoma. Ductal or lobular carcinomata in situ have been diagnosed in 8.9%. In 9.9% of the patients, cystic disease with severe and atypical proliferations has been encountered.


Early detection of ductal breast cancer: the diagnostic procedure for pathological discharge from the nipple.

Pathologic discharge from the nipple may be the only symptom of an early stage of carcinoma. Galactography is then the diagnostic method of choice to locate intraductal, nonpalpable lesions. The technique of galactography, the adequate surgical approach of pathologic galactographs (milk-duct segment resection), and the appropriate histological work-up of the surgical specimen are demonstrated. We report on 1918 galactographies in 1363 women with pathological discharge. In only 427 cases was a milk duct segment resection necessary (31.4%). In 8.5%, we found invasive intraductal cancer and in 2.9% ductal carcinomata in situ. Only 1 patient with breast cancer had axillary metastases. Extensive intraductal solid, papillary or adenomatous proliferations were found in 11.9% of the patients with excision. In 46.7% of the patients, papillomas were excised, a definitive treatment for this process. The supposition for success in the early diagnosis of cancer is close teamwork among the radiology, surgery and pathology services: the diagnostic result depends upon this. We attribute our yield of exact diagnosis to a very sophisticated histological work-up. We believe that this is necessary to avoid diagnostic failures.


Lobectomy with bronchoplastic procedures for lung cancer.

From April 1970 to October 1977, 19 patients with lung cancer of the upper lobar bronchus orifice underwent radical lobectomy with major bronchus resection. Sleeve lobectomy was accomplished in 11 cases and wedge lobectomy in the remaining 8. The length of the free bronchial margin in the surgical specimen was less than 1 cm in 3 cases, but limited pulmonary reserve did not allow pneumonectomy. Squamous carcinoma was diagnosed in 14 patients, adenocarcinoma in 2, oat-cell carcinoma in 2, and large cell carcinoma in one. Most cases (70%) were pathological stage I. There was one operative death due to anastomotic leakage (5%), and another patient required pneumonectomy completion. Of 13 patients with non oat-cell carcinoma and adequate bronchial resection, none had local recurrence: 3 patients developed distant metastases, and 10 are alive and disease-free after a follow-up period ranging from 16 to 104 months. The authors conclude that in selected lung cancer patients lobectomy with bronchoplastic procedures is superior to pneumonectomy for tissue sparing advantages.


Unusual morphologic features of a primary liver neoplasm.

Light and electron microscopy study of an unusual primary liver neoplasm observed in a 36-year-old woman. By light microscopy the tumor, initially detected by a needle biopsy and later surgically removed, was mainly composed of spindle-shaped and multinucleated cells which were similar to rhabdomyoblasts. These cells, however, showed ultrastructural features of hepatocytes.


[Physicochemical and kinetic characteristics of myeloperoxidase of cow neutrophilic leucocytes].

Myeloperoxidase (MPO) isolated from granular fraction of cow peritoneal neutrophils had the RZ value equalled to 0.79. The absorption spectrum of MPO possesses characteristic bands at 430, 500, 570, 625, 690 nm. The molecular weight and sedimentation constant of the enzyme are 135.000-140.000 Daltons and 7.9S, respectively. The data obtained demonstrate the high thermostable property of MPO. Investigations of the pH optimum and effects of varying H2O2, o-dianizidine and MPO concentrations are described.


[Activity of certain redox enzymes of rat liver mitochondria at different levels of dietary vitamin E].

Taking into account the found earlier relation of vitamin E to the ubiquinone functioning and metabolism, the authors studied the enzymic activity of succinate dehydrogenase, NADH-dehydrogenase and cytochrome-c-oxidase--coenzyme Q binding sites of the respiratory chain of the rat liver mitochondria. The experiments were carried out with female rats who received a vitamin-E-deficient diet for 6 months. The enzymic activities and the ubiquinone content in the liver mitochondria of these animals are shown to be considerably lower as compared to the animals received a vitamin E diet; alpha-ocopherol, alpha-tocopheronolactone and ubiquinone 3h after administration manifest a clearly pronounced normalizing effect relative to both the enzymic activity and the ubiquinone content. An assumption is advanced that the effect of alpha-tocopherol and its metabolite is associated with controlling the level of functionally active ubiquinone in the mitochondria. Other mechanisms of the membrane-bound enzymes control by the compounds under study are also discussed in connection with the alpha-tocopherol effect on the mitochondrial membranes.


[Use of a selective sulfite-reducing medium for the isolation of Clostridium perfringens].

The effect of sulphite-reduction in 33 sample bacterial strains  was tested. With regard to the capacity of reducing sulphite in modified sulphite-reduction media in a wide scale of bacterial strains the possibility of an application of selective media with an addition of various concentrations of antibiotic solutions was checked. A concentration of 750 microgram of D-cycloserine per 1 ml of the sulphite-reduction medium appeared to be the most advantageous for the isolation and detection of sulphite-reductive clostridia, above all of Clostridium perfringens. This concentration ensured also a sufficient inhibition of undesirable bacteria without any affection of the growth and capacity of Clostridium perfringens to reduce sulphite in the applied medium.


[The effect of halothane anesthesia on the function of the adrenal cortex and some metabolites in the blood plasma of pigs not susceptible to malignant hyperthermia].

The effects were investigated of a 25-minute inhalation of halothane with oxygen on three to four months old pigs of the Large White breed. Symptoms of malignant hyperthermia did not occur. The actual total anesthesia, which causes slight hypoproteinemia, hypoglycemia and hypocholesterolemia without significant changes in the content of non-esterified fatty acids (NEFA) and urea, induced only a  slight increase of circulating 11-hydroxycorticosteroids (11-OHCS). The combination of anesthesia with castration of gilts or barrows significantly increased the concentration of 11-OHCS but did not reach the level recorded after the application of ACTH. The higher levels of 11-OHCS were accompanied by higher concentrations of NEFA and glucose. The treatment of the animals lasting half an hour prior to inhalation of halothane at maximum doses or one hour in the control unanesthetized pigs produced an effect, mainly on the 11-OHCS concentration and on the activity of creatine kinase in the plasma. The results indicate that the adrenocortical response to the effect of halothane is not stronger than the response to simple handling connected with excitement and muscular activity of the animals. Therefore there is no reason of considering halothane anesthesia as a factor causing great stress and pigs which in its course do not respond with malignant hyperthermia as animals insensitive to stress. The aptness of denotation of clinical manifestations of genetically defective muscles in pigs is discussed.