[Community health technical personnel].

[Community health technical personnel]. In this article the author describes his experience in training community health officers at the Community Health School of the State of Mexico. She presents her views on the training of this type of personnel to work in the rural areas of developing countries; described the fundamental characteristics of their training and the methods used; and indicates the difficulties encountered by the first graduates of the above-mentioned School when they took up their duties.


Blood fibrinolytic activity during major surgery in unsupplemented glucocorticoid-treated patients. Blood clot lysis time (BLT) and plasma cortisol concentration were measured during major abdominal surgery in 15 unsupplemented glucocorticoid-treated patients. Eight patients showed an impaired cortisol response and seven patients had normal cortisol concentrations when compared with the cortisol response of 23 control patients with normal pituitary-adrenal function. There was no statistically significant difference between variations of BLT in the group of patients with impaired cortisol response and patients with normal cortisol concentrations. It is concluded that stress-induced activation of blood fibrinolysis is coincidental with, but independent of, adrenocortical activity.


Energy transfer in photosynthesis.

Energy transfer in photosynthesis. A theoretical model is presented to account for the physical mechanism of energy transfer from antenna molecules to the reaction centers in photosynthesis. The energy transfer is described by a generalized transport equation or "master equation". The solution of this equation for the proposed model gives a relationship between the antennae interaction energy and the transfer rate. The results are shown to be in agreement with inter-antenna transfer rates calculated from experimental fluorescence lifetimes. Previous theories were based either on the Förster mechanism, which is valid for very small interaction energies, or an exciton model valid for very large interactions, but experimental results seemed to indicate that the actual situation was intermediate between these two. The Förster theory and the exciton model are limiting cases of the master equation.


Spectral properties of system I-deficient mutants of Chlamydomonas reinhardi. Possible occurrence of uphill energy transfer. Chlamydomonas reinhardi mutants lacking the P-700-chlorophyll alpha-protein complex CPl, lack as well the long wavelength forms of chlorophyll Ca 691 and Ca 704 normally present in the absorption spectrum at -196 degrees C. These mutants do not display the 715 nm peak in the fluorescence emission spectrum at -196 degrees C. Studies of the System II action spectrum of one such mutant show an increase in the optical cross-section of the System II centers around 685 nm. This is interpreted as an energy transfer from pigment System I to pigment System II occurring in the mutant.


Iodination of chloroplasts. I. Properties of iodinated chloroplasts. Spinach chloroplasts exposed to iodide can be washed free of the bulk of the iodide. In the presence of lactoperoxidase and H2O2, iodide can be introduced into chloroplasts in high amounts and in non diffusible forms. The resultant particles, which have been named iodochloroplasts, extrude their iodide upon stimulation by light. The form and the amount of extruded iodide bears a definite relationship to the amount of incident light. A flash of marginally effective light is additive to the next such flash even after a lapse of 10 min of darkness. These and other properties of iodochloroplasts may make them of great use in the study of intermediate reactions of photosynthesis.


Inhibition by ammonium chloride of the oxygen yield of photosynthesis. Flash O2 yield experiments are described in spinach chloroplasts and Chlorella after addition of NH4Cl. (1) The damping of the sequence is increased by NH4Cl. (2) The turnover times are accelerated but the reaction during which O2 is released (S3bv leads to S4 leads to S0) is slowed. (3) We observed between the end of the turnover kinetic and the beginning of deactivation a latency time tl during which the S2 and S3 states are perfectly stable. In the presence of NH4Cl, this latency time for S2 is shortened, diminishing from 1 s to less than 12 ms; whereas it is lengthened for S3 (up to 4 s, 5 s). (4) After this latency time, two phases are clearly distinguished in the S2 deactivation: the beginning of the deactivation is abrupt, varying like the square root of the time, i.e. as is characteristic of a diffusive process. During the second phase, S2 is stabilized. Our experiment shows that S2 deactivation is monitored by the release of some product F after the latency time from one particular locus, so that nearby Photosystem II reaction centers are rapidly deactivated by diffusion of the product, whereas centers far from this locus are very slowly deactivated. These results are qualitatively complementary to the luminescence experiments of Velthuys (Biochim. Biophys, Acta (1975) 396, 392-401) except for the latency time which is invisible in the Velthuys results. We propose a modified model in which the binding of NH3 on states S2 and S3 occurs during deactivation.


The I-D fluorescence transient. An indicator of rapid energy distribution changes in photosynthesis. The I-D transient in the chlorophyll fluorescence induction curve (kautsky effect) is investigated in the view of recently discovered rapid changes in energy distribution between the two photosystems (Schreiber, U. and Vidaver, W., FEBS Lett., in the press). Fluorescence induction curves differ appreciably depending on whether measured at lambda less than 690 nm, originating in pigment system II, or at lambda greater than 715 nm, which is in part from pigment system I. The differences occur as well in the rapid part of the induction curve (O-I-D-P) as in the slower P-S decay. Most significant changes in energy distribution are indicated in the region of the I-D dip, being induced by appropriate preillumination. The effect is studied by (a) comparing the individual fluorescence time courses at lambda less than 690 nm and lambda greather than 715, (b) plotting F less than 690 vs. F greater than 715 and (c) recording time courses of F less than 690/F greater than 715 ratios. In (a) the I and D characteristics are delayed at F greater than 715 relative to F less than 690, which is accompanied by periods close to I and D, where the two emissions follow inverse courses. In (b) the I-D dip corresponds to a loop. And in (c) it is shown that a rapid ratio decay, reflecting increasing excitation of System I pigments, is initiated before the I-D dip. These data indicate that the I-D transient is caused by a rapid switch of energy distribution in favor of System I and resulting stimulation of Q reoxidation via the electron transport chain. It is suggested that as with the slow fluorescence transients the rapid also can be understood as a composite of two different changes, (1) direct changes resulting from a switch in energy distribution, which are inverse for F less than 690 and F greater than 715, and (2) indirect changes due to stimulated Q reduction or Q oxidation, which are parallel for both emissions. The rapid ratio decay, correlated to I-D, persists and is even stimulated in the presence of electron transport inhibitors. This and the speed of the phenomenon make it improbable that the rapid energy distribution changes are affected by an ion flux-induced mechanism. It is proposed that the electrical field across the thylakoid membrane is involved in the energy switch mechanism.


Characterization of the oxygen probe pyrenebutyric acid in rabbit heart mitochondria. The fluorescence of pyrenebutyric acid is quenched by oxygen and the quenching is a linear function of the oxygen concentration. In addition, pyrenebutyric acid has been shown to be readily taken up by the cell with a partition coefficient of approx. 200. Results are presented on the effect of pyrenebutyric acid on oxidative metabolism in rabbit heart mitochondria. 1. Pyrenebutyric acid is readily taken up by heart mitochondria: 0.843 +/- 0.087 nmol pyrenebutyric acid taken up by Mr/mg dried weight. 2. Pyrenebutyric acid does not alter the steady-state redox levels (State 1, 2, 4 or 5) of any member of the respiratory chain. 3. Pyrenebutyric acid does not alter the response of cytochrome b, cytochrome c or NADH in the State 4-3-4 transition induced by the addition of ADP. Thus pyrenebutyric acid would appear to be non-toxic to oxidative metabolism.


Inhibition of mitochondrial electron transport by hydrophilic metal chelators. Determination of dehydrogenase topography. The topography of the inner mitochondrial membrane was investigated using inhibitors of electron transport on preparations of beef heart mitochondria and electron transport particles of opposite orientation. Reductions of juglone, ferricyanide, indophenol, coenzyme Q, duroquinone, and cytochrome c by NADH are inhibited to different extents on both sides of the membrane by the impermeant hydrophilic chelators bathophenanthroline sulfonate and orthophenanthroline. The extent of inhibition for each acceptor increased in the order given. At least two chelator-sensitive sites are present on each membrane face between the flavoprotein and coenzyme Q and a chelator-sensitive site is present on the matrix face between the sites of coenzyme Q and duroquinone interaction. Duroquinol oxidation in mitochondria only is stimulated by bathophenanthroline sulfonate. Juglone reduction is stimulated in electron transport particles (only) by p-hydroxymercuribenzenesulfonate, but after mercurial treatment, juglone reduction in both particles and mitochondria is more sensitive to bathophenanthroline sulfonate. Succinate dehydrogenase components are inhibited by hydrophilic orthophenanthroline or bathophenanthroline sulfonate in mitochondria only. Electron flow between the dehydrogenases of succinate and NADH occurs via a chelator-sensitive site located on the matrix face of the membrane. Inter-complex electron flow is prevented by rotenone or thenoyltrifluoroacetone. The lack of succinate-indophenol reductase inhibition by bathophenanthroline sulfonate in the presence of rotenone or thenoyltrifluoroacetone indicates that the rotenone-sensitive site may be located on the matrix face and demonstrates that electrons flow between the NADH and succinate dehydrogenases via a hydrophilic chelator and rotenone-thenoyltrifluoroacetone-sensitive site on the matrix face of the membrane. Inhibiton by hydrophilic chelators only in mitochondria indicates that succinate dehydrogenase as well as NADH dehydrogenase has a transmembranous orientation.


The effect of mono- and divalent cations on the quantum yields for electron transport in chloroplasts. We have previously shown (Gross, E.L. and Hess, S.C. (1973) Arch. Biochem. Biophys 159, 832-836) that low concentrations of monovalent cations (3-10 mM) caused changes in chlorophyll a fluorescence indicative of a transfer of excitation energy from Photosystem II to Photosystem I. These effects were reversed by divalent cations or higher concentrations of monovalent cations. In this study, we have examined the effects of cations on the relative quantum yields for Photosystem II (dichlorophenolindophenol reduction) and Photosystem I (diphenylcarbazone disproportionation) with the following results. (1) Low concentrations of monovalent cations decreased the quantum yield for dichlorophenolindophenol reduction and increased that for diphenylcarbazone disproportionation. These results confirm that cations promote excitation energy transfer to Photosystem I. (2) Higher concentrations of monovalent cations (30-100 mM) had no effect on electron transport. Therefore, the increases in chlorophyll a fluorescence observed at these concentrations may be due to a decrease in the rate constant for radiationless decay. (3) In the absence of Tricine, divalent cations also promote energy transfer from the light harvesting pigments to Photosystem I. However, a direct inhibition of Photosystem I and divalent cations can reverse the Tricine effects.m II photochemistry cannot be rules out. (4) Tricine biases the system in favor of Photosystem I and divalent cations can reverse the Tricine effects.


[Polysensory interaction in the cat posterior ventrolateral thalamic nucleus]. The neurone activity was studied in the posterior ventrolateral nucleus of the thalamus in acute experiments on unanesthetized cats. About 20% of the neurons studied proved to react to the visual and somatosensory stimulation. By the character of reaction to these stimuli the polymodal neurons could be divided into three groups. In elaboration of the active defense reflex to visual electric skin stimulation there were recorded in the mentioned nucleus the rhythm assimilation reaction with the action of the flickering light and its depression in case a biologically significant stimulus was presented against this background. After section of the optic tract and separation of the hemispheres to the cerebellar level the rhythm assimilation reaction and its depression were revealed in the posterior ventro-lateral nucleus of the thalamus at the side of the section of the optic tract. This fact indicated that the leading canal of the entrance of visual afferentation to this nucleus passed through the stem reticular formation.


[Automatic activity of pacemaker cells in the atrioventricular valves of the rabbit heart]. The microelectrode technique applied revealed an automatic activity of the pacemaker cells with slow diastolic depolarization in the cusps of the atrioventricular valves obtained from 34 rabbit hearts. Electrophysiological characteristics of the action potentials of these cells were investigated. Inhibitors of slow sodium-calcium canal (Mn++, Co++, and Mg++ ions) proved to eliminate the automatic activity of the pacemaker cells. When the content of potassium ions was elevated in the perfusion solution, no suppression occurred. It is suggested that the automatic activity of the pacemaker cells in the atrioventricular values depended mainly on the functioning of the slow sodium-calcium canal.


[Effect of angiotensin II on hemodynamics during systemic and portal administration]. The authors studied changes in the general hemodynamics in healthy nonanesthetized dogs in infusion of 27/ng/kg/min of angiotensin II into the superior vena cava and the portal vein. Portal infusion of the peptide produced a less pronounced pressor effect. Elevation of arterial pressure in systemic infusion of angiotension occurred on account of increase in the peripheral vascular resistance with decrease of minute circulation volume. In portal infusion of the preparation elevation of arterial pressure was mainly due to increase of the minute circulation volume. Differences in hemodynamic reactions could not be attributed only to the peptide metabolization in the liver. It is possible that depressor agents entered the blood from the liver in portal angiotensin II infusion.


[Functional state of the spleen in conditions of craniocerebral hypothermia]. Experiments were conducted on dogs. With the fall of body temperature from 36 to 24 degrees C the circulation volume of the spleen decreased from 53.9 +/- 1.94 to 17.9 +/- 0.84 ml/100 g/min, and the arterio-venous difference by oxyhemoglobin - from 19.5 +/- 0.58 to 3.3 +/- 0.23%. Marked body overcooling completely depressed the capacity of the spleen to extract low-resistant erythrocytes from the circulation. A fall of body temperature from 36 to 30 degrees C was accompanied by reduction of the splenic area to 92.6 +/- 2.6%; subsequent chilling led to the accumulation of blood in the pulp with increase of the organ area to 108.7 +/- 4.82%.


[Characteristics of electroencephalographic changes in hypotensive and hypertensive reactions caused by hypothalamic stimulation]. Electrical activity changes of the cortical and subcortical formations in the hypo- and hypertensive vascular reactions induced by hypothalamus electrical stimulation before and after introduction of monoaminohydroxydase inhibitor, vetrasine, were studied in experiments on urethane-anesthetized rabbits. Hypertensive reaction completely blocked by vetrasine were, while hypotensive hypothalamic reactions remained unchanged. These findings are interpreted of the basis of differences in the neurochemical mechanism of the pressor and depressor hypothalamic reactions.


[Effect of high-voltage condenser discharge on the optical properties of from myocardium]. A high voltage condenser discharge provoked a sharp increase in the intensity of a flux of flat-polarized light passing through a strip of the from cardiac muscle. This could point to changes in the optic properties of the tissue caused by conformative changes of the membrane proteins.


[Incorporation of thymidine-H3 into the DNP of rat tissues following a single injection of DNA]. The injection of a homologous DNA to rats caused an increased incorporation of H3-thymidine into DNP of the bone marrow, the spleen, the thymus, and the intestinal mucosa 24 hours after the administration. This effect was not revealed on the 3d day.


[Characteristics of skeletal muscle tissue ribosomes]. Electron-microscopic and chemical analysis of the fraction of RNP-particles, samples of the muscle tissue of the posterior limb of rat and of the human musculus rectus abdominis was carried out for the purpose of characterizing ribosomes of the skeletomuscular tissue. RNP-particle fraction proved to contain functionally-active mono- and poly ribosomes. Two RNA fractions-- RNA1 and RAN11 were isolated. RNA1 proved to represent a set of ribosomic RNA with sedimentation coefficients 26-28S, 16-18S and 4-5S. RNA11 contained no ribosomal RNA, and by its nucleotide composition was affiliated to the nucleotide compostion of rat DNA. The structural organization of ribosomes in the cytoplasm of the muscular fibers corresponded to the pictures observed in the RNP-particle fraction. Polyribosomes are determined in the regions of physiological regeneration of myofibrillae and represent complexes consisting of 5 and more monoribosomes arranged in the form of beads. Ribosomes-like particles proved to escape through the nuclear menbrane; this fact, along with the data of chemical analysis pointed to the periodic passage of RNA from the nucleus into the cytoplasm of hte muscle fiber.


[Effect of succinic semialdehyde on nitrogen metabolism of animal brain tissue during hypoxia]. In examining the content of free ammonia, glutamine and some free amino acid s in the brain tissue of mice under normal conditions, in hypoxia and under the effect of succinic acidsemialdehyde, in hypoxia there was revealed a marked increase in comparison with the normal conditions) of the content of free ammonia, and alpha-alanine, a reduction of glutamine; there was also a slight elevation in the content of gamma aminobutyric acid and no changes in glutamic and asparagic acid content. In case of pretreatment with succinic acid semialdehyde the content of free ammonia, glutamine and alpha-alanine in hypoxia approached the normal value. One of the possible mechanisms of the antihypoxic effect of succinic acid semialdehyde was transformation of this compound as a results of which there occurred synthesis of glutamic acid and glutamine leading to detoxication of free ammonia accumulating in the brain tissue in hypoxia.


[Effect of carbon tetrachloride on RNA metabolism in rat liver]. The effect of chronic CCl4 treatment on both the liver RNA content and 3H-uridine incorporation was studied. Comparison of morphologic and biochemical parameters allowed to define two successive stages of toxic process resulting in septal fibrosis. The most significant changes in the rat liver rapid RNA turnover were observed during the first 3 months of the toxic agent action. The metabolic disturbances were also manifest in both decreased RNA content and changes of nuclear-cytoplasmic interrelationships in the damage liver tissue.


[Relation between oxidation and phosphorylation in gastric mucosa mitochondria]. The authors studied the state of cell respiration and oxidative phosphorylation in the mitochondria of the gastric mucosa at various phases of its function. Stimulation of secretion with histamine led to a distinct increase in the rate of mitochondrial respiration in the gastric mucosa against the background of a marked fall of the conjugation coefficient level, including P/O. The mentioned changes in the energy conjugation of mitochondria of the parietal cells preceeded activation of HCl secretion.


[Effect of psychostimulants on the relearning by rats of the avoidance direction in a U-shaped labyrinth]. The capacity of rats to relearning the direction of the avoidance in a U-shaped maxe was determined. Four traning sessions--each time in a new direction (to the right, or to the left) of running were conducted. D, 1-amphetamine given in low and medium doses (0.5 and 2 mg/kg) shortened the latent response periods and failed to influence the relearning of the animals. A high dose of the drug (5 mg/kg) led to reduction of the latency of the responses, but at the same time inhibited the reconstruction of the avoidance habit; this distinctly correlated with the intensification of space preference. Caffine (25 and 50 mg/kg) failed to influence the relearning of rats.


[Choleragen and neuraminidase production by Vibrio in vitro]. In vitro studies demonstrated a high degree of the rank correlation between the synthesis of cholera exotoxin and neuraminidase by cholera vibrios (V. cholerae 569B). The appearance of these biochemically-active materials proved to depend on the growth phase of the microbial population. A possibility of cooperation between them in the pathogenesis of cholera is suggested.


[Effect of ethirazol and parmidine ofn the development of experimental atherosclerosis in rabbits]. Experiments on rabbits which received cholesterol in food for 3-4 months showed an inhibitory effect of ethirazol (bis-methylamide-1-ethyl-pyrazol-3,4-bicarbonic acid) and parmidine (piridinolcarbamate, 2,6-bis-hydroxymethylpiridine bis-n-methylcarbamate) on the development of experimental atherosclerosis: there proved to be a reduction of accumulation of total cholesterol in the aorta and of its atherosclerotic affection. At the same time the blood serum cholesterol, triglycerids and phospholipid content was not significantly changed by these drugs.


[Model of a chronic Vibrio cholerae carrier based on gnotobiotic rats]. Germ-free monoflora (contaminated with nonpathogenic spore-bearing bacillus) and common albino rats (OFA) were infected with V. cholera El Tor, of Ogava and Inaba serological types (6 milliard microbial cells per 1.5 ml of physiological solution per rat). Approximately one week after the infection the number of vibrios reached hundreds of millions per 1 g of feces and persisted at this level for over 100 days (observation period). Newborn rats were infected by natural way from adult vibrio carriers and also became vibrio-carriers. The number of vibrios excretedby the animals which were germ-free and monoflora before the infection was approximately the same. Cholera vibrios perished completely in the enteric tract and were never revealed in the feces of common (control) rats.


[Study of the virustatic action of rimantadine based on a phage-bacterium model]. The action of rimantadin on the lambda phages was studied. The maximal inhibitory effect on the compound was observed on the 1st-6th minutes after the infection. There was no such effect on the T-4 and lambda phage replication. According to the data of incorporation of the radioactive precursors into the phage DNA,  RNA,  and proteins, and the manifestation of the rimantadin action on phage replication it was supposed that the inhibitory effect of rimantadin was determined by its influence on the RNA-polymerases, preponderantly on the phage RNA-polymerase.


[Role of leukocyte disintegration products in increasing macrophage resistance to the causative agent of orinthosis]. The dymanics of formation of macrophagal granulomas in the liver of albino mice was studied after intravenous infection with the causative agent of ornithosis. In formation of granulomas macrophages underwent the stage of reutilization of the leukocyte disintergration and became resistant to the causative agent of ornithosis. Together with the leukocyte remants histones and cation proteins could penetrate into the macrophages cytoplasm; these displayed a high antironithosis activity in vitro. An increase of macrophage resistance to the causative agent after reutilization of the products of leukocyte disintegration apparently sreved as one of the mechanisms of resistance formation in the foci of inflammation in ornithosis.


[Effect of sarcolysin and asalin on the incorporation of thymidine-H3 in the DNA of sarcoma 45 and tissues of tumor-bearing rats]. A comparison was made of the action of sarcolysin and asalin on the synthesis of DNA in sarcoma 45, the spleen, thymus, bone marrow and liver of tumour-bearing rats depending of the time of administration of the preparation. There was seen a direct relationship between the selectivity of sarcolysin and asalin action with a different bearer structure and the capacity of these perparations to depress DNA synthesis in the tumour and in normal tissues.


[Diurnal periodicity of mitotic activity, DNA synthesis and duration of mitosis in mouse bone marrow cells]. A clear diurnal rythm of the mitotic activity and DNA synthesis was observed in the cells of myeloid and erythroid series of mouse bone marrow, maximum number of mitoses and DNA-synthesising cells coincided in time and occurred during day and night hours minimum--during morning and evening hours. A rise in the mititic activity was due to the increase in the number of dividing cells but not to the increase in duration of mitosis.


[Effect of encephalectomy on the corticosterone content of rat fetal adrenals]. Changes in the functional state of the hypophysial-adrenal system after the removal of the hypothalamus (encephalectomy in utero) were studied in rat fetuses. The hormonal activity of the adrenal glands was evaluated by the direct fluorimetric determination of corticosterone in this organ. Removal of the hypothalamus in 18.5--19.5-day fetuses brought about a significant decrease of corticosterone in the adrenal glands. Injection of the hypothalamus homogenate to fetuses immediately after the encephalectomy prevented this decrease. The results obtained supported the existence of functional relationship between the hypothalamus and the hypophysial-adrenal system in rat fetuses.


[Functional morphology of the vascular portion of the pancreas transport system]. The vascular part of the pancreas transport system is represented by capillary bed, pericapillary space and intercellular clefts. On the surface of the acinar cells and of the fibroblasts there are cytoplasmic plates facing the pericapillary space and the intercellular clefts. The vascular part of the pancreas transport system provides delivery of the products to the acinar cells, transport of the hormones, destructed cell structures and partly of digestive enzymes to the capillaries of the pancreas.


[Damage to and regeneration of the kidney epithelium following crushing of the soft tissues of the extremities]. Dynamics of the cellular composition in the proximal thin, thick areas of the loop, distal portions and collective tubules of the kidney was studied in rabbits after crush of the soft tissues of the limb. Planimetric method was applied to determination of the area of the nuclear epithelium of the proximal, distal portions and the collective tubules. A relationship was revealed between the injury of the epithelium of the nephrons and the collective tubules and its restoration, and also an intensification of mitotic activity, elevation of the relative number of pathological mitoses, and increase of the mean size of the cell nuclei.


[Application of scanning electron microscopy to studying the architectonics of the fibrous framework of the walls of large vessels]. Scanning electron microscopy was used to study the architectonics of the connective tissue fiber framework in the walls of large arteries. Preliminary treatment of the vascular samples with proteolytic enzymes (protorysin, trypsin) offered a possibility of determining peculiarities attending distribution and interrelations of collagen and elastic fibers in different strata of the vascular wall.


[Cytological organization of the hepatic ligament in rats]. A method of integration frequencies of distribution of classes of hepatocytes, DNA-synthesising cells and mitoses along the hepatic balk was applied to the study of the cytological organization of the balk in rats of different age. Distribution of subpopulations of hepatocytes in the hepatic balk displayed distinct features of space organization: most of mitoses and of the DNA-synthesizing hepatocytes were localized at the beginning of the balk, the first nuclear class prevailed at the beginning and the end of the balk, and the second class--in the middle of the balk. The results presented served as an additional confirmation of the presence of self-renewal processes in the liver of adult rats.


[Enterochromaffin cells of the rat duodenal mucosa]. Enterochromaffine cells (ECC) of the rat duodenal mucosa were revealed by Falk-Hillarp's fluorescent-histochemical method, by Masson-Hamperl's method and by diazoreaction with fast red. ECC were arranged among the cells of the surface epithelium of the crypts and villi. These cells were of bottle shape in the villi and of triangular form--in the crypts. The number of ECC found by the mentioned methods in the crypts and the villi varied: by Falk-Hillarp's method--210.4 +/- 0.02, by Masson-Hamperl's method--182.5 +/- 0.05, and by the diazomethod--73.7 +/- 0.02.


[Effect of the periodic action of potassium bichromate of the state of the renal parenchyma and lethality of white mice]. A study was made of the state of the tubular apparatus in 360 albino mice given repeated subcutaneous injections of potassium bichromate with intervals of 1 day, 1 week and 1 month. A more frequent action of the pathogenic agent proved to lead to a lesser lethality of the animals and produce a lesser toxic effect on the renal tubulers.


[Cytochemical characteristics of hematopoietic elements in laboratory animals]. Distribution of alkaline and acid phosphatases, L-naph-thylacetateesterase, peroxidase, lipids and glycogen was studied in the blood cells and bone marrow of mongrel albino rats and guinea-pigs by means of cytochemical methods. The intensity of reactions was assessed by Karlow's method. Cytoenzymatic characteristics of the hemopoietic elements and the character of changes in their metabolism during cell differentiation and maturation were ascertained. Quantitative species differences in the content of chemical substances in the blood and bone marrow cells of rats and guinea-pigs were revealed.


[Cell precursors of fibroblasts detected by cloning in vitro hematopoietic organ crlls of normal and irradiated mice]. Fibroblast colonies (clones) are formed in monolayer cultures of the bone marrow, spleen and thymus cells from adult mice, the colony-forming efficiency (per 105 cells) was 2.2, 0.2 and 0.16, respectively. About 50% of the bone marrow CFU-F were destroyed immediately after the total body irradiation with 150r; the following 6 days the number of CFU-F decreased to 10% of the normal value. The normal level of the CUF-F concentration was reached in the bone marrow on the 25th postirradiation day.


[Lymph node and spleen morphology in gnotobiotic rats]. The lymph nodes, the spleen and the adrenal cortex were studied in 12 gnotobiotic and 12 control Wistar rats by routine histological and histochemical methods. It was shown that the absence of normal microbial flora suppressed the development of zone B of the lymphocytes in the lymph nodes; it was accompanied by an increase in the thickness of the adrenal cortex and of the lipid inclusions in its cells, but had no influence on the lymph follicles of the spleen. A conclusion was drawn that inhibition of lymphopoiesis in the lymph nodes occurred as a result of absence of a direct microbial stimulation and was mediated via the hormonal factors; this failed to influence the lymphopoiesis of the spleen maintained by stimulation within the organ itself.


[Effect of quercitrin on structural changes in the large and small intestines in experimental enterocolitis]. Sensitization of rats with the homologous antigen of the large intestine with Freund's stimulant caused marked immunomorphological shift in the large intestine of rats with the phenomena of enteritis in the small intestine. Oral administration of quercitrin in doses of 25 and 100mg/kg for 10 days promoted decline of focal lymphohistiomonocytic infiltrations, of eosinophilic in the mucosa and of scleroti changes in the large intestine. At the same time restoration of structural disturbances occurred in the small intestine. The influence of quercitrin on the morphological changes in the epithelium of the large and small intestine mucosa were insignificant. It is believed that the therapeutic action of quercitrin could be caused by restoration of local circulation deranged in animal sensitization.


[Ultrastructure of the duodenal mucosa in rats under stress]. Electron microscopy study of the duodenal mucosa of rats after a 24-hour restrain stress was conducted in a special apparatus. Moderate changes of enterocytes chiefly consisting of focal destruction of mitochondrial cristae and increase in the number of lysosomes were revealed. These results correlate with the previously published data on histochemical study of the same objects. The changes of the  goblet cells and of the blood vessels are described.


[Changes in the morphology of jejunal mucosa in conditions of bilateral subdiaphramatic vagotomy]. Bilateral subdiaphragmatic vagotomy led in rats to the development of a complex of structural and ultrastructural changes in the jejunum mucosa and of principal cell forms of its epithrlium--enterocytes and goblet cells. At early periods after the operation (1.7 of a day) morphological changes of a destructive character prevailed, while at late periods (60, 120 days) compensatory reconstructions were mainly observed.


[Cultivation of human peripheral blood leukocytes on agar gel]. It was shown by the modified method of agar cultures that in the peripheral blood of a healthy man, aged from 4 days to 40 years. The number of cell precursors of granulocytes and macrophages (CFU-C) varied from 0.05 to 6.38 in adults and from 0.2 to 2.9 in children per 105 nuclear cells. CFU-C content in the patients with infectious mononucleosis and acute leukemia was 0.5--14 and 0--0.3 per 105 nuclear cells, respectively.


Evaluation of the role of in vivo proteolysis (fibrinogenolysis) in prolonging the thrombin time of human umbilical cord fibrinogen. These studies have been directed at evaluating the role played by proteolysis (fibrinogenolysis) in vivo in prolonging the thrombin time of human umbilical cord ("fetal") fibrinogen. The aggregation rate of cord fibrin compared with that from adult plasma is always delayed when the reaction is carried out under conditions of relatively high ionic strength (e.g., 0.29); this difference is not apparent at relatively low ionic strength (e.g., 0.09). In addition, as assessed by turbidimetric techniques, the maximum absorbance attained by cord fibrin is considerably less than that attained by adult fibrin. Coagulable fibrinogen catabolites (i.e., fraction I-5) are present in cord plasma and, like their counterparts from adult plasma, lack various portions of the COOH-terminal region of the A alpha chain. However, their presence in plasma does not explain the behavioral differences between cord and adult fibrin. Moreover, differences revealed by turbidimetric comparison of cord and adult fibrin from plasma fraction I-2 persist in fibrin from fraction I-5; it therefore appears that the COOH-terminal region of the A alpha chain does not contain the structure(s) accounting for the unique behavior of "fetal" fibrinogen.


Effect of heterologous antibody on human platelets. The effect of heterologous anti-human platelet antibody on human platelet function was examined in the presence and absence of whole plasma as an in vitro model for antibody-induced immune damage to cells. Heterologous IgG anti-human platelet antibody mediated platelet aggregation and released serotonin from both platelets in plasma and from platelets isolated by gel filtration and increased the availability of platelet acid phosphatase in a dose-response fashion. Anti-platelet antibody failed to release beta-glucuronidase (lysosomal enzyme marker) or cause lactic dehydrogenase loss (cytolysis). The effect of the antiplatelet antibody on platelets proceeded in the absence of complement. The active molecule in the anti-platelet antiserum was isolated in the IgG fraction and all three indicators of platelet injury were mediated by purified monomeric IgG. Thrombin was not required for the antibody-mediated effects, as three thrombin inhibitors failed to block the reaction. EDTA was an effective inhibitor, suggesting a cation requirement; however, as little as 38 muM calcium was sufficient for effective platelet aggregation and release. The inability of acetylsalicylic acid to inhibit the effect of the antiplatelet antibody suggests that heterologous antibody (IgG) induced platelet alteration proceeds by a different mechanism than that mediated by ADP and epinephrine and does not involve endogenous platelet prostaglandin synthesis.


Separation of megakaryocytes from mouse bone marrow by density gradient centrifugation. The density profile of mouse bone marrow megakaryocytes, as determined by discontinuous albumin density gradient centrifugation, was characterized by a single density population (1.088 to 1.119 g/ml) with a peak density of 1.10 g/ml and a maximum enrichment of 15.5. This single population comprised both mature and immature megakaryocytes. The density profile of small, acetylcholinesterase-positive cells, a class of potential megakaryocyte precursors, was almost identical to that of morphologically recognizable megakaryocytes.


Identification of monocytes in suspensions of mononuclear cells. A new histochemical technique for morphological studies of mononuclear cells and granulocytes, based on fluorescent staining with methyl green, pyronine Y, and stilbene-isothiocyanato disulfonic acid (MPS stain) is described. The method was applied to mononuclear cells isolated from the blood of normal human subjects by Ficoll-Isopaque density centrifugation. Three cell populations were distinguished, mainly on the basis of differences in morphology and cytochemistry, utilizing the MPS stain. One of the cell types had many of the morphological characteristics of the monocyte. This technique, augmented by lysosomal content and endocytosis capacity studies, revealed contimination of the cell suspension with a larger percentage of monocytes than has usually been reported in the literature.


Degranulation and abnormal bactericidal function of granulocytes procured by reversible adhesion to nylon wool. Granylocyte bactericidal capacity, chemotaxis, hexose monophosphate shung activity (before and after phagocytic stimulus), and quantitative nitroblue tetrazolium reduction and enzyme content were examined in cells obtained by filtration leukaphresis (FL) and continuous-flow centrifugation (CFC). A decrease in the bactericidal efficiency of FL-produced cells compared to that of both normal and CFC-procured granulocytes was found; the decrease was 17% with a cell-to-bacteria ratio of 5:1, and 55% with a 1:1 ratio. Moreover, FL-acquired cells were often vacuolated and consistently contained less acid phosphatase and beta-glucuronidase than did normal granulocytes. When normal cells were incubated for 1-2 hr with nylon wool, 30% of the total acid phosphatase and beta-glucuronidase was released, with no evidence of cell death, thus suggesting degranulation. Similar results were obtained with glass, cotton, or polysulfone plastic fibers. Electron microscopic and peroxidase cytochemical studies of the adherence of normal granulocytes to nylon fibers were also carried out. After 30 min of incubation, cell-to-fiber attachment and cellular aggregation had occurred, although the cells per se appeared normal. After 60 and 120 min, other changes became apparent: (1) a decrease in the amount of cytoplasmic granules; (2) large, intracytoplasmic vaculoles; and (3) extracellular peroxidase on fiber surfaces. We conclude that granulocytes obtained by adherence to nylon fibers show both morphological and biochemical evidence of degranulation and diminished bactericidal capacity, and that these abnormalities may be causally related to decreased granulocyte survival in transfusion recipients.


Familial deficiency of glutathione reductase in human blood cells. A virtually complete absence of glutathione reductase activity was found in the erythrocytes of all three children (one male, two females) from a consanguineous marriage. Intermediate values were found in the erythrocytes of both parents. The enzyme activity could not be restored either by addition of FAD in vitro or by administration of riboflavin in vivo. The amount of reduced glutathione in the erythrocytes was normal in each case. Severely diminished glutathione stability during incubation with acetylphenylhydrazine was observed in the erythrocytes of the siblings, as well as intermediate stability in the parents' red cells. Clinically, this deficiency was manifested by hemolytic crises after eating fava beans in the eldest daughter (patient), and possibly by cataracts in her own and in her brother's eyes. Very low activities of glutathione reductase were also found in the leukocytes of this family: 13%-15% of normal values for the children and 64%-66% for the parents. Moreover, the same deficiency was found in the purified white blood cells of the propositus: 8% of normal values in the polymorphonuclear (PMN) cells, 4% in the lymphocytes, and 15% in the monocytes, together with 11% in the platelets. Finally, we found an abnormal oxygen consumption of the propositus' PMNs after phagocytosis of zymosan particles, suggesting that the glutathione reductase reaction was involved in the bactericidal capacity of these cells.


Role of copper in mitochondrial iron metabolism. Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.


Evidence that functional subunits of antihemophilic factor (Factor VIII) are linked by noncovalent bonds. Partially purified human antihemophilic factor (AHF, factor VIII), when treated with high concentrations of salt, has been shown to dissociate into two components: one, of relatively low molecular weight, possesses procoagulant activity, and the other, of higher molecular weight, forms precipitates with heterologous antiserum against AHF and supports ristocetin-induced platelet aggregation. The ease of separation suggests that the two components in the native state might be held together by noncovalent bonds. Earlier observations do not exclude the possibility that the subunits may be covalently bonded in nature but might be severed by plasma proteolytic enzymes during laboratory manipulation. The issue was examined by preparing partially purified AHF from fresh human plasma in the presence of protease inhibitors, including benzamidine, soybean trypsin inhibitor, epsilon-aminocaproic acid, heparin, and hirudin. Under these conditons, gel filtration in the presence of 0.25 M calcium chloride and 0.001 M benzamidine resulted in its separation into two components, having properties identical to those separated in the absence of these protease inhibitors. The inhibitor mixture blocked generation and action of streptokinase- and kaolin-activated plasmin from plasma, and protected both plasma AHF and partially purified AHF from the action of thrombin. Surface-induced activation of PTA (factor XI) was partially inhibited, and that of Christmas factor (factor IX) was completely inhibited. This observation provides further evidence that in the native state the high- and low-molecular-weight components of preparations of antihemophilic factor are held together by noncovalent bonds.


Immunosuppressive therapy of Factor VIII inhibitors. Immunosuppressive therapy was used in seven hemophiliac and three nonhemophiliac patients with factor VIII inhibiors. Permanent disappearance of the inhibitor occurred in three hemophiliac and two nonhemophiliac patients following treatment with cyclophosphamide and factor VIII. Critical factors influencing the response to therapy may include both the titer and duration of the inhibitor and the degree of intervening factor VIII exposure prior to immunosuppressive therapy. Two severe hemophiliacs with low titer inhibitors that disappeared without specific therapy are also reported.


Modification by temperature of the response of isolated aorta to stimulatory agents and transmural stimulation. Contractile responses of helically-cut strips of the rabbit aorta to drugs, ions and transmural electrical stimulation were compared at different temperatures of the bathing medium, the response at 37 degrees C being taken as control. The dose-response curve of norepinephrine was moved to the right and downward by lowering the temperature from 37 to 25 degrees C and by raising temperature to 40 degrees C. Responses to transmural neural stimulation at frequencies of 5 and 20/sec were attenuated at 25 degrees C, the attenuation being greater in the response at the lower frequency. Concentrations of exogenous norepinephrine needed to produce the same magnitude of contraction as that with transmural stimulation were markedly increased by lowering the temperature to 25 degrees C. Contractile responses to norepinephrine (2 X 10(-6) M), histamine (2 X 10(-5) M) and angiotensin II (10(-7) M) were attenuated by 32-44% at 25 degrees C, whereas the responses to K+ (25 mM) and Ba++ (2 mM) were dependent on temperatures between 25 and 37 degrees C and were attenuated by 69 and 92%, respectively, at 25 degrees C. Contractures induced by Ca++ in K+-depolarized preparations exposed to Ca++-free media and also by Ba++ in preparations exposed to Ca++-free media varied directly by raising temperatures. Interference with the influx of divalent cations, such as Ca++ and Ba++, may be involved in the cold inhibition of aortic contractility.


Skeletal muscle vascular volume changes with increased venous pressure. Dog gracilis muscles were removed, enclosed in a plethysmograph and perfused at constant inflow pressure or constant inflow. Circulating blood volumes were measured by the constant infusion technique using RBC-51Cr or albumin-131I. Control venous pressure averaged 3 mm Hg and elevations (delta PV) over the range of 5-40 mm Hg were produced. Volume changes were determined during and following delta PV by plethysmography and by changes in total muscle radioactivity. Changes in total (amount of blood in the tissue), active (circulating), and mobilized vascular volumes were calculated. Active vascular volumes and total vascular volumes increased with venous pressure increments up to 25 mm Hg and then plateaued. Active vascular volumes (indicators) increased by amounts significantly greater than the increases in total vascular volume (plethysmography). Volume changes in the constant flow groups were double those in the constant pressure groups. The mobilized active vascular volume (active vascular volume change minus total vascular volume change) consists of a volume of blood contained in vessels unattainable by the indicators during the control period but which were made available to the indicator by the delta PV. Mobilized vascular volume averaged 45% of the active vascular volume change. With venous pressure elevation there was an increase in the RBC-51Cr volume to albumin-131I volume ratio. This suggests a redistribution of red cells with respect to plasma, possibly resulting from reduced plasma skimming.


Responsiveness of isolated dog veins to bradykinin and other bioactive peptides: distribution of sensitivity to bradykinin and possible correlation with genesis of the venous system. Contractile responses of isolated dog veins to bradykinin were studied. Responses to norepinephrine were taken as standards. According to their sensitivity to bradykinin, the veins obtained from 14 sites of the venous system were divided into two groups, while all the veins were almost uniform in their sensitivity to norepinephrine. One group has high sensitivity to bradykinin and the other has low sensitivity. The former includes the pulmonary, hepatic, splenic, and portal veins, the anterior vena cava, and the upper and the middle divisions of the posterior vena cava. The latter includes the external jugular, cephalic, azygos, femoral, and saphenous veins, and the lower division of the posterior vena cava. The responses of the renal vein were intermediate. A striking correlation was noted between the distribution of bradykinin sensitivity and the genesis of the venous system. Five bioactive peptides other than bradykinin were also studied. Only angiotensin induced contraction in some preparation, but, as a whole, caerulein, eledoisin-related peptide, oxytocin and vasopressin rarely showed contractile activity.


Space phobia: syndrome or agoraphobic variant? Four elderly women had intense fears of falling when there was no visible support at hand or on seeing space cues while driving. Two patients had cervical spondylosis. The mean age at onset of the fear was 54--thirty years later than that for agoraphobia. Fear of public places and of heights was not prominent, nor was depersonalisation or depression. These "space phobias" might be a hitherto unrecognised syndrome or an unusual variant of agoraphobia. The visuospatial reflexes involved might illuminate the pathogenesis of certain fears.


Detection of renal anomalies by abdominal palpation in newborn infants. In a new technique of palpation for renal anomalies in the newborn one hand supports the infant while the fingers of the other hand support the loin and the thumb explores the abdomen. In a series of 11 000 otherwise normal newborn children superficial palpation detected 11 renal anomalies, and deep palpation led to the discovery of another 42 anomalies. One of two other series in which palpation was performed bimanually gave a similar incidence of renal anomalies (0-5%). Early discovery of an asymptomatic anomaly enables early treatment of the complications that are often found in patients with congenital renal anomalies detected in later life.


Sensitisation to Hodgkin's disease spleen tissue in patients with malignant lymphoma: follow-up study. The leucocyte migration responses of patients with malignant lymphoma to an unidentified factor in Hodgkin's spleen tissue were serially studied and related to clinical progress. Initial sensitisation responses did not correlate with presenting histological or clinical status or with subsequent clinical progress. Enhancement of responses after treatment, however, was associated with good clinical progress. In patients who relapsed, sensitisation to spleen factor diminished, whereas responses were preserved at one year in those in maintained remission. Sensitisation to the splenic factor may be a useful index of response to treatment in patients with malignant lymphoma; diminishing sensitisation may indicate relapse.


Closed mitral valvotomy.

Closed mitral valvotomy. The results of closed mitral valvotomy operations in 359 patients operated on from August 1957 to October 1974 were assessed at July 1975. About 60% of the patients were in good health. These results suggest that there is still a place for closed mitral valvotomy in carefully selected cases.


The Isis Centre: a counselling service within the National Health Service. A new centre has been established to provide readily accessible counselling, consultation, and mental health information. People may refer themselves or are recommended to attend by general practitioners or other agencies. The counsellors have varied backgrounds in paramedical or counselling services, and they are supported by psychiatrists. Of a sample of 100 clients, four were referred to one of the team's psychiatrists and 33 visited the centre only once. The centre's staff aim to adopt a flexible approach to the client and his problems, and formal psychiatric categories have not been found useful. Provision is made for people who want to solve their problems by discussion rather than medication and those for whom the existing psychiatric services may have little time to spare. Consequently, the approach adopted by the Isis Centre, whereby many people benefit from psychotherapy yet the psychiatrist deals directly with only a few selected cases, contributes towards meeting the great need for psychiatric services and using the psychiatrist's skills more effectively.


Treatment of diabetic coma with small intravenous insulin boluses. The clinical efficacy of small intravenous boluses of insulin in treating diabetic decompensation was tested in 23 patients presenting in either a ketoacidotic or a nonketotic diabetic coma. In addition to the usual ionic and fluid replacement, the patients received hourly intravenous injections of insulin 5 IU. This dose lowered blood glucose levels in all but two patients. In the patients who responded the percentage decrease in glycaemia was similar whatever the initial glucose concentration and averaged (+/-SE of mean) 50+/-3% in five hours. Close monitoring of insulin and glucose concentrations after intravenous insulin in three patients showed that despite the short half life of insulin the effect of the intravenous bolus lasted for about 60 minutes. The overall clinical effectiveness of this type of treatment is comparable to that of the other low-dose regimens. Owing to its simplicity, this technique of insulin administration seems most suitable for the routine treatment of diabetic coma.


Acute responsiveness to calcitonin in chronic renal failure. The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.


Significance of low body weight in ovulatory dysfunction after stopping oral contraceptives. In a group of patients who developed ovulatory dysfunction on stopping oral contraception the mean body weight of those with previosly regular cycles was significantly lower than that of women who had had ovulatory dysfunction beforeoral contraception and also that of a control group. Women of low body weight may be at particular risk of developing post-pill amenorrhoea even when there is no history pointing to ovulatory dysfunction. This should be considered when selecting a form of contraception in such women.


Ambulance ride: fixed or floating stretcher? The alternatives of a purpose-bult ambulance and a specially designed stretcher suspension system were considered and the features of the latter assessed by subjective and objective tests. The results showed a significant improvement in the quality of the ride offered to the patient.


Child health clincs and inverse care laws: evidence from longitudinal study of 1878 pre-school children. In a longitudinal study it was intended that 1878 children should receive periodic developmental examinations from the age of 6 weeks to 3 years. The children were divided into those with a high or low  risk of developmental problems. Although clinic attendance rate of 85-89% were achieved in the catchment area 100% coverage was difficult because of population mobility and non-attendance at clinics. Children in families who moved away from the area were more difficult to trace and thus more likely to miss developmental examinations. This was a greater problem in the high-risk group. Altogether 683 home developmental examinations were carried out on 269 children who did not attend clinics. Thirty-five per cent of these children were in the high-risk group compared with 22% in the study population, and significantly more had developmental problems. Thus one possible way of reaching and helping such children is though home developmental examinations.


Surface specializations of neurites in embryonic mouse spinal cord. Focal surface specializations occur upon axons, axon growth cone filopodia and, somewhat less frequently, upon dendrites as well as dendritic growth cones in embryonic mouse spinal cord. These surface specializations are observed during the early synaptogenic period (embryonic days 12-16) when the axons of the marginal zone are forming synaptic junctions with motor neuron dendrites growing into their domain. At relatively low electron microscopic magnifications, the specializations appear as discrete patches of electron-dense material located just outside the plasma membrane. Higher resolution and an optimum section plane reveal the following ultrastructural characteristics of these specializations. There is a narrow (approximately 5 nm) less dense layer between the outer surface of the plasms membrane and the thicker (approximately 11.5-15 nm) electron-dense, distal layer of the specializations. The dense layer contains spherical profiles (approximately 10-15 nm in diameter) which have relatively clear centers and non-laminar, opaque perimeters. The surface specializations are commonly associated with an accumulation of dense, fibrillar cytoplasmic material that undercoats the cytoplasmic surface of the plasma membrance directly opposite to the external specializations. Furthermore, some of these surface specializations appear to be forming or merging with the cleft material of protosynaptic junctions and primitive puncta adhaerentia-like contacts. We have also examined the pattern of concanavalin A-peroxidase staining on the cell surfaces in embryonic spinal cord. At embryonic day 13, the earliest stage examined in the concanavalin A-peroxidase experiments, there is already an ubiquitous staining around all the cellular processes in the marginal zone as well as around the perikarya and processes of cells located in the intermediate and ventricular zones. No selective enhancement of neurite surfaces occurred which might have correlated with the surface specializations described above. Finally, the possibility is discussed that the neurite surface specializations might play some role in intercellular recognition phenomena leading to the formation of synaptic junctions and puncta adhaerentia.


Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice. Subregions of the rat hippocampal slice were investigated in relation to (a) the presence of long-term potentiation and (b) responsiveness to low-frequency stimulation. Long-term potentiation was observed in CA1, CA3 and dentate. The effect occasionally lasted up to 6 h, developed gradually, and depended upon repeated low-frequency tetani for maximal effect. To low-frequency monosynaptic stimulation, areas CA3 and CA1 exhibit response facilitation whereas the dentate gyrus exhibits response depression. Reponsiveness in all areas was influenced by stimulus frequency. Recovery was rapid in all areas.


Stimulation of the gerbil's gustatory receptors by disaccharides. The gustatory responses from the chorda tympani nerve of the Mongolian gerbil, Meriones unguiculatus, were treated with 13 disaccharides. Sucrose was the most stimulatory sugar. The ability of fructosyl glycosides to stimulate may depend upon the linkage between fructose and the glycoside. Disaccharides possessing 1 leads to 3, 1 leads to 4, or 1 leads to 6 linkages were poor stimuli compared to sucrose which has a 1 leads to 2 linkage. Glucopyranosyl disaccharides with an alpha-linkage were better stimuli than the beta-anomers, while galactopyranosyl disaccharides possessing a beta-linkage were better than their alpha-amoners.


Stimulation of the gerbil's gustatory receptors by monosaccharides. The gustatory responses of the Mongolian gerbil were tested with a large number of monosaccharides. Electrophysiological methods were used to record from the chorda tympani nerve. Methyl glycosides which have structural features in common with sucrose are the most effective monosaccharides for eliciting a neural response. Among the monosaccharides tested, efficacy appears to be highest in D-pyranosides having equatorial substituents at the C-2 and C-4 positions and axial substituents at the C-1 position. A C-5 hydroxymethyl group is not required. Similarities in the structural requirements for taste response in the fly and gerbil are discussed.


Stimulation of the gerbil's gustatory receptors by polyols. The gustatory responses of the Mongolian gerbil were tested with 12 sugar alcohols. The electrophysiological effectiveness of the linear polyols as gustatory stimulants increased as the length of the carbon chain increased from 2 to 5. Six and 7 carbon acyclic polyols were no more effective than the pentitols. By comparison myoinositol, a cyclic polyol, was more effective in evoking a response. Responses to mixtures of D-sorbitol and sucrose suggest that these sugars compete for a common receptor site. A sucrose receptor site and a model of it is proposed.


The effect of two anesthetic agents on norepinephrine and dopamine in discrete brain nuclei, fiber tracts, and terminal regions of the rat. Catecholaminergic neurons have been implicated in the mechanism of general anesthesia, but previous attempts at measuring changes in adrenergic neuron function during anesthesia have been limited by techniques to whole brain. Microdissection techniques and sensitive radioisotopic-enzymatic assays were used to measure levels of catecholamines in 20 different nuclei, fiber tracts or nerve terminal regions in brains of rats anesthetized for 90-105 min with 1% halothane or 18% cyclopropane. These two anesthetics were chosen because of their diverse effects on the electroencephalogram and on the cardiovascular and respiratory systems. Of the areas examined, significant increases in norepinephrine content with both anesthetic agents were found only in the nucleus accumbens, locus coeruleus and central gray catecholamine areas. Only in the nucleus accumbens was the dopamine level increased by both anesthetics; cyclopropane, but not halothane anesthesia, also increased the dopamine content of the caudate nucleus, while halothane, but not cyclopropane anesthesia, significantly decreased the dopamine level of the ventral nucleus of the thalamus. Changes in levels of transmitters do not distinguish cause from effect of anesthesia, and further experiments are needed to delineate what role, if any, the specific areas play in muscle relaxation, analgesia, sleep or anesthesia. This study shows that a drug can affect one nucleus or region without significantly affecting other regions that contain the same transmitter substance, and that changes in transmitter levels can occur selectively in different regions of brain even if the nerve endings are derived from contiguous cell bodies.


Biochemical changes in unilateral brain injury in the rat: A possible role of free fatty acid accumulation. Cerebral energy metabolism was investigated in rats with the unilateral brain injury produced by the combination of left carotid artery ligation and systemic exposure to hypoxia. ATP and phosphocreatine levels in the left hemisphere were progressively reduced after the hypoxic-ischemic insult. The reduction of high-energy phosphate levels was accompained by an increase in sodium content and a decrease in potassium content. Mitochondria isolated from the damaged hemisphere showed a defect in ATP formation and oxygen uptake with a reduced ATP/O ratio. A large amount of free fatty acids (palmitic, stearic, oleic and arachidonic acids) accumulated in the injured hemisphere. The addition of unsaturated fatty acids (including oleic and arachidonic acids) to mitochondrial preparations caused an impairment of oxidative phosphorylation similar to that observed in mitochodria isolated from the damaged hemisphere.


Strength-duration analysis of the organization of reinforcement pathways in the medial forebrain bundle of rats. Strength-duration curves were determined for electrical self-stimulation of the brain in rats implanted with lateral hypothalamic electrodes. The rats self-stimulated in different behavioral situations which required them to make different responses, and the parameters of the strength-duration curves determined in each situation were compared. The comparisons suggested that two distinct groups of neurons were involved in the mediation of brain stimulation reinforcement of the bar pressing response, and that one of these groups was primarily involved in mediating the reinforcement of an alley running response, while the other group primarily mediated the reinforcement of a responses suggested that the nature of the response a rat is response a rat is required to perform determines the exact combination of neurons from the two groups which participate in mediating the brain stimulation reinforcement of the task. The possible functional significance of these two neuron groups was discussed.


The growth of the dendritic trees of Purkinje cells in the cerebellum of the rat. The growth of Purkinje cell dendritic trees in the cerebellum of the rat was studied over the first 50 days of life, using the technique of network analysis and the Golgi-Cox impregnation method. Our findings showed that a growth spurt occurred from the 10th to 30th day post partum (pp) and involved the production of a massive number of branches of fairly constant length. Growth of the tree occurred firstly in the lateral domain, so that by 15 days pp most trees were of adult width. Thereafter, increases in height occurred until 30 days pp. Associated with this change in direction of growth, from the mainly transverse to the vertical plane, was a deviation from the normal random pattern of branching of the tree, but this was reestablished when reorientation was complete, and growth in the vertical plane underway. The lengths of proximal segments increased once they had become established, but distal branches probably maintained a constant length. The above results, together with changes in segment length, trichotomy, branching probability, and growth cone morphology during development have been discussed in relation to current concepts of dendritic growth.


Cholinesterase activity and choline uptake in intact nerve cell cultures. Choline uptake and ecto-cholinesterase activities have been measured in intact astroblast and neuroblast cultures. The data show that choline uptake is dependent upon the ionic composition of the culture medium and is sensitive to metabolic inhibitors. However, the high concentrations of the inhibitors necessary for the inhibition of the uptake and some thermodynamic properties qould suggest a facilitated transport rather than an active uphill process. Preincubation of the cultures with various inhibitors of cholinesterases shows no direct parallelism between inhibition of choline high affinity uptake (apparent Km approximately equal to 10-6 M) and inhibition of ecto-acetylcholinesterase (EC 3.1.1.7).


An aberrant crossed visual corticotectal pathway in albino rats. This study investigates the dynamic nature of the developing corticotectal pathway arising in the visual cortex. Special attention is given to the interaction occurring between the corticotectal pathways of each side of the brain and between corticotectal and retinotectal terminations. Normally the visual cortex of rats projects only to the ipsilateral superior colliculus. If one visual cortex is removed at birth, the remaining visual cortex subsequently shows a bilateral projection to the superior colliculus. The aberrant corticotectal pathway is heavier if the cortical ablation is accompanied by eye removal at birth but eye enucleation alone is not a sufficient stimulus for production of a crossed corticotectal projection. The aberrant crossed pathway shows a topographic order which appears to correspond to that of the normal ipsilateral corticotectal pathway. The pathway differs from the aberrant projections from the retina in that lesions done as late as 20 days postnatal still result in an aberrant crossed corticotectal pathway. This is similar to the aberrant crossed cortical projections from sensorimotor cortex. The pathway would appear to arise as a result of lack of competition from corticotectal axons normally present contralaterally or from attraction of denervated corticotectal sites. While denervated retinotectal sites stimulate sprouting of the corticotectal axons once in the deafferented colliculus, they do not stimulate crossing of the corticotectal projection.


The role of suprachiasmatic nuclei of the hypothalamus in the production of circadian rhythm. (1) Action potentials were recorded from single neurons in suprachiasmatic nuclei of hypothalamus in urethane anesthetized male rat. The rate of firing ranged from less than 1 to over 10/sec but was generally 4-8/sec, and it varied from one cell to another in the same animal. (2) Repetitive stimulation of optic nerve or light acting on the eye augmented the activity of approximately half of the the suprachiasmatic neurons examined (67 out of 159 cells) while 37 neurons (23%) showed clear inhibition by the same stimuli. (3) Stimulation of the suprachiasmatic nuclei strongly inhibited the electrical activity of cervical sympathetic nerves. Light or optic nerve stimulation also inhibited activity of cervical sympathetic nerves. (4) The rate of discharge of suprachiasmatic nuclei showed, at times, some short duration oscillations occurring every 3-5 min, but at other times the same neuron showed a steady low frequency of firing. (5) Projection of optic nerves to the suprachiasmatic nuclei was demonstrated by anterograde migration of horseradish peroxidase placed in the vitreous body. (6) It was suggested that light excites certain groups of neurons in the suprachiasmatic nuclei which exert inhibitory action on cervical sympathetic nerve. This, in turn, caused a reduction in norepinephrine release by nerve fibers innervating the pineal and a reduction in pineal enzyme production. Thus, neurons in these nuclei contribute to the suppression of pineal enzyme production produced by light.


Transfer characteristics of first and second order lateral canal vestibular neurons in gerbil. Discharge patterns of first and second order vestibular neurons responding to angular acceleration in the plane of the lateral canals were studied in gerbil. The resting discharge activity of each cell was used to characterize the neuron by measureing the coefficient of variation and coefficient of skewness of the interspike interval distributions. Sinusoidal angular oscillations ranging in frequency from 0.0125 to 5.0 Hz were delivered by a velocity controlled rate-table. A PDP-12 minicomputer system was used on-line to display period and post-stimulus histograms of discriminated single unit activity. Off-line Fourier analysis of the period histograms was used to determine the phase of cell response to sinusoidal accelerations, while the average level and amplitude were determined by a least squares fitting algorithm applied over the fraction of the stimulus period where the cell discharged. First order neurons were found to have high discharge rates (average = 61.7 imp./sec) and bidirectional responses to rotation, and were of two groups called regular and irregular according to their resting discharge patterns. Second order neurons, located mainly in the medial and lateral vestibular nuclei, had low or even zero resting discharge rates (average = 17.8) resulting in more uni-directional responses and were of a single population. For frequencies less than 10 Hz, the Bode plots of the regular first order neurons are similar to that of a first order system with a time constant of about 2 sec as predicted by the torsion pendulum theory for cupula movement. The irregular first order neurons show an increasing gain above 0.5 Hz and a large phase lead relative to angular velocity above 1.0 Hz suggestive of a fractional power transfer function. The second order neurons show the phase and gain characteristics of the regular first order neurons being in phase with angular velocity above 1.0 Hz.


Characteristicas and response differences to iontophoretically applied norepinephrine, D-amphetamine and acetylcholine on neurons in the medial and lateral vestibular nuclei of the cat. Midcollicular decerebrate cats, with their cerebellum removes, were tested with controlled acceleratory motion in order to identify neurons in the medial vestibular nucleus (MVN) and lateral vestibular nucleus (LVN) which responded to a motion stimulus. Five-barredled micropipettes were used to record single neuron activity and to apply norepinephrine (NE), d-amphetamine and acetylcholine (ACh). These agents were  studied on spontaneously firing cells which responded to a motion stimulus and others which were in the MVN were inhibited by NE and d-amphetamine but were unaffected by iontophoresis of the alpha-adrenergic blocking agent phentolamine or the beta-antagonists, MJ-1999 or propranolol. In the LVN a majority of the cells tested were excited by NE and d-amphetamine. NE excitation in the LVN was antagonized by phentolamine but not by MJ-1999 or propranolo. Cats pretreated with reserpine to deplete brain catechlamines showed typical responses to NE BUT IONTOPHORESIS OF D-AMPHETAMINE WAS WITHOUT EFFECT. Unlike the differential sensitivity observed for NE, ACh excited most cells in both the MVN and LVN. NE and ACh produced similar responsed on vestibular neurons modulated by motion and those not responsive to motion. These observations suggest that NE-containing terminals are in close proximity to the vestibular neurons which were tested and further implicate both NE and ACh as neurotransmitters in afferent pathways to the vestibular nuclei.


Systems of measurement: their development and use in medicine. A brief historical review of customary measurements, the resultant chaos and the desirability for a simplified unified measurement system is discussed. The basic units of the International System of Units are described and defined, along with their application in Medicine.


Cardiac arrests in the operating room-Part I. (1965-1974). A ten-year review of the incidence of cardiac arrest in the operating suite at the St. Boniface General Hospital has been presented. Seventy cardiac arrest occurred during this period, and 29 were permanently resuscitated for a survival rate of 41.4 per cent. This rate compares favourably with the published experince of other centres. It does not, however, reflect an improvement over the survival rates published prior to 1960, a point in time when direct cardiac compression for the management of these cases was virtually abandoned in favor of external cardiac compression. To improve survival, a plea is made for return to early use of thoracotomy and direct cardiac compression in the treatment of cardiac arrest in the operating room. To accomplish this end all surgeons and anaesthetists should become familiar not only with the techniques required for these procedures, but also with the prevention and management of any associated complications.


Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man. Ventilatory responses to CO2 (delta VI/delta PCO2) were measured half, one, two and four hours after infusions of thiopentone, morphine, fentanyl and saline in healthy men in order to test the idea that variation in clinical recovery and control of breathing after anaesthetic drugs are associated with interindividual differences in control measurements of delta VI/delta PCO2. Ventilatory response to CO2 was profoundly reduced one half hour after each drug, in contrast to the observation during air breathing that ventilation and end tidal PCO2 had returned to within 10 per cent of control. Mean delta VI/delta PCO2 increased progressively at one, two, and four hours, returning to near control after thiopentone, but remaining less than 80 per cent of control four hours after morphine and fentanyl. From the regression equations of each ventilatory response, ventilation at PCO2 of 58 and 70 mmHg (VI58 and VI70) were computed to estimate displacement of the response curves by the drugs. Following thiopentone there was no significant change of V158. In contrast ther was a highly siginificant fall of VI58 one half hour after fentanyl (p less than 0.01), with progressive return towards control at one, two, and four hours; similar changes were observed after morphine. For each drug, changes of VI70 were substantially greater than corresponding changes of V158. At all times during these recovery measurements, subjects were conscious and co-operative and, by traditional clinical criteria, were judged to have recovered from the effects of the drugs. Differences between high and low responding subjects were assessed by plotting control measurements against values obtained half and one hour after drugs. No systematic differences were found. These findings suggest that delta VI/delta PCO2 is a sensitive indicator of central nervous activity, but do not support the concepts that individuals with low delta VI/delta PCO2 might be more susceptible to the ventilatory depressant effects of anaesthetic drugs, or that low delta VI/delta PCO2 might be associated with delayed return of spontaneous breathing after general anaesthesia. Plasma thiopentone levels at half, one, and four hours were highly reproducible, in contrast to the wide variation of delta VI/delta PCO2 among subjects in this study. These findings together support the notion that wide variation in clinical recovery from anaesthesia may have a primary physiological basis in addition to variation caused by interindividual differences in drug dosage, biotransformation and excretion.


Changes in plasma potassium and calcium levels and in the electrocardiogram after a single dose of succinylcholine preceded by d-tubocurarine. One hundred and eighteen patients undergoing surgical procedures not requiring immediate tracheal intubation, nor producing visceral reflexes, were pretreated with d-tubocurarine 6 mg, three minutes before the administration of a bolus of succinylcholine (2 mg/kg). Electrocardiographic changes, venous and arterial plasma potassium and calcium levels, CPK changes (12 patients) and appearance of myoglobinuria (35 patients) were followed. Pretreatment with a small dose of d-tubocurarine did not change the overall incidence and pattern of arrhythmias; it did, however, prevent increases in plasma potassium in 90.4 per cent of the patients, mean plasma potassium values remaining below pre-induction levels. The CPK level changed in only one of 12 patients (from 10 to 21 I.U., the normal range being 0 to 34 I.U.). No myoglobinuria was detected in any of the patients tested. A rapid but short-lasting change in the K+/Ca++ ratio did not seem to influence the occurrence of arrhythmias. Pretreatment with a small dose of d-tubocurarine is effective in preventing or decreasing fasciculations, plasma potassium and CPK changes and myoglobinuria described after the intravenous administration of succinylcholine. The already useful role of succinylcholine in our armamentarium can be made safer by pretreatment with a small dose of d-tubocurarine.


The cardiovascular effects of diazepam and of diazepam and pancuronium during fentanyl and oxygen anaesthesia. The cardiovascular effects of diazepam 0.5 and 1.0 mg/kg and diazepam with pancuronium 0.1 mg/kg after fentanyl 0.5 mg/kg were determined in thirteen dogs premedicated with atropine. Fentanyl produced significant reductions in heart rate, cardiac ouptut and arterial blood pressure. Administration of 0.5 mg/kg of diazepam after fentanyl did not significantly alter stroke volume, arterial blood pressure or peripheral vascular resistance but did increase heart rate and cardiac output. Additional diazepam did not further change the heart rate, but did reduce stroke volume, cardiac output, arterial blood pressure and peripheral vascular resistance. Administration of pancuronium after fentanyl and diazepam produced marked elevations in heart rate, cardiac output and arterial blood pressure. There was no difference in mean heart rate and cardiac output when values prior to fentanyl and those obtained three minutes following pancuronium were compared. These data demonstrate that large doses of fentanyl decrease heart rate, cardiac these changes can be partially reversed with diazepam 0.5 mg/kg and completely antagonized with pancuronium 0.1 mg/kg.


Pulmonary resistance and methods of humidification in acute pulmonary failure. In order to evaluate the effects of ultrasonic nebulization on airway resistance in respiratory failure, ten patients requiring mechanical ventilation for acute pulmonary failure were each ventilated with two humidification systems, one producing inspired air saturated with vapour at 35 degrees C, the other nebulizing water droplets ultrasonically. There was no statistically significant difference in pulmonary resistance at inspiratory flow rates of 40, 60, AND 80 1/min. A separate comparison between humidifiers in those patients with the highest resistances did not reveal any difference in response to method of humidification. In contrast to studies in other contexts, these data fail to show any significant difference, from the standpoint of effects on resistance, in the use of ultrasonic mist humidification during mechanical ventilation for respiratory failure.


Anaesthesia for separation of conjoined twins. We have presented the anaesthetic technique used during the separation of two female pygopagus conjoined twins. The twins were three months old and weighed 9.2 kilograms on the day of the operation. The main problem during the operation was to evaluate blood volume lost by each patient and a close monitoring of all cardiovascular parameters was necessary to attain this aim. The little pygopagus recuperated well and left the hospital at six months old.


Spontaneous breathing with the Bain circuit at low flow rates: a case report. A clinical case is presented which suggests that spontaneous respiration with the Bain circuit at low flow rates is associated with rebreathing. Controlled ventilation is advised when the Bain circuit is used.


An unusual complication after stellate ganglion block by the paratracheal approach: a case report. A case is presented of repeated stellate ganglion block using the paratracheal approach at the level of C6 and using the low dose method. Subarachnoid spread of local anaesthetic resulted in total spinal block below the level of C4. The potential hazards of this techinque of stellate ganglion block and methods of avoiding them are discussed, together with the possible mechanism in this case.


Paraplegia following transurethral surgery. We have presented a case of paraplegia following spinal anaesthesia administered for a transurethral prostatic resection. Further investigation revealed a metastatic peridural compressive lesion at the level of T4. We have discussed some of the contributory factors involved, chiefly the lumbar puncture (perimedullary vascular engorgement, alterations in C.S.F. dynamics) and the possible role of intra-operative water intoxication (swelling of spinal cord cells).


Bone metastases from breast cancer at the time or radical mastectomy as detected by bone scan. Eight-year follow-up. Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.


Observations following Corynebacterium parvum administration to patients with advanced malignancy. a phase I study. There has been increasing interest regarding the use of Corynebacterium parvum (CP) with other modalities in the management of primary cancer. Due to the paucity of specific information available relative to CP toxicity, a Phase I study was carried out in patients with advanced disease. The purpose of the investigation was not to evaluate the effect of CP on tumor growth. from 273 injections of CP in 40 patients it was observed that following intravenous (i.v.) infusion of CP: a) a febrile response and chills of considerable severity occured in almost all patients and did not appreciably diminish in intensity following repetitive administrations; b) nausea, vomiting, headache, and confusion were not infrequent; c) a "flu-like" syndrome lasting 24 to 48 hours occurred following almost all courses of CP; d) blood pressure elevations occurred on occasion and were related  to the severity of other-side-effects; hyper- or hypo- tension was not a problem; e) ther were no anaphalactic reactions. Pretreatment with a single administration of 100 mg of hydrocortisone prior to CP infusion markedly and in some instances dramatically diminished the toxicity and made acceptable the use of i.v. CP on an outpatient basis. The use of i.v. CP in patients with cerebral metasteses may be hazardous. Subcutaneously administered CP resulted  in a significant number of undesirable local reactions. Evaluation of delayed cutaneous hypersensitivity response, immunoglobulins, complement, and E- and EAC-rosette-forming cells during CP administration failed to demonstrate significant change from injection values. Results were similar whether hydrocortisone pretreatment was or was not employed. From the standpoint of toxicity it now seems appropriate to use i.v. CP, particularly following pretreatment with hydrocortisone, in a controlled clinical trial to evaluate its therapeutic effectiveness in the management of primary cancer.


Combination chemotherapy and adriamycin in patients with advanced breast cancer. A Southwest Oncology Group study. In January, 1972, the Southwest Oncology Group initiated two randomized studies for patients with advanced breast cancer. The study for patients with prior chemotherapy showed a 33% response rate with adriamycin. The study for patients without previous chemotherapy consisted of three treatment regimens; a weekly repeated combination of cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone; these same five drugs given in courses of 5 days repeated every 4 weeks; and adriamycin as a single agent every 3 weeks. For the 283 evaluable patients, the response rates were: weekly combination 63/106 (59%); intermittent combination 39/98 (40%); and adriamycin 31/79 (39%). The median duration of response was 8 months for weekly combination, 10 months for intermittent therapy and only 4 months for adriamycin. Leukopenia was the dose-limiting toxicity with all three regimens. The weekly combination is the most effective therapy for patients with advanced disease. Extensive trails of combinations that include adriamycin are underway.


Immune evaluation with skin testing. A study of testicular, prostatic, and bladder neoplasms. Fifty patients with testicular carcinoma, 45 with prostatic neoplasm, 84 with bladder carcinoma, and 13 with benign bladder papilloma were evaluated for skin reactivity to DNCB and other intradermal antigens. Correlation between pathologic staging and skin-test reactivity was sought. Reaction to DNCB among patients with testis tumors was more significantly depressed by chemotherapy than by the extent of retroperitoneal or distant metastatic disease indicating that skin testing as a means of following the course of disease or of predicting survival may be limited by alterations caused by chemotherapy. DNCB reactivity did not correlate with the prognosis for the different stages of disease, but follow-up studies of individual patient survival are needed for substantiation. Depression of DNCB reactivity exists among patients with prostatic carcinoma whether the disease is localized or widely metastatic. Only lengthy follow-up will determine if there is any correlation of reactivity with survival in individual patients. DNCB reactivity among patients with bladder tumors shows progressive reduction with increasing stage disease and lends support to the evidence suggesting immune deficiency in patients with bladder neoplasm.


Ultrastructure of the esthesioneuroblastoma. A tumor in the anatomic location and with the light microscopic appearance of an esthesioneuroblastoma was examined with the electron microscope. Secretory-type granules, cytoplasmic fibrils, and microtubules similar to those described in neuroblastomas were found in many of the tumor cells, which supports an origin from the sympathetic autonomic nervous system. Similar organelles were found in three other nasal tumors considered to be esthesioneuroblastomas, but their detail was obscured because they were examined after being initially processed in paraffin.


Comparative ultrastructure of tubular carcinoma and sclerosing adenosis of the breast. The innocuous histologic appearance of tubular carcinoma of the breast and its superficial histologic resemblance to sclerosing adenosis will occasionally present diagnostic problems. A comparative ultrastructural analysis of two tubular carcinomas and three cases of sclerosing adenosis was made that showed definite differences in the pattern of myoepithelial cell differentiation and basal lamina deposition in these two entities. Prominent myoepithelial cells and basal lamina reduplication were both conspicuous features of sclerosing adenosis that appeared to be absent in tubular carcinoma. Intracytoplasmic "pseudocysts" were frequently found in sclerosing adenosis, but not in tubular carcinoma. Conversely, intracytoplasmic lumina and incomplete tubular structures were present in tubular carcinoma and seemingly absent in sclerosing adenosis. Such basic ultrastructural differences may help to differentiate these two mammary lesions when diagnostic problems occur at the conventional light microscopic level.


Melanoma. Tumor angiogenesis and human neoplasia. Transparent hamster-cheek-pouch chambers were used to document angiogenesis induced by implants of human malignant melanoma. Capillary proliferation was observed with direct implantation of melanoma fragments and with tumor implants place on microporous membrane filters. The pattern of capillary neovascularization was recorded and correlated with clinical and histopathologic parameters.


Monomorphic adenomas of salivary glands. Trabecular-tubular, canalicular, and basaloid variants. Eleven cases of monomorphic adenoma of the salivary glands are interpreted as variants of pleomorphic adenomas (mixed tumors) that lack chondroid or myxomatous components. Nine of these tumors were in the parotid gland and two were on the hard palate. Monomorphic adenomas are usually encapsulated and frequently are partially cystic. Their histologic pattern may be confused with that of adenoid cystic carcinoma, but they grow in an expansile fashion and usually are monolobular. Histologically, they may be divided into trabecular-tubular, canalicular, and basaloid variants. Morphologically, they bear a resemblance to basaloid sweat-gland tumors (eccrine spiradenoma and cylindroma).


Urinary amino acid excretion in acute leukemia. Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.


The clinical usefulness of serum copper determinations in Hodgkin's disease. A retrospective study of 241 patients from 1963-1973. Serum copper determinations were routinely performed in 141 men and 100 women with histologically verified Hodgkin's disease, admitted to the Radium Centre for Jutland over a 10-year-period from January 1, 1963, to January 1, 1973. The previously described variations in serum copper with the activity of the disease, increasing with progression and decreasing with improvement, were amply substantiated. Furthermore, the present study showed that the serum copper value at the first admission, before treatment, is statistically significantly correlated to the stage of the disease and consequently probably to the amount of tumor tissue. In men there was also a statistically significant correlation of se Cu to the histologic grade of the bioptic material (classification according to Lukes 1966). In women the correlation was blurred by the effect on serum copper of estrogen, mainly from contraceptive pills and pregnancy. The serum copper is regularly reduced to within normal limits at complete remission; thus, it is proposed that this parameter be included in the criteria for complete remission.


Gastric carcinoma with lymphoid stroma. Its morphologic characteristics and prognostic correlations. A type of gastric carcinoma was specified under the designation carcinoma with lymphoid stroma. Grossly, this carcinoma was characterized by clear circumscription, usually with a central ulceration. A histologic feature distinguishing this carcinoma was the presence of a nondesmoplastic stroma infiltrated uniformly with an abundance of lymphocytes and plasma cells throughout the entire area of the tumor. Sparse population of less pleomorphic cancer cell nests of thin trabecular, microalveolar, or primitive tubular pattern widely separated by the intervening stroma was another feature peculiar to this tumor. Carcinoma of this type was found in 4% of a total of 1041 cases of gastric carcinoma removed surgically. A high survival rate was noted among the patients undergoing surgery for this carcinoma. A proposal was made on the separate classification of this tumor from common gastric carcinomas.


Perspectives on the use of microspectrophotometry in the diagnosis of pretumorous processes and malignant tumors. Comparative microspectrophotometric study of the nuclear Feulgen DNA content in pretumorous processes and cancers (larynx, endometrium, large intestine, and stomach) has made it possible to formulate an exponential law of DNA accumulation in cell populations in proliferating and malignant tissue. The dynamics of changes in the "index of DNA accumulation" can be used as an objective quantitative diagnostic test. A scale of malignant transformation was proposed with which the degree of probability of malignancy in pretumorous processes could be estimated. The data obtained allowed the author to propose a hypothesis of DNA superproduction as the basic cause of progressive neoplastic growth.


Lymphoma of the thyroid. An unusual clinical course in a patient possessing a 14/21 translocation. The unusual course of a lymphoma in a woman with a chromosome abnormality is reported. When aged 30 years, the right lobe of her thyroid gland was found to be infiltrated by a follicular lymphoma. Two years later, poorly differentiated diffuse lymphoctic lymphoma recurred locally, grew rapidly, and infiltrated the adjoining muscles. It was treated by widefield irradiation of the upper trunk and neck, and disappeared completely. The patient remained sympton-free for 22 years. Unequivocal Hodgkin's disease then developed in a left cervical lymph node; the patient received radiotherapy. Eighteen months later the right inguinal nodes were infiltrated by similar tumor and further treatment was given. Massive abdominal involvement followed and the patient died 28 years after developing the thyroid lymphoma. The tumor at necropsy was pleomorphic and contained Reed-Sternberg cells. The significance of the constitutional chromosome abnormality, a Robertsonian translocation of the No. 14 chromosome, is discussed.