Pathogenesis of paracoccidioidomycosis: A histopathological study of the experimental murine infection

The pathogenesis of primary pulmonary P. brasiliensis infection, the systemic dissemination which followed, and the histopathology of the main organs involved was studied in a murine model of chronic paracoccidioidomycosis. Adult male BALB/C mice, were challenged intranasally with 26×10^–6 viable P. brasiliensis yeast cells. We inoculated 86 animals which were sacrificed from 0 h to 20 weeks. As controls, 11 mice were instilled with saline solution, and 48 with 26×10^–6 heat-killed. P. brasiliensis yeast cells. None of the animals receiving saline, exhibited pathologic alterations; 11.6% of those inoculated with the heatkilled cells, revealed mild, transitory acinopulmonary neutrophilic infiltrates. The animals infected with viable cells, developed a systemic process affecting mainly the lungs (46.5%), liver (18.6%), lymphnodes (18.6%), and spleen (3.5%). In this group of animals, lung lesions were detected regularly at all time periods from 3 h to 20 weeks. A multiple bronchoneumonic process was initially observed at 6 h, reached its maximum intensity around the third day, subsided thereafter but did not disappear and reactivated after the fifth week to become stationary until the end of experiments. Dissemination to other organs occurred early, and apparently by the hematogenous route. Initially the inflammatory cell infiltrate was mainly neutrophilic. With time, these cells were gradually replaced by lymphocytes, histiocytes and plasmocytes. Granuloma configuration of the cell infiltrate was distinctly seen around the fifth week, with multinucleated giant cells appearing at the ninth week. Hiliary lymphnode involvement was rare (7%) and primary lung lesions, as seen in tuberculosis and histoplasmosis, were not observed.     

Gene distribution and nucleotide sequence organization in the human genome

Human DNA was fractionated by centrifugation in Cs2SO4 density gradients containing 3,6-bis(acetatomercurimethyl)dioxane (BAMD). Fractions were investigated in their analytical CsCl profiles and a number of specific sequences were localized in them. The results so obtained led to an improved understanding of the organization of nucleotide sequences in the human genome, as well as to the discovery that a class of DNA having a very high G + C content and not represented in the mouse genome, is particularly rich in genes and interspersed repetitive sequences.     

Cholinergic nerves in the human liver

Summary The cholinergic innervation of the human liver was studied. Slices (150–200m thick) of human liver and of the greater hepatic blood vessels (hepatic artery and vein, portal vein) were incubated in a solution of 6-hydroxydopamine (6-HDA) in order to obtain a selective degeneration of adrenergic nerves. Controls were prepared from samples incubated with buffer alone. The slices were cut on a cryostat into 15–20m thick sections and processed for the histochemical detection of cholinesterases.Cholinergic nerve fibres innervate the extra hepatic and the intrahepatic branches of the hepatic artery, the portal vein as well as the hepatic vein. Fewer cholinergic fibres innervate the hepatocytes and the hepatic sinusoids. The 6-HDA treatment does not seem to alter the pattern of the cholinergic innervation of the liver. The findings indicate the presence of a cholinergic parasympathetic innervation in the human liver.     

The 11q;22q translocation: A European collaborative analysis of 43 cases

Summary Translocation between the long arms of chromosomes 11 and 22 is usually detected in offspring with an unbalanced karyotype following a 3:1 disjunction resulting in partial trisomy. Since by the end of 1976 it was suspected that this translocation might be more frequent than one would deduce from published reports, it was decided to call for a collaborative effort in Europe to collect unpublished cases. In response, 42 cases were collected in Europe, and one case from New Zealand was added. The following countries were represented with the number of cases indicated in parentheses: Czechoslovakia (2), Denmark (4), Finland (3), France (6), Germany (1), Italy (5), The Netherlands (9), Sweden (6), United Kingdom (4), Yugoslavia (2). The wide geographical distribution indicates a multifocal origin of the translocation. Among the unpublished cases, 31 were ascertained as unbalanced carriers [47,XX or XY,+der(22),t(11;22)] and 12 as balanced balanced carriers [46,XX and XY,t(11;22)]. Among the published cases, 10 were ascertained in unbalanced and 3 in balanced carriers. The breakpoints of the translocations indicated by the contributors varied, the most frequently reported being 11q23;22q11 (25 cases), followed by q25;q13 (10 cases). While the first one seems more likely, it was not possible to decide whether the breakpoints were the same in all cases.All 32 probands with unbalanced karyotypes had inherited the translocation, 31 from the mother and only 1 from the father. This ratio became 43:1 when the published cases were added. A segregation analysis revealed that in families ascertained through probands with unbalanced karyotypes there was a ratio of carriers to normal (all karyotyped) 54:55, not a significant difference. The formal maximum (minimum) recurrence risk for this unbalanced translocation was calculated to be 5.6% (2.7%). When the ascertainment was through a balanced proband, the maximum risk was 2.7%. The risk was calculated as 5.7% for female and 4.3% for male carriers. The mean family size was 1.67 for the offspring of female carriers and 0.78 for the offspring of male carriers. This significant difference suggests that heterozygosity for the translocation reduces fertility in males. Indeed, several of the probands with balanced karyotypes were ascertained because of sub- or infertility. Only 2 de novo translocations were found among the 59 probands, and both, were among the 12 cases ascertained as balanced carriers. The source, quality, and quantity of the clinical data for the subjects with unbalanced karyotypes were variable, and no definite conclusions were possible about phenotypes. The following signs were recorded in 10 or more of the 45 cases: low birth weight, delayed psychomotor development, hypotonia, microcephaly, craniofacial asymmetry, malformed ears with pits and tags, cleft palate, micro-/retrognathia, large beaked nose, strabismus, congenital heart disease, cryptorchidism, and congenital dislocation of the hip joints. Many signs were similar to those considered typical of trisomy 11q, and the phenotype coincided almost completely with the presumptive phenotype of complete trisomy 22. No cases with coloboma was recorded, while other signs of the cat-eye syndrome were found in several probands. This might indicate that individuals with the cat-eye syndrome and carriers of the unbalanced 11/22 translocation have the same segment of 22 in triplicate plus or minus another chromosome segment.     

Chemical oxygen demand reduction in a whey fermentation

Summary Preparations of living Pseudomonas denitrificans cells immobilized in alginate gel were used in the denitrification of water. In the presence of an exogenous carbon source the entrapped microorganisms reduced nitrate and nitrite to gaseous products and to achieve complete reduction, carbon to nitrogen ratios of over two were required. The effects on denitrification of particle size and the number of bacteria in the gel were investigated. Apparent K_m values for nitrate and nitrite reduction were calculated for free and immobilized cells. When the immobilized cells were incubated in nutrient media, an increase in reduction rate was observed and this was shown to be caused by the growth of cells within the gel particles. Immobilized P. denitrificans cells retained 75% of their initial nitrate reduction capacity after 21 days of storage at +4°C. The operational stability of the alginate-immobilized cells was studied both in batch and in a column which was operated continuously. A column (45 g of alginate-cell fibers in 80 ml) denitrified a high nitrate drinking water (100 mg NO₃/l) with a rate of 300 ml of nitrate and nitrite free water/day/g of gel. The half life for nitrate reduction was estimated to be 30 days.     

Low-Angle Light Scattering of Deoxyribonucleic Acid

An instrument of new design has been built in order to perform lowangle light-scattering measurements to angles as low as 16°. Native deoxyribonucleic acid preparations of different molecular weights have been studied using this apparatus with a new clarification technique. The molecular weights obtained from the low-angle data have been compared with those calculated for the same samples when using the results in the 30-150° range. The two sets of data yield the same molecular weights up to values of about 6 × 10⁶. Higher molecular weights are underestimated to a variable extent when measurements in the usual angular region (30-150°) are used.     

ULTRASTRUCTURE OF ISOLATED KIDNEY MITOCHONDRIA TREATED WITH PHLORIZIN AND ATP

Direct electron microscopic evidence is reported of the ultrastructure of mitochondrial membranes and compartments in mitochondria isolated in 0.5 M sucrose from the rat kidney cortex and the experimental changes they undergo with phlorizin and ATP treatment. A heterogeneous population of mitochondria is recognized under control conditions. The mitochondria appear to be of 3 main types, normal, swollen, and contracted. Under phlorizin treatment, most of the mitochondria swell in less than 15 minutes, apparently at the expense of the matrix. Treatment with ATP, on the other hand, produces, during the same time, a marked contraction of the isolated mitochondria, with many refoldings of the inner membrane and marked increase in the electron opacity of the matrix. It is concluded from these observations that mitochondrial swelling and contraction should be related mainly to the matrix content.     

Synchronous Assisted Circulation

A summary of the work in synchronous assisted circulation undertaken at the Tufts-New England Medical Center Hospitals for the past year is presented.Counterpulsation, introduced in 1958, reduces myocardial oxygen consumption and increases coronary flow. It was applied to seven patients with terminal cardiogenic shock: one patient survived and three showed temporary improvement.The synchronous external assist makes possible control of the blood volume distribution, increases the cardiac output and decreases the pressure work of the left ventricle. The procedure does not require cannulation of the vascular system and is atraumatic.The same concept has been applied to the right ventricle using synchronous respiration.An “in-series” subcutaneously exteriorized prosthetic left ventricle, capable of long-term left ventricular assist, is under development. The device can atrialize the left ventricle. It requires no intracorporeal source of energy.This program offers hope for the development of effective temporary and long-term circulatory-assist procedures.     

Pools of water in anhydrobiotic organisms: A thermally stimulated depolarization current study

The ability to survive the removal of water in anhydrous biosystems is especially remarkable as a departure from the manifold structural and functional dependences on the presence of H₂O molecules. Identifiable pools of water present in dry soybean axes were investigated by means of the thermally stimulated depolarization current method. Samples were examined in the temperature range 100-340 K and over water contents (h, in gram H₂O per gram sample dry weight) ranging from h = 0.05 to 0.30 g/g. Three water-dependent relaxation mechanisms were detected; one attributed to dipolar reorientation of H₂O molecules hydrogen-bonded to other water molecules, one to reorientation of CH₂OH groups, and one to a glass transition in sugar-water domains. These glassy domains can protect intracellular components against destruction in the dehydrated state. Interestingly, protecting glassy domains were not found in dehydration intolerant seeds, supporting the hypothesis that the ability to withstand dehydration is associated with intracellular glass formation. A model for the state of cell water at interfaces is proposed.