Influence of basic fibroblast growth factor on the development of cholinoceptive neurons from fetal rat cerebrum in culture.

Neuronal cells from cerebral hemispheres of 14-day-old rats were grown for 6 days in a serum-free, chemically defined medium. About 95-98 and 3% of these cells were neurofilament and acetylcholinesterase (AChE)-positive, respectively. The addition of basic fibroblast growth factor (bFGF) at three developmental stages, i.e. at 4 h, 2 and 4 days resulted in an increase (about 2-fold) of the number of AChE-positive neurons. The enzyme reaction was present in the cell body as well as in the fibers, which often ramified extensively under the influence of bFGF. Treatment with bFGF after the 2nd day of culture had no or only a low stimulatory effect. Our findings indicate that bFGF affects the development of AChE-containing neurons, i.e. cholinoceptive neurons from rat cerebrum.


Thyroid hormone promotes transient nerve growth factor synthesis in rat cerebellar neuroblasts.

Primary cultures of cerebellum from 5-day-old rats indicated that proliferating neuroblasts synthesize and release nerve growth factor (NGF). Since NGF promotes DNA synthesis in these cells, our findings demonstrate that the early developing cerebellum is a suitable physiological model for studying the autocrine mitogenic action of NGF. Thyroid deficiency led to a greater reduction in the NGF content of the cerebellum than of the olfactory bulbs or hippocampus. Cerebellar NGF mRNA was also very sensitive to hormone deprivation. Physiological amounts of thyroid hormone stimulated both the mitotic activity and NGF production of cultured cerebellar neuroblasts. A lack of thyroid hormone is known to markedly alter cell formation in the cerebellum where postnatal neurogenesis is highly significant, in contrast to the olfactory bulbs and hippocampus. Taken together, these results suggest that the hormonal control of cell formation in the cerebellum is, at least partly, mediated by the autocrine mitogenic action of NGF. The thyroid hormone could temporally regulate the transient NGF synthesis by cerebellar neuroblasts directly and/or through its ontogenetic action, and hence all the NGF-dependent trophic effects.


Regulation of a beta-galactoside-binding lectin and potential ligands during postnatal maturation of rat brain.

Variations in expression and activity of a beta-galactoside-specific lectin were quantified during postnatal maturation of the rat brain. Lectin expression, estimated from enzymatic immunoassay data, and lectin activity, evaluated by rabbit erythrocyte agglutination, are higher in the brains of young animals (5 days after birth) than in older ones (2 months of postnatal life). Concurrently, modifications in glycosylation during cellular differentiation were detected by affinoblotting using a biotinylated derivative of a beta-galactoside-specific brain lectin. This study shows that membrane and cytosolic glycoconjugates of the rat brain bear appropriate beta-galactoside moieties which may be recognized by an endogenous lectin expressed in the tissue itself in relation to brain maturation. The observed variations in the expression of lectin and complementary glycoconjugates can be correlated with significant events of rat brain development.


Demonstration of segmental arrangement of thoracic spinal motor neurons using lipophilic dyes.

Unlike the afferent input into the spinal cord, it is generally believed that the motor efferent system in the mammalian spinal cord is more segmental in arrangement. Isolated comments in recent reports suggest that motor neurons in the mammalian spinal cord may be strictly segmental, contrary to many earlier reports using less sophisticated methods. We have attempted to address the question of the segmental arrangement of motor neurons in a mammalian spinal cord using single and double labelling with the fluorescent lipophilic dyes, Di I and Di A. These dyes have the ability to diffuse along and stain the plasma membrane of the neural elements in aldehyde-fixed specimens. Sprague-Dawley rat fetuses and early postnatal pups were used. The study was conducted on the thoracic spinal cord. The results confirm that thoracic spinal motor neurons are restricted to the segments from which their axons exit via the ventral roots in the intrauterine stages of development. The segmental arrangement of motor neurons in the thoracic spinal cord corresponded well with that of the sympathetic preganglionic neurons which were stained simultaneously.


Role of human microflora in health and disease.

The human host and its microbial flora constitute a complex ecosystem whose equilibrium serves as a remarkable example of reciprocal adaptation. Intestinal bacteria play an important role in the development of the immune system. The normal intestinal flora is responsible for resistance to colonization by exogenous pathogenic microorganisms. Nevertheless, it also constitutes a reservoir of potentially pathogenic bacteria in close contact with the host. These bacteria are responsible for opportunistic infections in immunocompromised hosts. The equilibrium of the flora can be upset by antibiotics, leading to infections as a result of proliferation of antibiotic-resistant pathogenic bacteria.


Resistance of anaerobic bacteria to antimicrobial agents in Spain.

As a consequence of antibiotic consumption, the entire microbial ecosystem attached to man is evolving towards resistance. In Spain, penicillin resistance (MIC > 0.5 mg/l) is found in about 10% of Peptostreptococcus, Clostridium perfringens and Eubacterium, and in 50% of Veillonella. Cefoxitin resistance ( > 2 mg/l) is present in 10 to 20% of Peptostreptococcus and Clostridium, and in 50% of Eubacterium; 21% of Bacteroides (fragilis group) strains are resistant to 16 mg/l. A very low rate of imipenem resistance (> or = 128 mg/l) is found among Bacteroides (1%), but for 5% of the isolates MICs of imipenem are 2 to 4 mg/l. Metronidazole resistance ( > 8 mg/l) is found in 5 to 10% of Peptostreptococcus, Clostridium and Veillonella, and in less than 1% of the Bacteroides fragilis group. Erythromycin resistance ( > 2 mg/l) is present in over two-thirds of the Peptostreptococcus, Veillonella and Fusobacterium isolates, and in 27% of the Clostridium perfringens strains. Clindamycin resistance ( > 4 mg/l) is found in 10 to 20% of the Peptostreptococcus, Clostridium and Eubacterium isolates, and in 20% of the Bacteroides of the fragilis group, this rate being higher (30%) among faecal isolates.


Clinical relevance of antimicrobial susceptibility testing.

In recent years, significant resistance to antimicrobial agents has been encountered among certain anaerobic bacteria. Susceptibility patterns vary from region to region, but even within a given region susceptibility is not always predictable. Initially, therapy of mixed anaerobic infections must be empirical, based on the nature of the infection, the usual flora of such infections, anticipated modification of this flora by pathophysiologic processes or prior antimicrobial therapy, and evaluation of Gram stains from appropriate specimens. If the infection does not respond well or the patient requires long-term therapy, antimicrobial susceptibility testing may be indicated in order to provide optimum therapy. Susceptibility testing is also indicated for determination of the usual patterns in a particular hospital, for monitoring geographical patterns, and to determine the activity of new antimicrobial agents.


Review of methods for susceptibility testing of anaerobes.

In the USA, the National Committee for Clinical Laboratory Standards has studied and published a reference agar dilution method for the susceptibility testing of anaerobic bacteria. While numerous investigators both in Europe and the USA have evaluated a variety of methods with a variety of modifications, only the broth microdilution method appears to be appropriate for routine use. The problems of the choice of breakpoint, inoculum size, media, media additives, endpoint recognition and other parameters affecting test performance and interpretation, while troublesome for anaerobes, are not unique to this group of organisms. The increasing resistance of anaerobes and the ever existing need to provide therapeutic guidance, surveillance for resistance and susceptibility data on new drugs make the need for an accurate and reliable susceptibility test for anaerobes critical. The newer methods, while showing promise, need further evaluation with all agents that have a therapeutic indication for anaerobic infections.


Methods for the isolation and identification of obligate anaerobes.

The methods used for the isolation and identification of obligate anaerobes often appear to be exactly the same as those used 20 years ago. However, careful evaluation of the methodology available reveals many improvements in technology. More importantly, the use of computerized instrumentation and new, non-growth-dependent methods for characterization suggest that in the next few years even greater changes will occur in systems for identification of this group of organisms.


Epidemiological aspects of infections caused by Bacteroides fragilis and Clostridium difficile.

Bacteroides fragilis and Clostridium difficile are two of the most common anaerobes associated with human disease. Studies on the epidemiology of Bacteroides fragilis are limited and are based predominantly on serogrouping, which suggests intraspecies differences. Further studies using newer techniques for typing are required to elucidate the epidemiological characteristics of this important pathogen. By contrast, numerous phenotypic, immunological and molecular methods have been developed for typing and fingerprinting of Clostridium difficile and applied in epidemiological studies to show conclusively that Clostridium difficile is nosocomially acquired and that there is transmission and cross-infection between hospital patients.


Clinical importance of Bilophila wadsworthia.

Bilophila wadsworthia is an anaerobic, gram-negative, asaccharolytic, urease-positive, bile-resistant, catalase-positive bacillus, originally recovered from infections in patients with gangrenous and perforated appendicitis. Additional isolations from clinical specimens, including pleural fluid, joint fluid, blood and pus from a scrotal abscess, mandibular osteomyelitis and axillary hidradenitis suppurativa are described here. Bilophila is found as normal flora in feces and, occasionally, in saliva and in the vagina. Isolates from humans are usually beta-lactamase positive and therefore resistant to certain beta-lactam antibiotics. Two percent of strains are also resistant to clindamycin.


Role of fibrin deposition in the pathogenesis of intraabdominal infection.

The production of fibrinous exudates plays an important role in determining the outcome of peritoneal infection. Large numbers of bacteria are sequestered within fibrin matrices, thereby retarding bacterial spread throughout the peritoneal cavity and into the bloodstream. This walling-off process is teleologically advantageous in that it lessens early rapid mortality. Recent studies have documented that this same process is probably integral to the development of residual infection in the peritoneum. Bacteria sequestered within fibrin deposits are protected from normal host clearance mechanisms, thereby permitting unopposed proliferation and ultimately the establishment of an abscess. A complete understanding of the cellular and noncellular aspects of the host response to peritoneal infection will suggest novel strategies both to treat and to prevent the development of intraabdominal abscesses and their attendant consequences.


In vitro susceptibility of clinical isolates of Bacteroides fragilis and Bacteroides thetaiotaomicron in Japan.

A nationwide survey of the susceptibility of 433 isolates of Bacteroides fragilis and 149 isolates of Bacteroides thetaiotaomicron was conducted from December 1986 through November 1989 in Japan. These strains were collected from 16 university hospitals and one metropolitan hospital. Metronidazole was the most active drug against both species, with no resistant isolates found. The activity of imipenem and sulbactam-cefoperazone was good, with very low resistance rates determined in Bacteroides fragilis (1.4% and 1.6%, respectively) and in Bacteroides thetaiotaomicron (3.4% for both drugs), and was comparable to that of metronidazole. Cefoxitin, cefmetazole, cefotetan, cefbuperazone, latamoxef and ceftizoxime were found to be more active against Bacteroides fragilis, for which resistance rates were 3.2 to 9.5%, than against Bacteroides thetaiotaomicron, for which resistance rates were 18.1 to 21.8%. Rates of piperacillin resistance in the two species were 12.9% and 26.8%, respectively. Clindamycin was very active at a low concentration (MIC50 of 0.39 to 1.56 mg/l), but 24% and 27.5% of Bacteroides fragilis and Bacteroides thetaiotaomicron isolates, respectively, were resistant to this agent.


German multicentre study on the in vitro susceptibility of Bacteroides species. The German Bacteroides Study Group.

In 1990 the first German multicentre study on the in vitro susceptibility of Bacteroides species was completed. Employing a commercially prepared microbroth dilution assay, nine participating institutions evaluated approximately 100 consecutive isolates of Bacteroides species from relevant clinical specimens. A total of 911 strains (449 Bacteroides fragilis, 201 Bacteroides thetaiotaomicron, 79 Bacteroides ovatus, 78 Bacteroides vulgatus, 77 Bacteroides distasonis, 25 Bacteroides uniformis, 2 others) were tested. Most of the isolates came from surgical patients (72%); other sources included gynaecological patients (9%) and medical patients (5%). Seventy-eight percent of the anaerobes were found in mixed culture together with at least one aerobic organism (Escherichia coli 36%, streptococci 15%, or enterococci 13%), while in 22% of the cases, the anaerobes were the only bacteria grown from the specimens. The results showed that many of the strains were potent beta-lactamase producers (as judged by resistance to amoxicillin). However, all but one of the isolates demonstrated susceptibility in vitro when clavulanic acid was added to amoxicillin or ticarcillin. At the same time, 13% of the organisms were resistant to mezlocillin, 5% to cefoxitin and 4% to clindamycin. Three strains were reported resistant to imipenem and one strain to metronidazole.


beta-Lactamase production and susceptibility of US and European anaerobic gram-negative bacilli to beta-lactams and other agents.

The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of the Bacteroides fragilis group and 51% of the non-Bacteroides fragilis group were beta-lactamase positive. Amongst the non-Bacteroides fragilis group, beta-lactamase positivity rates were higher for US strains (58%) than for European strains (39%). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all beta-lactamase negative strains were 0.5 and 2 micrograms/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin (> or = 256 micrograms/ml) and ticarcillin (> or = 64 micrograms/ml) to 16 and 8 micrograms/ml, respectively, for the Bacteroides fragilis group, and to 4 micrograms/ml for both agents for the non-Bacteroides fragilis beta-lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in the Bacteroides fragilis group, while 95 beta-lactamase producing strains (predominantly Bacteroides fragilis group and fusobacteria) did not show synergy between beta-lactams and clavulanate. Of the newe agents tested, meropenem and piperacillin-tazobactam were the most active (100% of strains susceptible), followed by amoxicillin-BRL 42715 (99% of strains susceptible); 94 to 98% of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, temafloxacin and clindamycin. Only 73% of the strains were susceptible to cefotetan, compared to 91% to cefoxitin; 88% of the strains were susceptible to trospectomycin. Overall, all of the beta-lactam/beta-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against beta-lactamase producing strains, while all agents tested had good activity against beta-lactamase negative strains.


Survey of the susceptibility patterns of Bacteroides fragilis group strains in France from 1977 to 1992.

Rates of antibiotic resistance within the Bacteroides fragilis group were monitored over a 15-year period in France by examining studies that employed the same methodology to test susceptibility of anaerobic bacteria. Chloramphenicol, metronidazole, beta-lactam/beta-lactamase inhibitor combinations and imipenem remained very active against Bacteroides fragilis. There was little or no change in rates of resistance to these antibiotics. Resistance to clindamycin increased from 1% in 1977 to a peak of 19% in 1987, and since then has remained at 8 to 12%. There was some evidence that resistance to most beta-lactam agents increased during the same period. These results emphasize the need for periodic surveys of resistance patterns of the Bacteroides fragilis group in each country.


Value of measurement of C-reactive protein in febrile patients with hematological malignancies.

The maximum serum levels of C-reactive protein (CRP) in 126 patients with hematological malignancies who had 554 febrile episodes were analyzed retrospectively with regard to documented infections and fever of unknown origin. The CRP levels were significantly higher when the blood culture was positive than when it was negative (p = 0.002). The CRP levels were significantly higher when the infection focus was identified than when it was not (p = 0.010). In patients with fever of unknown origin the CRP was significantly lower than in patients with microbiologically documented infections (p < 0.001). Cytotoxic treatment neither reduced nor enhanced the CRP reaction. The serial measurement of CRP is a reliable and readily available means for differentiating between bacterial infections and other causes of fever in patients with hematological malignancies, also during neutropenia and after cytotoxic treatment.


Comparison of the autoSCAN-W/A and Vitek Automicrobic systems for identification and susceptibility testing of bacteria.

The identification and susceptibility testing of bacteria by the autoSCAN-W/A rapid panels and Vitek Automicrobic systems were compared. A total of 291 clinical isolates, including 207 members of the Enterobacteriaceae, 41 nonfermentative gram-negative bacilli, 31 Staphylococcus aureus strains and 12 Enterococcus faecalis strains, were tested. autoSCAN-W/A and Vitek correctly identified 93% and 94% respectively of the Enterobacteriaceae, the identification in an additional 2% and 5% of strains respectively being reported as correct with a low probability. autoSCAN-W/A reported all identification results within 2 h after inoculation, whereas Vitek reported the identification results for the majority of gram-negative bacilli between 4 h and 6 h after inoculation. autoSCAN-W/A and Vitek reported 81% and 74% of MIC results respectively after 3-6 h incubation. The rates of very major susceptibility errors were 0.4% and 0.4% for autoSCAN-W/A and Vitek respectively, the rates of major errors 0.4% and 1% respectively, and the rates of minor errors 4% and 3% respectively. Six of 30 Pseudomonas aeruginosa strains failed to grow sufficiently for susceptibility testing in the autoSCAN-W/A system, and four Xanthomonas maltophilia strains had insufficient growth for susceptibility testing in both systems. The majority of results of susceptibility testing of nonfermentative gram-negative bacilli were reported more than 6 h after inoculation. Both systems were reliable and easy to operate, and gave accurate results for common clinical isolates.


Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus.

In an attempt to identify risk factors for Staphylococcus aureus septicemia, 136 consecutive HIV-infected patients were investigated for the presence of nasopharyngeal colonization with Staphylococcus aureus and subsequent Staphylococcus aureus infection. Sixty of 136 (44.1%) HIV-infected patients had staphylococci which were detected in the nasopharynx on initial culture compared to 12 of 39 (30.8%) patients with chronic diseases and 11 of 47 (23.4%) healthy hospital staff. Another 12 HIV-infected subjects proved to be Staphylococcus aureus carriers on follow-up cultures. Patients with full-blown AIDS had a higher carriage rate compared to subjects who were only HIV-positive (p < 0.05), indicating that Staphylococcus aureus colonized patients were more severely ill. Eight patients with Staphylococcus aureus septicemia were observed, all of whom were carriers; no septicemia occurred in the non-colonized patients (p < 0.01). Colonized patients with neutropenia (< 1000/microliters) were significantly more likely to develop septicemia (p < 0.01). Nasopharyngeal colonization with Staphylococcus aureus and the presence of an indwelling catheter were established to be factors that help identify patients at risk of acquiring subsequent Staphylococcus aureus infection.


Widespread occurrence of multiple drug-resistant Salmonella typhi in India.

Sixteen multiple drug resistant strains of Salmonella typhi belonging to Vi-phage types E1 (14) and O (2) and isolated in Southeast India in 1991 were characterized. All strains were resistant to chloramphenicol and the majority to trimethoprim and ampicillin. In all strains these resistances were encoded by plasmids of the H1 incompatibility group with molecular weights ranging from 110 to 120 megadaltons. Physicians in European countries should be aware that treatment may fail if patients with typhoid fever who have recently returned from the Indian sub-continent are given first-line treatment with chloramphenicol, trimethoprim or ampicillin. With the possible exception of young children, ciprofloxacin is currently the best choice for treatment of such patients.


Current antimicrobial therapy of anaerobic infections.

The treatment of many anaerobic infections involves antimicrobial therapy, appropriate surgical drainage of abscesses, and debridement of devitalized tissue. Most anaerobic infections are polymicrobial and require treatment with agents active against an array of aerobic and anaerobic bacteria. Bacterial resistance, especially to penicillins and tetracyclines, but also to newer agents of other classes, continues to increase. As a result, treatment with more than one drug is often required. Combination therapy is often necessary in serious infection, and is indicated for empiric treatment before receiving culture results. In the past combination therapy has been the mainstay of antimicrobial therapy, but more recent studies suggest that monotherapy for anaerobic infections may dominate the future. Selection of an agent requires consideration of the site of infection and the most likely etiologic agents. In vitro susceptibility is important, but it is not the only determinant of antimicrobial effectiveness. The pharmacology of the drug--absorption, distribution, concentrations in body fluids and tissues, excretion and metabolism--also plays an important role. The nature and severity of the underlying illness are important factors in selecting empiric therapy. Although it is a clinical judgement, in patients considered to have mild to moderate infections, several factors in selecting antimicrobial agents may be considered, including cost, whereas in patients judged to have severe or life-threatening infections, the most potent agents should be chosen as initial therapy, regardless of cost. Finally, the toxicities of the agent must also be considered.


Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine.

The combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul treatment was examined in sublethally and lethally whole-body gamma-irradiated mice. The enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated when a single dose of Ivastimul was administered after irradiation. Ameliorative influence of combined radioprotection may be explained by the haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul.


Distribution of triiodothyronine nuclear receptors during the cell cycle in mouse leukemia cells.

The process of the appearance of thyroid hormone receptors in the cell cycle was studied in mouse leukemia cells L1210. After cell synchronization by 2 mM thymidine for 12 h followed by 80 nM Colcemid for 4 h, the specific binding of triiodothyronine (T3) to its nuclear receptors was determined 3, 6, 9 and 12 h after release from the thymidine-Colcemid block. Three h after release from the block, [125I]T3 specific binding was 11.4 +/- 2.5% of a control value measured for an asynchronous population. An upward slope in progression of T3 nuclear receptors was found 6 h (32.3% +/- 4.5%), 9 h (47.8% +/- 5.2%) and 12 h (83% +/- 4.3%) after release from thymidine-Colcemid block. The data suggest that processes involving T3 receptor promotion in cell nuclei are operative within the late G1 and S phases of the cell cycle, and thus the increase in T3 receptor concentration in the nuclei is in a positive correlation with the number of cells in the S compartment of the cell cycle.


Defective function of blood granulocytes in patients with diabetes mellitus-associated marginal periodontitis.

In ten periodontitis patients suffering from type I diabetes mellitus, phagocytic activity, aggregation and chemiluminescence generation of blood granulocytes were determined. Compared to controls with clinically healthy periodontal conditions, the phagocytosis of zymosan particles and the aggregation response induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine were significantly decreased, whereas aggregation induced by the platelet-activating factor, a potent mediator of inflammation, was significantly enhanced.


[Enzyme deficiency of erythrocytes in human porphyria].

Hereditary enzyme deficiency in porphyrias can be recognized in blood cells. In the red cell four enzymes of heme biosynthesis can be detected: porphobilinogen synthase (delta-aminolevulinic acid dehydrase), uroporphyrinogen synthase, cosynthase, and decarboxylase. A decrease of porphobilinogen synthase is observed in lead intoxication and in a new type of hereditary acute porphyria with nearly total enzyme deficiency in the homozygous state with a residual activity of 1-2% of controls. In another recessive condition, congenital erythropoietic porphyria, the deficient uroporphyrinogen cosynthase shows an activity between 1 and 20%. Acute intermittent porphyria is characterized by diminished uroporphyrinogen synthase which allows the recognition of gene carriers in red cells. In the genetic type of porphyria cutanea tarda triggered by alcohol, oral contraceptives, and liver damage the uroporphyrinogen decarboxylase is decreased to about 50%. In hepatoerythropoietic porphyria, a homozygous variant of porphyria cutanea tarda, decarboxylase activity was found below 10% of controls. With exception of congenital erythropoietic, hepatoerythropoietic porphyria, and lead poisoning enzyme deficiencies of porphyrin metabolism in red cells do not lead to anemia.


[Erythrocyte membrane lipid composition in patient with iron deficiency anemia during treatment].

Red blood cell membrane lipid composition was studied in 51 iron deficiency anemia patients, in 10 of them during ferro-therapy. It was noted that red blood cell membranes contained increased total levels of lipids, phospholipids and significantly decreased levels of cholesterol esters and lysophospholipids. During the treatment, in the presence of a distinct process of the recovery of disturbed lipid composition of red blood cell membranes, a significant increase was recorded in the content of triglycerides, phosphatidyl amines, while phosphatidyl and cardiolipin levels were significantly lowered. Red blood cell membrane lipid content in iron deficiency anemia patients and its dynamics in the process of their treatment might serve as an additional criteria of the body saturation with iron.


[Erythrocyte membrane proteins in patients with hereditary spherocytosis].

Red blood cell membrane proteins were studied in a group of patients with hereditary spherocytosis, in comparison with normal donors, to reveal anomalous proteins associated with this disease. For this purpose red blood cells of the patients and normal donors were fractionated, by the age, in Ficoll-400 gradient, as a result red blood cell membranes were obtained with proteins that were investigated by the method of two-dimensional electrophoresis. In comparison of two-dimensional electrophoregrams of red blood cell membrane proteins of normal donors and those of microspherocytosis patients it was found that the latters had additional peptides in the area of glyceraldehyde-3-phosphate hydrogenase and pyruvate kinase. The changes detected in the red blood cell membrane protein composition might be caused by age shifts in the red blood cell population or by the disease type.


[Organization and results of studies on acute hepatic porphyrias in Poland].

The organization, activities and experience of Porphyria Reference Centre of the Institute of Hematology in Poland is shown. A total of 214 families with acute hepatic porphyria were collected. The family studies in search of latent cases were conducted, and measures for preventing the disease attacks were taken. The therapy of the attacks consisted in glucose and heme arginate infusions, and hyperalimentation in the patients is stressed. The incidence rate of porphyrias in Poland, according to the material collected at the Institute of Hematology is 1:15,000 inhabitants, however, it is suggested that the true value is much higher.


[The results and prospects of research on the hygiene of the industrial microclimate].

The main directions in the research and study of industrial microclimate are represented in the article. Evaluation of the microclimate based on thermophysiology, studies of correlation between the environmental temperature and the human functional status helped to establish the normal parameters, measures of the overheating and the overcooling prophylaxis. New data about the immediate and late effect of single microclimate parameters on the human functional status necessitate the creation of new methodic approaches to the evaluation and control of microclimate conditions.


[The prevention of vibration disease].

Probable cooling of hands must be taken into account in setting up the prophylaxis of pathology due to the local vibration. Warm air pumped into the manual pneumatic devices can eliminate the cooling of operators' hands. The same effect is gained by the physiotherapeutic procedure--the warming and micromassage of hands by the dry air.


[The hygienic assessment of the working conditions and health status of workers on the petroleum tank farms of Bashkiria].

Work conditions and the health status in workers of Bashkirian oil enterprises are characterized. Exposure to oil products composed of alkanes and aromatics, petrol and tetraethyl lead was proved to be the major hazard for workers of all the occupations. Complex of occupational and industrial hazards of Bashkirian oil enterprises harms the health status of workers, which induces the high prevalence of chronic diseases.


[The function of 2 detoxifying body systems in workers of the petrochemical industry].

Studies of the immune status and antipyrine test helped to analyse the status of the two body detoxicants--the immune system and the system of microsomal hepatic oxygenases in petrochemical production workers suffering from the chronic bronchitis and bronchial asthma. Immune deficiency of T and B cells, decreased function of cytochrome P-450 containing monooxygenase system were revealed, which indicates complicated relations between the two body detoxicant systems.


[Human functional status in combined exposure to industrial factors and mining migrations].

The functional status and capacity for work were studied in humans exposed to the combined occupational and natural (everyday mountainous migrations) factors. Occupational factors and vertical migration appeared to effect synergistically on functional systems, which necessitates the further investigations concerning the work normalization in mountainous conditions.


[The basic dynamic indices and structure of morbidity with temporary loss of work capacity in workers of the reactor industry].

Retrospective analysis of morbidity with the transitory disablement in male workers of industrial nuclear reactors during the recent 5 years revealed moderate and low levels of morbidity in causes and days for 100 workers. Respiratory tract diseases, mainly acute, take the first place in the morbidity structure. Parameters were not found depending on age, length of service, total gamma-radiation dose.


[Cellular immunity indices in combined chronic exposure to stress and low concentrations of carbon monoxide (II). Experimental research].

Studies of the chronic combined effects of carbon monoxide low concentrations and psychoemotional stress revealed changes in the peripheral lymphocyte subpopulation in all groups of examinees, connected with the defense activation of the humoral immunity and functional decrease of T lymphocytes. Analysis of correlations of cell subpopulations revealed disorders of their relationships, augmenting with the intensity of exposure. Combined action of carbon monoxide in the maximal of studies concentrations with stress resulted in the most severe changes of nonspecific immunity, which proves decompensated decrease of immunity.


[The epidemiological assessment of the "dose-response" relationship in the hygienic regulation of asbestos-containing dusts].

"Dose-response" dependence worked out by American scientists helped to reveal the linear dependence between carcinogenic risk factor, asbestos containing dust, and lung cancer formation, use it for basing the new MAC for asbestos containing dust taking into account the oncologic security.


[Thermoregulatory characteristics in exposure to high temperature combined with low air humidity].

Sweat evaporation from the skin surface and wearing the loose cotton shirt are proved to diminish the exposure to the high environmental temperature and prevent overheating. Recommendation for prevention of the overheating are suggested.


[The methodological characteristics of calculating the prevented economic loss from disability resulting from occupational diseases in assessing the activities of occupational pathology centers].

Evaluation of prevented economic detriment from the occupational disablement can be used for estimating the economic efficiency of occupational centre activities. Decreased disability pensions as a main item of expenses must be taken into account in evaluation of prevented economic detriment due to the diminished disablement. Regional occupational pathology centre activities aimed at the early diagnosis of complications-free occupational diseases, complete clinical screening, active treatment and control of the adequate employment give a great social and economic effect.


[A method for recording the deep temperature of the human body under cooling and warming microclimatic conditions].

The simple and safe method for the deep body temperature measurement is worked out. The temperature is measured by means of the heat point-sensor and fully corresponds to the deep body temperature. The maximal temperature of the voided urine was measured. The rectal temperature completely coincides with the measured by the stated method in healthy men exposed to high, low and contrast temperatures of air and water.


[The development of occupational hearing loss under the influence of pulsed noise].

The deafness was studied in workers engaged into the weaving and the blacksmithing. Both groups of workers were exposed to the noise dose of 109 dB estimated according to Robinson's formula. Processing of received data in diminished hearing revealed the reliable difference between the studies groups both in quantity of the cochlear neuritis and the grade of the hearing failure. Slight hearing failure predominated in the weavers' group whereas the moderate and severe forms appeared in the blacksmiths. Analysis revealed the positive correlation between the overall noise dose and diminished hearing in all studied groups concerning high and voice frequencies. The impulsive noise appeared to be more aggressive than the constant one.


Interrelations between growth hormone and sex hormones: physiology and therapeutic consequences.

Animal experiments, analysis of growth hormone (GH) secretion in the human, studies on the synergistic metabolic effects between GH and sex hormones using the stable isotope 15N, and long-term growth evaluation of patients with GH and gonadotrophin deficiency treated with testosterone and hGH show that biologically important interrelations exist between GH and sex hormones. They are operative not only at the pituitary and gonadal levels but also in peripheral tissues, where sex hormones modify the metabolic and growth-promoting effects of GH. GH is also important for an optimal androgenic effect of testosterone in development of secondary sexual characteristics. Knowledge of these interrelations is not only of physiological interest, but also of practical clinical value.


Growth as a measure of the nutritional and hygienic status of a population.

The history of the use of children's growth as a measure of the nutrition and hygiene of a population since the early 19th century is outlined. Secular trends towards greater height and earlier maturity are reported; the increase in adult height in British men born between 1900 and 1946 averaged about 1.25 cm/decade and in those born between 1946 and 1960 0.6 cm/decade, according to the data of Kuh et al. [Int J Epidemiol 1991;20:1001-1009]. Social class differences in height persist in the UK, amounting to almost 2 cm between the well off and the unskilled. The average height of subgroups of most populations serves well as a proxy for their health status and relates to their mortality rate.


Growth hormone and ovulation: is there an indication for treatment of infertile women with growth hormone?

We have explored the use of growth hormone (GH) for ovulation induction and ovarian stimulation for in vitro fertilization and embryo transfer (IVF-ET). We first compared the effects of co-treatment with GH and placebo on the dose of gonadotrophins required to induce ovulation. The patients were gonadotrophin deficient and, for the main part, hypopituitary. We found a significant reduction in the dose of gonadotrophins and the duration of treatment needed to induce ovulation. The dose of GH used in these studies was substantial, and we await the results of a multi-centre trial attempting to establish a dose-response relationship. We then explored the role of GH in patients undergoing IVF-ET. The end-point measured was an increase in the number of follicles developing during standard treatment with gonadotrophins. In the first randomized controlled clinical trial we found a suggestion only of an enhanced ovarian response to co-treatment with GH. Specifically selected patients with ultrasound-diagnosed polycystic ovaries were then treated. All were receiving treatment with luteinizing hormone-releasing hormone analogue as part of their ovarian stimulation protocol. The results showed clearly that in this group of patients, co-treatment with GH augmented the ovarian response to treatment with gonadotrophins. We also found an increase in serum and follicular-fluid insulin-like growth factor I (IGF-I) concentrations, but since the serum concentrations always exceeded those in follicular fluid, the results were consistent with the notion that follicular-fluid growth factor was predominantly derived from serum IGF-I rather than being synthesized locally.


The role of growth hormone and insulin-like growth factor I in the regulation of male reproductive function.

Animal experiments and clinical studies on the interactions between growth hormone (GH) and the male hypothalamic-pituitary-gonadal axis have predominantly concentrated on GH and sex steroid interactions in the regulation of growth and development, or on the metabolic effects of GH. In contrast, little attention has been paid to the possible effects of GH on spermatogenesis, although the first report dealing with this topic was published almost 30 years ago. The interactions of GH and its main mediator, insulin-like growth factor I (IGF-I), with the hypothalamic-pituitary-gonadal axis, and their role in spermatogenesis have recently been investigated using in vitro systems and different animal models (mice and rats). Using Leydig and Sertoli cell cultures, complex interactions between GH/IGF-I and the gonadotropins affecting differentiated cell functions, e.g. steroidogenesis and cell division, have been demonstrated at the cellular level. In vivo studies using immature and mature hypophysectomized rats and GH-deficient mutant male mice and rats indicate that IGF-I can play an important role in the regulation of steroidogenesis and spermatogenesis. Furthermore, although follicle-stimulating hormone and luteinizing hormone are the major regulators of testicular IGF-I production, GH may play an indirect role by potentiating the actions of the gonadotropins in regulating testicular IGF-I content. A large proportion of men presenting at male-infertility clinics are diagnosed as having idiopathic infertility. Further studies are necessary to investigate whether defects associated with GH and/or IGF-I effects in the testis are the cause of male infertility in a small group of these patients.


What is the role of growth hormone and related peptides in implantation and the development of the embryo and fetus.

The role of growth hormone (GH) and the related placental lactogens in implantation and subsequent embryonic and fetal development is an enigma. Firstly, these peptides are abundant in both the fetal and maternal circulation. The variant growth hormone (hGH-V) is expressed by the placental syncytiotrophoblast and is released into the maternal circulation. It is not detectable in fetal blood. Fetal pituitary (GH) is abundant but is not a primary stimulus to human fetal musculoskeletal growth, since hypopituitary newborn infants have near-normal birth size. However, pituitary hGH has been shown to stimulate pancreatic islet growth and insulin release in vitro, and to be a mitogen for fetal hepatocytes obtained in late first trimester. This selectivity of action is confirmed by the immunohistochemical localization of hGH receptor in the human fetal kidney, endocrine pancreas, liver, skin and brain during the first and second trimester, and their absence from the musculoskeletal system, gut and lung. High-affinity human placental lactogen (hPL) receptors are abundant in animal and human fetal tissues, and hPL can attain concentrations of 10 nM in the human fetal circulation. In vitro data strongly suggest anabolic and mitogenic actions for PL on fetal tissues, including amino acid transport, hepatic glycogenesis, protein synthesis, and stimulation of insulin-like growth factor and insulin release. The PL axis in the fetus is influenced by maternal nutrition. Despite these findings, definitive evidence is still lacking that PL contributes to fetal growth and development in utero.


Epidemiologic survey of patients treated with growth hormone in France in the period 1959-1990: preliminary results.

Because the delivery of growth hormone (GH) was centralized from 1977 in France, it has been possible to conduct, during the second half of 1990, a nationwide survey of the health status of patients treated with GH from the year 1959. A questionnaire regarding the 5,546 patients recorded for the period 1959-1990 was sent to the prescribers or the patients. 5,418 more or less completely documented reports were obtained. The mean age of the patients at the onset of GH treatment was 11.0 +/- 4.1 years. 1,937 of them had at this time some important disease associated with GH deficiency. The mean duration of treatment was 3.99 +/- 3.05 years. 3,446 patients were still under follow-up. Very recent information (1990-1991) was given for 82.7% of patients, less recent data (1985-1989) for 13.4%. For 3.9%, no data beyond 1985 were obtained. 77 patients had died, 38 from neoplastic disease (mainly recurrence of a primary malignancy), 10 from accident, 3 by suicide, 7 with neurological disease [only 1 case of Creutzfeldt-Jakob disease (CJD) was reported at the time of the survey], the others from various causes. No abnormal frequency of posttreatment leukemia, lymphoma, malignancies, hip diseases, glucose intolerance or other disease focusing attention, was found in the survey. From the time when this survey was completed (December 1990) to that of this report (May 1992), other cases of CJD have been reported in France: 3 ascertained, 7 clinically resembling but not yet certain. These 10 patients were treated for complete GH deficiency, 6 of congenital or neonatal cause and 4 after neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)


Untoward events in patients treated with growth hormone in the USA.

Since 1960 more than 30,000 children have been treated with growth hormone (GH) in the USA. Ten cases of Creutzfeldt-Jakob disease have been associated with the use of GH purified from pituitaries in the USA, and more cases may appear in the future. Ten cases of leukemia or preleukemia have been reported in patients undergoing GH treatment in the US. Eight of these patients had previously diagnosed tumors of the central nervous system. As the indications for GH treatment broaden, and the dosages of GH increase, more unfavorable clinical events linked directly to the biological actions of GH can be expected to occur. Continued surveillance for clinically important GH-associated events is important.


Tumour occurrence and recurrence.

There is growing concern about the oncogenic potential of growth hormone (GH) used therapeutically. In rat experiments, a variety of malignant tumours have been induced following administration of supraphysiological doses of GH, whilst in other studies in hypophysectomized animals a lower than normal incidence of carcinogen-induced neoplasms was reported. In acromegaly, in which there is a pathologically sustained high GH level, there is a significantly increased incidence of cancer in general and specifically of colonic neoplasia. To determine whether the use of GH in the treatment of radiation-induced GH deficiency causes tumour recurrence, a comparison was made of tumour recurrence rates between 47 children treated with GH for radiation-induced GH deficiency after treatment for a brain tumour and a control population from the North West Children's Cancer Registry who did not receive GH (n = 160). All cases of acute lymphoblastic leukaemia (ALL), including those that were (n = 15) and were not (n = 146) treated with GH were reviewed. The computerized tomography (CT) scans in the children with brain tumours were reviewed at the time of GH commencement and subsequently. There were 5 brain tumour recurrences after GH therapy: 1 astrocytoma, 2 ependymomas and 2 medulloblastomas. Adjusting for variables other than GH which might affect tumour recurrence, the estimated relative risk of tumour recurrence was 0.82 (95% confidence interval: 0.28-2.37). In each tumour category there was no association between the use of GH and subsequent tumour recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)


Leukemia in growth-hormone-treated patients: an update, 1992.

Since 1988 the number of growth hormone (GH)-treated patients has markedly increased worldwide. To date, leukemia has been observed in 31 patients during or following GH therapy and related malignancies in 2 further patients. Leukemia occurred in 10 patients in Japan, 10 in the USA, and 10 in Europe, and in 1 patient in Canada. In 29 patients GH therapy had been started in 1975 or later. The onset of leukemia was 1984 or later in 28 patients with a mean time between the start of GH therapy and leukemia onset of 5.0 (0.2-18.8) years. Patients had received both pituitary and recombinant GH in moderate doses. In 15 patients definite additional leukemia risk was evident: Fanconi anemia in 2, myelodysplastic syndrome in 1, Bloom's syndrome in 1, radiation for brain tumor (+chemotherapy) in 9, chemotherapy in 2. The leukemic patients without a strong additional risk do not represent a definitely higher leukemia incidence worldwide, except for Japan where the occurrence is higher than expected.


Thyroid function during growth hormone therapy.

Administration of growth hormone (GH) in GH-deficient patients has been reported to cause a variety of perturbations in thyroid function. Reports range from decreased sensitivity of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation and induction of hypothyroidism to increased energy expenditure and enhanced peripheral thyroxine (T4) to triiodothyronine (T3) conversion. Some of the diversities may relate to the fact that earlier studies were uncontrolled case reports, which furthermore employed pituitary GH preparations, which may have been contaminated with TSH. A confounding variable in terms of incipient TSH insufficiency in some patients may also have been present. Data from a placebo-controlled crossover study of 4-months GH therapy in GH-deficient adults, some of whom were on ongoing T4 substitution, revealed that the most prominent effect on thyroid function was increased peripheral T4 to T3 conversion without significantly affecting TSH levels or secretion from the thyroid gland. It was furthermore observed that T3 levels during placebo were significantly decreased compared to an untreated healthy control group. Comparable findings have been made in a controlled study of 6-months GH therapy in adult-onset GH-deficient patients. More recent data suggest that these effects prevail after long-term (16 months) therapy. Similar findings have also been reported in healthy subjects receiving pharmacological GH doses. It is likely that this effect is not caused by GH per se inasmuch as reduced T4 to T3 conversion is a common observation in catabolic states with concomitant GH hypersecretion. It remains to be shown whether insulin-like growth factor I (IGF-I) stimulates peripheral deiodination.


Metabolic changes and vascular risk factors in hypopituitarism.

Adults with hypopituitarism die prematurely, and the excess mortality is from vascular disease. On echocardiography we have demonstrated abnormalities of myocardial diastolic function in hypopituitary adults, indicating possible early ischaemic change. Peripheral arterial disease is evident on ultrasonography. Vascular risk factors have also been examined. Impaired glucose tolerance and unrecognized diabetes are common in hypopituitary adults. Total cholesterol levels are elevated, particularly in hypopituitary women. The role of growth hormone (GH) deficiency in the vascular disease and in the vascular-risk-factor abnormalities is unknown at present. Prolonged GH therapy causes a decrease in the levels of fasting total cholesterol, without any adverse effects on glucose homeostasis. GH therapy trials in adults will clarify the role of GH in the excess vascular risk of hypopituitarism. Prolonged GH therapy will be necessary for the vascular effects to be defined.


Human growth hormone but not insulin-like growth factor I positively affects whole-body estimates of protein metabolism.

Human growth hormone (rhGH) increases estimates of whole-body protein synthesis, but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In addition, rhGH stimulates protein synthesis in skeletal muscle tissue. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. Using high-dose prednisone as a controlled model for protein catabolism in normal volunteers, high-dose rhGH together with prednisone prevents the protein catabolic effects of prednisone alone. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole body proteolysis, suggestive of a predominant insulin-like effect. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. Thus, the mechanism of action of rhGH on body protein metabolism remains to be elucidated. However, rhGH alone or in combination with rhIGF-I may provide a new management strategy in a variety of protein catabolic conditions in humans.


Malnutrition in Crohn's disease: substrate deficiency or misuse?

Growth failure is frequently associated with Crohn's disease. However, it does not seem to be fully accounted for by overt endocrinological abnormalities or nutrient deficiencies. It may be related to an abnormal utilization of available substrates, particularly proteins, due to an imbalance in protein metabolism kinetics. Its primary mechanism may be an increase in protein breakdown rates over synthesis, specifically related to the associated inflammatory syndrome, and progressively leading to a protein debt. Reduction in food intake would only exaggerate this trend by further reducing the synthesis to breakdown ratio, whereas nutrient supplementation merely compensates for the deficit by promoting protein synthesis.


Growth hormone and nutrition.

The regulation of growth hormone (GH) secretion in humans is a complex process which comprises more than stimulation by GH-releasing hormone and suppression by somatostatin. Although these two hypothalamic hormones are the primary regulators of GH secretion, they most likely function as the final pathway through which numerous factors influence GH synthesis and secretion. Some of the modulators of GH secretion include neurotransmitters, circulating glucose, insulin-like growth factor I and gonadal steroid concentrations. Age, nutrition and body composition are also related to the amount and pattern of GH secretion in humans. The influence of nutritional status on GH secretion is becoming more clearly defined.


Nutrition and the secular trend of growth.

Japan has been experiencing ever more rapid socioeconomic development and changes in eating habit, especially in children, since the end of the Second World War. These occurrences (westernized life style) have greatly affected the growth of Japanese. Nutrition is the most important factor in promoting the physical growth in childhood during food supply shortage, and for a relatively short term the secular trend in linear growth will reach a plateau if the food supply is adequate, but the secular trend is also limited. Since the condition for this limitation should be comprised by genetic factors, we are most interested in investigating and analyzing these genetic factors in the near future. Overeating adversely affects growth in childhood, with most common representatives of these ill effects being atherogenic risk factors such as obesity, hypertension and hypercholesterolaemia.


The effects of growth hormone therapy on spontaneous sexual development.

We have carried out a prospective randomised study in 52 (46 male, 6 female) children with isolated growth hormone (GH) deficiency treated with a GH regimen of 15 IU/m2/week administered as a daily subcutaneous injection. At the onset of the pubertal growth spurt, the patients were randomised to receive either an unaltered regimen (26 males, 1 female) or 30 IU/m2/week (20 males, 5 females). There was no change in the frequency of GH administration. The number of females in this study was too small to give a meaningful result. In contrast, the boys treated with either dose regimen showed no significant alteration in growth rate, but there was a faster than normal progression in pubertal maturation. It is concluded that the optimum final height of children with isolated GH deficiency may not be achieved in patients without the therapeutic manipulation of the onset and/or duration of puberty. 16 short normal children (9 males, 7 females) were treated with GH in a regimen of 25 IU/m2/week (range: 20-30) as a daily subcutaneous injection. The mean age for the onset of GH treatment was 11.5 and 11.0 years in the boys and girls, respectively. Our data suggest that both boys and girls had a more rapid rate of pubertal maturation than normal. It may be that in terms of final height prognosis, the events of puberty related to GH treatment counterbalance the improvement in growth prognosis during prepuberty.


Effects of changes in nutritional conditions on timing of puberty: clinical evidence from adopted children and experimental studies in the male rat.

Among 32 patients with idiopathic central precocious puberty seen during a 3-year period, 1/4 were adopted children from developing countries who showed early sexual maturation during the catch-up process following their arrival in Belgium. To study the possible mechanism accounting for such clinical observations, we used the male rat as a model, and evaluated the effect of variations in early nutritional conditions, by manipulating litter size, on hypothalamic and testicular maturation. We had shown previously that, in the male rat, onset of puberty was preceded, between 15 and 25 days of age, by a transiently increased activation of N-methyl-D-aspartate receptors involved in a facilitatory control of pulsatile secretion of gonadotropin-releasing hormone. We also showed that the proportion of elongated spermatids in testicular cell homogenates increased between 25 and 45 days of age. When compared to pups of a small litter (6/dam), those of a large litter (14/dam) showed a reduced growth rate (1.9 vs. 3.5 g/day) before weaning (21 days), whereas they grew at a similar rate (5.6 vs. 4.7 g/day) after weaning. At 35 days of age, the animals raised in the large litter showed evidence of delayed hypothalamic and testicular maturation when compared to animals from the small litter. Reduction of litter size at 17 days allowed food-restricted pups of a large litter to resume a normal growth rate before weaning.(ABSTRACT TRUNCATED AT 250 WORDS)


Perioperative nursing: a special nursing specialty.

The intraoperative phase of perioperative nursing practice is a special specialty, as it combines the nursing model and the collaborative model for specialization. As a nursing model, it focuses on the behavioral sciences, education, and nursing as a caring science. As a collaborative model, it requires skilled care with an additional knowledge base acquired from medicine and the behavioral and biological sciences. The nature of the operating room may distort the image, because although nurses work closely with other health care team members in diagnosing and treating patients, in this special specialty the scope of practice is uniquely nursing.


[Social inequalities in health in the city of Málaga].

Social inequalities and health inequalities are closely related, and their reduction is the goal of international organizations and governments as well. In order to better understand the territorial distribution of social inequalities in the city of Málaga (Spain) and compare them with measured health differences, a descriptive study was done using different sources of information. Using the city's neighbourhoods as the unit of analysis, a cluster analysis was carried out based on a set of demographic, socioeconomic and standard of living indicators. This led to the configuration of six social areas within the city. In these areas, as defined by socially homogeneous criteria, diverse health indicators have been measured, leading the verification of important health differences among them. For example, clear differences in mortality rates between Area IV (socioeconomically deprived) and Area III (with a higher standard of living) are observed: the ratio between their respective "years of potential life lost" was 1.79, and between standardized mortality rates, 1.42. A similar disadvantage in low birth weight was confirmed notably so in adolescent pregnancies (five times higher). In conclusion, those areas of the city with a lower socio-economic status also had the lowest health levels.


[The association between iron deficiency and learning disorders in preschoolers].

With the aim preventing future problems of underachievement at school, we studied the possible relationship between learning difficulties and iron deficiency in nursery-school children. To do this, we determined the prevalence of iron deficiency and the prevalence or learning difficulties in the different areas of mental development in a sample of 136 nursery school children coming from the Alaquàs public school (Valencia), aged between four and five years. Their nutritional state and ferric state, socioeconomic and cultural level, and psychomotor development were evaluated. All the children were in a good nutritional state, coming from homogeneous families as regards their socio-cultural level and being divided into two groups as regards their economic situation. The iron deficiency prevalence was 17.6% in stage I (ferritina sérica < 12 ng/l) and 22.8% in stage III (anemia ferropénica). The coefficient for overall development was 85.95, the lowest marks being in the speech area. A positive association (prevalence ratio = 2; IC 95% = 1.1-8.3) between iron deficiency in its III stage and changes in the specific area of analysis and synthesis.


[The demand for care and systems of access in primary health care].

The aim of the investigation was to assess variations in the demand for medical care in the primary care centre of Ciudad Badia (Barcelona, Spain). The records of attendance were analysed over a period of seven years. During this period, some changes were made which affected the way the centre was used by patients, such as the creation of systems which required notice of medical and nursing appointments, the reduction of spontaneous attendance, and the introduction of a card for medication for the chronically sick. These changes were accompanied initially by a decrease, then a stabilisation, and afterwards a slight increase in total number of visits. All visits (with notice) rose from 5.3% in 1983 to 45.2% in 1989. Similarly, nursing visits (with notice) increased from 4% to 9.5 of total activity. Emergency visits in the same period rose from 3.4% to 8%. It is concluded that changes that were introduced raised the level of commitment of the staff to medical work-both preventive and therapeutic, as well as the improvement of the organisation of attendance at the centre and a higher satisfaction of users of the centre and the medical staff.


[The reasons for consultation and active problems. A key for the understanding of information in primary care].

The aim of this work is to assess the major differences found in the information content of the registers in primary care according to whether the registration includes the Reason (s) For Encounter (as ascertained by the professional) or the Active Health Problem (s). The information used is based on an observational study of a representative sample of the consultations to eight general practitioners from the Principate of Andorra. The study was performed during the period of May-June 1989. 547 consultations are analysed. A better specificity and information content is observed when both approaches are registered. Active Health Problems seem to be barely related to Reasons for Encounter and it seems that they could have as much, if no more. Influence in the process of care, than the RFEs it selves.


[Advertising, advertising legislation and health].

The media and specifically magazines and sunday supplements contain advertisements, some of which can be dangerous to one's health. We have investigated these types of advertisements, which were included in the 15 top sales magazines in Spain. The period of analysis corresponded to the period april-may, 1991. We have compared the results obtained with the results of a previous investigation carried our in 1987, using an identical method. We have tried to test if the so-called Law of Publicity of 1988 has had any effect on publicity. We have found, 1383 advertisements that could have a damaging effect on one's health. Although the total number of advertisements have decreased over this four year period, the law has hardly produced any influence on publicity, and we have found breaking of the law in the investigated material.


Dairy breed bull with complex chromosome translocation: fertility and linkage studies.

A chromosome study was performed on the offspring of an American Brown Swiss bull, which was carrier of a complex chromosome translocation. A total of 10 phenotypically normal calves were examined and a similar complex translocation was detected in five calves. The translocation involved identifiable parts of chromosome number one and eight. Furthermore, the terminal band of chromosome one had been translocated to an unidentified chromosome. One of the calves also carried a 1/29 centric fusion chromosome. Pedigree and chromosome analysis showed that the centric fusion originated from another American Brown Swiss bull. A linkage study was performed and an indication of linkage between the Z blood group system and the complex translocation was found. The fertility of the bull was studied, and it was found to have a severely reduced fertility mainly due to an increased rate of early embryonic mortality.


Sex chromosome abnormalities in natural populations of the common vole (Microtus arvalis).

Four specimens with an aberrant sex chromosome constitution were found in natural populations of the common vole (Microtus arvalis). Two females had an X0 sex chromosome constitution and single males were 2n = 47, XXY and 2n = 47, XYY, respectively. No apparent phenotypical anomalies were recorded in the sex chromosome aneuploids, but their fertility may have been impaired. The incidence of sex chromosome aneuploidy seems to be unusually high in natural populations of the common vole (1.5% of animals examined). Possible explanations for this are discussed.


[The possibilities for the participation of local corporations in the management of health services].

Strategies that stimulate the involvement of the community in the National Health System would provide more important role for the city councils in the management and control of public health care. This has currently proven to be difficult due to a new centralism at the Autonomous Community level. In this paper, recent collaborative experiences between municipalities and the National Health System are reviewed. Also, different ways for stimulating a real involvement of city councils in the health care are suggested: from managing new facilities and controlling existing facilities at the primary health care level, to a deep, not merely administrative, inclusion of the local health services into the National Health System.


An intriguing Y chromosome in Heteromys anomalus (Rodentia, Heteromyidae).

The mitotic chromosomes of the pocket mouse Heteromys anomalus (Rodentia, Heteromyidae) from Venezuela were analyzed by means of conventional staining and various banding techniques. The karyotype of this species is distinguished by a Y chromosome with exceptional banding properties. The very large heterochromatic Y long arm shows a remarkable bright quinacrine fluorescence, but only moderate or dull fluorescence when labeled with other AT base pair-specific fluorochromes. The implications of these findings are discussed.


No adaptive response of Chinese hamster ovary cells to low doses of ionizing radiation.

Chinese hamster ovary (CHO) cells that had been exposed to very low doses of ionizing radiation from incorporated tritiated thymidine or X-rays were shown not to be more resistant to the induction of chromatid aberrations by a subsequent higher dose of ionizing radiation than previously untreated cells. The adaptive response to ionizing radiation was absent both in cells challenged with high doses of X-rays (1.25 Gy) and in cells post-treated with thermal neutrons (0.5-1 x 10(12) n/cm2). In agreement with these observations in CHO cells we were unable to demonstrate an adaptive response to X-rays also in human lymphocytes from five different donors.


A comparison of light intensity preferences for an oviposition site in parthenogenetic and bisexual strains of Drosophila.

On the assumption that the survival of a parthenogenetic strain in nature relies on the strain's ability to compete with the bisexual population, we attempted to discern any diminution of competition between bisexual strains of Drosophila and parthenogenetic strains derived from them on the basis of light intensity preferences in choosing an oviposition site. Four different experiential conditions were imposed on each strain prior to testing for light intensity preferences for an oviposition site. Most light responses are significantly different in each strain for the four experiences. There are also significant differences among the bisexual, unisexual and F1 females of a given strain and between strains. Further experiments were performed to determine light preferences during oviposition when unisexual and bisexual females were in direct competition. In only one comparison were their light preferences significantly different. All strains were unique in their overall behavioral spectra.


Chromosomal localization of the hormone sensitive lipase (LIPE) and insulin receptor (INSR) genes in pigs.

Using rat hormone sensitive lipase (LIPE) and human insulin receptor (INSR) cDNA probes, the LIPE gene was assigned to chromosome 6p11-q21 and the INSR gene to chromosome 2q11-q21 in pigs by in situ hybridization. In humans, these two genes are located on the q and p arms of chromosome 19, respectively. The present results provide the first in situ hybridization mapping data for porcine chromosome 2.


Assignment of the bovine immunoglobulin gamma heavy chain (IGHG) gene to chromosome 21q24 by in situ hybridization.

By the use of in situ hybridization, the bovine immunoglobulin gamma heavy chain (IGHG) gene was assigned to chromosome 21q24. Fifteen percent of the total grains were scored on chromosome 21, with about 65 percent of these grains located on the q24 band. The present results confirm a previous synteny study and provide the precise chromosomal localization of this gene in the cattle genome.


A difference in the proteins found in young adults of inbred strains of Drosophila melanogaster which correlates with genetically-determined, long or short life span.

One-dimensional electrophoresis was performed on extracts of flies collected from across all ages. Protein gel patterns were compared for two strains of Drosophila melanogaster with distinctly long and short adult life spans that result from different alleles of longevity genes. An inter-strain difference was observed in the changes in protein pattern in the 77 kDa region in period of day 0-5 after emerging. We propose that the protein involved is a product of autosomal longevity alleles A1 and A2 at the Jm A locus and is related to development of longevity potentials in the preimaginal stage.


Purification and characterization of a protein associated with genetically-determined longevity difference in Drosophila melanogaster.

Earlier studies have shown a correlation between the presence of a 77 kDa protein in the proteins extracted from young adult Drosophila melanogaster (D.m.) and the autosomal longevity allele. A2 at the JmA locus. In this study, a 77 kDa protein has been isolated from pupae of D.m. of a long-lived strain of genotype A2A2, and was purified by DEAE chromatography, ConA column chromatography, and two cycles of gel filtration. The purified protein has a molecular weight of 76,600 (by SDS-PAGE), an isoelectric point of pH 6.5, and molar extinction coefficient A(280(1%) = 18.3. It is a glycoprotein containing 3.3% hexose. Supplementing the food of D.m. with the purified protein at 5 x 10(-4) micrograms/ml, beginning at day 5 after emergence, resulted in an increase in the survival rate and maximal life span of both short-lived and long-lived strains of D.m.


High frequency of telomeric associations and chromatid exchanges and breaks in human ovarian carcinoma.

Cytogenetic analysis of an unselected series of twenty human serous adenocarcinomas and undifferentiated carcinomas of the ovary revealed the presence of telomeric associations (tas) and unstable chromosomal aberrations, including chromatid-type exchanges (cte) and breaks (ctb) in high proportion of tumors studied. Tas and cte & ctb were present in 75% and 55% of tumors, respectively. Involvement of different chromosome telomeres in tas seemed to be random. This is the first report describing telomeric associations in ovarian cancer. Our findings suggest that the frequency of extensive spontaneous chromosome breakage in ovarian carcinoma may be higher than that reported in the literature.


Genetic basis of reduced eyes in the hybrids of Drosophila virilis phylad species.

Structural anomalies were detected in F1 and backcross hybrids of Drosophila virilis and three of its sibling species Drosophila novamexicana, Drosophila americana texana and Drosophila americana americana. Similar but not identical anomalies have been described in D. virilis x D. lummei hybrids. F1 (D. virilis x D. novamexicana) hybrids had only slight disorders in the abdominal cuticula, but 5.3% of the first backcross generation hybrids had reduced eyes. Eye defects in the second generation were due to interaction of the heterozygous fourth chromosome of D. novamexicana with the homozygous D. virilis chromosomes 2 and 3. Reciprocal F1 hybrids between D. virilis and D. a. americana and between D. virilis and D. a. texana had normal eyes, but in the second hybrid generation 4.9% of D. virilis x D. a. americana and 1.6% of D. virilis x D. a. texana hybrids had anomalous eyes. In D. virilis x D. a. texana hybrids, the heterozygous fourth chromosome of D. a. texana was incompatible with homozygous D. virilis chromosomes 2 and 3. Of the D. virilis x D. a. americana hybrids homozygous for D. virilis chromosomes 2 and 3, 10.2% had the eye defect. The incompatibility system of non-conspecific chromosomes causing the eye anomalies in the hybrids of these three species pairs was different from those in D. virilis x D. lummei hybrids and has evolved independently after the diverging of the American lineage from D. lummei.


Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera.

The sclera, the outermost sheath of the optic nerve and the dura mater have been investigated histologically and ultrastructurally. Although these tissues appear very similar under the light microscope, being dense connective tissues mainly composed of collagen bundles and a limited amount of cells and elastic fibres, they exhibit subtle differences on electron microscopy. In the dura and sclera collagen appears in the form of large, nonuniform fibrils, similar to those commonly found in tendons, while in the optic nerve sheath the fibrils appear smaller and uniform, similar to those commonly observed in reticular tissues, vessel walls and skin. Freeze-fracture also reveals these fibrils to have different subfibrillar architectures, straight or helical, which correspond to 2 distinct forms of collagen fibril previously described (Raspanti et al. 1989). The other extracellular matrix components also vary with the particular collagen fibril structure. Despite their common embryological derivation, the dura mater, optic nerve sheath and sclera exhibit diversification of their extracellular matrix consistent with the mechanical loads to which these tissues are subjected. Our observations indicate that the outermost sheath of the optic nerve resembles the epineurium of peripheral nerves rather than the dura to which it is commonly likened.


A morphometric study of histological variations during cellular differentiation of normal human colorectal epithelium.

Quantifiable variations existing in the colorectal crypt during cellular differentiation were detected by using simple computer-aided morphometric techniques applied to routinely prepared H&E stained and semithin toluidine blue stained sections of normal colonic mucosa. Generally, most of the morphometric parameters including nuclear volume, nuclear volume weighted mean volume, cytoplasmic volume, cellular volume, nuclear axial ratio (a/b), mean nuclear diameter, nuclear shape factor (NSF) and nuclear maximum angle (Agmax) showed an increasing trend between basal and surface segments. Conversely, the nuclear-cytoplasmic (N/C) ratio, NSF and nuclear circularity index (NCI) decreased between these segments. Epithelial cells in the basal segment had the highest N/C ratio and the lowest cell volume due to their low volumes of cytoplasm. However, substantial increases of cytoplasmic volume occurred in the intermediate segment, thereby expanding the cell volume to 136% of that of the basal segment cell. Data for a/b, NSF, NCI and Agmax suggest that the epithelial nuclei were more ellipsoidal in shape and were aligned more perpendicular to the basement membrane as they reached the surface epithelium. Numerical densities for epithelial cell nuclei were highest in the basal segment, indicating more nuclear profiles at this region per unit area or volume. This also suggested that the basal segment was the active proliferating zone. Such observations agree with previously reported cell kinetic and autoradiographic studies.


A fractionator study of the effects of undernutrition during early life on rat Purkinje cell numbers (with a caveat on the use of nucleoli as counting units).

The effects of varying periods of general protein-calorie undernutrition during early life on Purkinje cells in the cerebellum of the rat were examined. In Experiment 1, animals were undernourished from d 18 of gestation until either d 30 or d 60 of postnatal age, followed in some cases by a period of nutritional rehabilitation. In Experiment 2, rats were undernourished from conception until d 30 postnatally, followed by a period of rehabilitation until 60 d of age. The 'fractionator' method was employed to estimate the total number of cerebellar Purkinje cell nucleoli. If each cell has one nucleolus, this number is equal to the number of Purkinje cells. In Experiment 1, the estimated mean number of Purkinje cell nucleoli varied between 188,000 and 273,000 for the groups of animals studied. However, the interanimal variation was large and 2-way analysis of variance tests failed to reveal any statistically significant age, nutrition or interaction effects. In Experiment 2, rats killed immediately after the period of undernutrition possessed significantly fewer Purkinje cell nucleoli than age-matched controls. This did not represent a real decrease in cell number. Instead, the result could be explained by a change of Purkinje cell morphology in undernourished rats. The change included nucleolar regression. Nutritionally rehabilitated animals had similar numbers of nucleoli to control rats. It is concluded that the levels and periods of undernutrition used in these experiments did not affect significantly the total numbers of cerebellar Purkinje neurons.


Lymph pathways associated with Peyer's patches in sheep.

Lymphatic drainage of the ileum associated with Peyer's patches begins with lymph entering a single lacteal of the villus, probably through intercellular flaps, which prevent retrograde flow to the interstitium. These lacteals are continuous with an interconnecting plexus of branching sinuses which surrounds the crypts and follicle domes in the lamina propria. Small vessels emanating from this plexus penetrate the muscularis mucosa, where lymph can either flow within septal vessels to the deep submucosa, or enter the follicular sinuses to move freely around follicles, and through gaps in septal walls. All lymph enters a deep submucosal network where retrograde flow is prevented by valves. Lymph is then conveyed through vessels passing between the fibres of the muscularis externa to other lymphatics, which transport lymph from the ileal surface to the mesenteric nodes.


Modification of lectin binding in rat gut mucosa during experimental cholestasis.

Glycoconjugate distribution on rat gut mucosa has been studied by using peroxidase-labelled lectins (Lotus tetragonolobus, Dolichos biflorus, Arachis hypogaea and Glycine max) after surgical interruption of the common bile duct. Specimens from cholestatic rats were compared with sham-operated (simple laparotomy) and normal controls to determine which of the observed modifications could be due either to the operation itself or to the cholestasis. Most of the modifications occurred in the duodenum. The operation itself modified some binding properties. Lotus tetragonolobus binding extended both in cholestatic and in sham-operated rats, but returned to normal levels earlier in sham-operated than in cholestatic rats. Conversely, cholestasis induced (1) almost total loss of Arachis hypogaea binding in the Golgi zone of superficial duodenal goblet cells; (2) an increase at the 14th postoperative day of Dolichos biflorus binding in the cytoplasmic calyx of goblet cells which then diminished up until the 28th day; and (3) an increase of Glycine max binding in the Golgi zone of goblet cells.


The intraglandular submandibular ganglion of postnatal and adult rats. II. A morphometric and quantitative study.

A morphometric study was undertaken on the submandibular ganglion cells in rats of different ages. This showed a direct proportional increase with age in all the variables measured. Mean cross-sectional cell area showed the most dramatic growth, an increase of more than 5-fold between birth and young adulthood. Mean cell diameter and cell perimeter doubled over the same period. The growth of the nucleus, expressed as diameter, was slower when compared with that of the ganglion cells as a whole. The number of intraglandular ganglion cells remained relatively unchanged from birth to young adulthood, ranging from about 3000 to 5000 cells. They were mainly distributed at the hilar region of the submandibular salivary gland, contributing 1/2 to 2/3 of the total ganglion cell population. The second largest cell population was in the intralobular region, which made up about one-third of the population. The least populated region was in the connective tissue of the sublingual salivary gland, which contained only about 5-7% of the total cell number. Cell counts based on the fluorogold labelling method were generally lower than those made after haematoxylin and eosin staining. In the 2-d-old animals, counts of fluorogold-labelled cells were only about half the H & E counts. The discrepancy may be due to the thicker sections used in the fluorogold method, superimposition of cells leading to an underestimation of cell numbers. Nevertheless, the fluorogold labelling method provided rapid and reproducible results. Its main advantage is that the labelled ganglion cells emit a bright yellow fluorescence which is readily identified; the other is the simplicity of the procedure, as labelling of ganglion cells can be achieved by the intraperitoneal route.


Growth of the ribs at the costochondral junction in the rat.

The in situ growth of the ribs at the costochondral junction was examined by 2 methods. In the first, 3 threads were tied around the 5th, 6th or 7th ribs of 20-d-old rats. The first thread was located around the bony part of the rib close to the costochondral junction, the second around the cartilaginous part the same distance away from the junction, and the third also around the cartilaginous part but further away. The distances between the threads were measured at 20 and 40 d and were found to have increased considerably. In the second part, an immunohistochemical method using bromodeoxyuridine was employed to detect proliferating cells at the costochondral junction. The most active cell proliferation was observed in the proliferative zone, but mitoses were also noticed in the germinative zone. The results provide further evidence that the growth potential of costochondral grafts used in reconstructive surgery is related to the length of their cartilaginous portion.


Elucidation of aspects of murine skeletal muscle regeneration using local and whole body irradiation.

To investigate the role of proliferating local and emigrating circulatory leucocytes in skeletal muscle regeneration in mice, their bone marrow was ablated with whole body irradiation and compared with the effects of local irradiation. The results indicate that (1) the sealing of damaged myofibres is a function of local cells and is not dependent on the presence of infiltrating leucocytes; (2) the formation of sarcoplasmic projections at the ends of damaged myofibres is dependent on leucocyte infiltration; (3) nuclei in the sarcoplasmic projections are probably derived from fusion of muscle precursor cells; (4) most muscle precursor cells in vivo replicate at least once before fusion; and (5) both replication and fusion of muscle precursors can occur in the absence of infiltrating leucocytes. These results are discussed with respect to the interaction of various cell populations during regeneration of skeletal muscle, and are of clinical significance to pathological changes seen in many myopathies.


Behaviour of osteoclasts in vitro: contact behaviour of osteoclasts with osteoblast-like cells and networking of osteoclasts for 3D orientation.

The cell-cell contact-induced behaviour of osteoclasts and osteoblasts in vitro was investigated by time-lapse videomicroscopy. Contact interactions of osteoclasts with autologous cells, derived mostly from chick but also from rat bones, included contact inhibition, failure of contact inhibition, contact guidance along stabilised edges of other cells, and underlapping of other cells. Message-mediated contact behaviour (MMCB) between osteoclasts and autologous osteoblastic cells resulted, after a time delay, in zeiosis of the osteoblast-like cell which could continue, or even begin, after the osteoclast broke contact, leading to retraction of the cell and occupation of its position by the osteoclast. MMCB may play a part in the breaching of the osteoblastic sheet by osteoclasts and, in general, in the malignant spread of neoplastic cells. Two or more osteoclasts were often joined by connecting and coordinating tubules (CCTs) of varied, and varying, lengths and widths. Osteoclasts could travel along the CCTs in both directions, or send nuclei through them. The CCTs became temporarily attached to the surface of other cells, or to the substrate, then acting as a temporary anchorage for orientation and for the return of the cell to the same spot. The dynamics of osteoclastic behaviour suggest that such a networking of osteoclasts is valuable for the 3D coordination of their role in bone turnover.


Calcium phosphate crystal distribution in the superficial zone of human femoral head articular cartilage.

The distribution of cuboid crystals in articular cartilage was examined by image analysis of electron micrographs. The specimens were considered to be functionally normal articular cartilage from femoral heads resected either because of femoral neck fracture or tumour in the distal femur. The study was restricted to the superficial region between 0 and 50 microns depth. Crystals were present in all specimens regardless of the age of the patient. The crystal profile area density was significantly greater in superior region samples than inferior region samples and this difference was less in older specimens. A band of microcrystals 10-20 microns below the articular surface was observed in superior samples. A significant correlation between mean individual crystal profile area and age was observed. It is noted that crystals are present in regions of cartilage subject to high mechanical stress.


Zonal differentiation of the marmoset (Callithrix jacchus) endometrium.

The differentiation of the marmoset (Callithrix jacchus) endometrium under different steroid hormone levels was investigated by electron microscopy and by the binding of different antibodies directed against collagen types. Based on differences in the glandular and interglandular compartments, the endometrium of sexually mature common marmosets consists of 3 zones: basal, adluminal and luminal. Hormone-dependent appearances are characterised. With low steroid concentrations, intercellular spaces between glandular epithelial cells occurred in the adluminal and the luminal areas. Epithelial cells of the basal region exhibited coated pits and phagolysosomes together with large apical protrusions. Under oestrogen dominance, phagolysosomes, fat vesicles and apical protrusions were evident in epithelial cells in the adluminal region. Secretory granules and concentric glycogen accumulations were a characteristic feature in epithelial cells of the adluminal and basal regions. With high progesterone concentrations, large empty vesicles were found with a higher frequency in adluminal than in basal epithelial cells. Using FITC-labelled antibodies against types V and VI collagen, binding was apparent adluminally in close vicinity to basement membranes, whereas reactivity was seen in the entire interglandular region of the basal area during this phase. Our findings indicate specific microenvironments with distinctive structural characteristics in the marmoset endometrium that are hormone dependent during all phases of the endometrial cycle. They are not related to menstruation, appear to be characteristic for primates and could reflect epithelial-mesenchymal interaction.


In vivo interaction of cationised ferritin with the surface coat and endocytosis by pulmonary intravascular macrophages: a tracer kinetic study.

The pulmonary intravascular macrophages (PIMs) of goat lung contain a unique electron-dense coat consisting of globular units arranged in a linear fashion along the cell surface. The globules showed a high affinity for cationised ferritin (CF) within 2-5 min of its intravenous injection, whereas native ferritin did not bind with the globules of the coat. The CF-labelled (hybrid) globules were subsequently internalised via receptor-mediated endocytosis. During 2-5 min of CF treatment, hybrid globules rapidly reached endosomes, multivesicular bodies and lysosomes, which acquired a high visibility in the form of interconnected tubular structures in the area of the Golgi complex. It is suggested that globular units of the surface coat, by showing high affinity for CF, resemble negatively charged large low density lipoprotein molecules. It supports our earlier postulate that heparin and lipolytic lipase sensitive globules of the surface coat of PIMs may be composed of lipoprotein-like substances. The ubiquity of the surface coat as a differentiated surface structure perhaps enables PIMs to cope with a barrage of stimulatory and suppressive signals within the microcirculatory units of the lungs of these animals.


Fibre type composition of the soleus muscle in hypoxia-acclimatised rats.

Fibre type composition in the soleus muscle was studied in second generation male and female Sprague-Dawley rats bred at 460 Torr (hypobaric hypoxia). In control male and female rats (bred at sea level atmospheric pressure) the percentage of slow twitch oxidative (SO) fibres increased, and the percentage of fast twitch oxidative glycolytic (FOG) fibres decreased over time. In male hypoxic rats fibre type composition did not change. However, in female hypoxic rats the percentage of SO fibres increased, and that of FOG fibres decreased over time. The female hypoxic rats had a higher percentage of FOG fibres and a lower percentage of SO fibres than age-matched control rats. These findings indicate that hypoxia-acclimatised rats have a relatively high percentage of FOG fibres, and that this is due to inhibition of the fibre type shift from FOG to SO, which occurs during normal development. Furthermore, there is a sex-related difference in the change in fibre type composition in hypoxia-acclimatised rats.


Comparative study of renin expression in the coagulating glands of C57BL/6 and Balb/c mice.

The comparative localisation of renin in the genital organs, especially in the coagulating glands of male mice of the strains C57BL/6 and Balb/c, was investigated using immunocytochemical, immunoelectron microscopical and Northern blot techniques. Dot-like reactions for renin, of varying diameters, were detected immunocytochemically in the epithelial cells of coagulating glands of C57BL/6 mice, but not in those of Balb/c mice. In both strains, many electron dense granules differing in content and morphology were observed in the epithelial cells of the coagulating glands. Crystalline materials were sometimes contained in these granules. Colloidal gold particles indicating the presence of renin were detected in the electron dense granules of C57BL/6 mice, in which they showed a heterogeneous distribution and were especially located on the crystalline structure. No positive reaction was detected in these crystalline structures in Balb/c mice. Renin mRNA was detected in the coagulating glands of both C57BL/6 and Balb/c mice by Northern blot analysis. However, the expression in C57BL/6 coagulating glands was stronger than that in Balb/c. These findings suggest that renin is synthesised and released in the coagulating glands.


Lanthanum tracer and freeze-fracture studies suggest that compartmentalisation of early bone matrix may be related to initial mineralisation.

In adult bone the calcified matrix and enclosed osteocytes are separated from the extracellular space by a continuous layer of bone lining cells. It thus appears that bone matrix is compartmentalised and, as such, may constitute a 'milieu intérieur' which is different from the general extracellular space. Since adult bone matrix is compartmentalised and matrix vesicles also form a microcompartment, it is conceivable that compartmentalisation, in early osteogenesis, may be a requirement for the initial events of the mineralisation process. We have therefore conducted an ultrastructural, tracer, and freeze-fracture study to determine the stage in which bone matrix becomes compartmentalised and also to find out whether there are tight junctions between osteoblasts. The results show that in early nonmineralised stages and in incipient mineralisation, lanthanum penetrates all intercellular spaces and the newly forming bone matrix which is rich in matrix vesicles and collagen. With the progression of mineralisation, when all matrix vesicles appear mineralised and calcification is 'spreading' to the surrounding matrix, lanthanum is restricted to intercellular spaces and conspicuous macular tight junctions are present between osteoblasts. We suggest that matrix vesicles act as microcompartments for calcification when the early bone matrix is in continuity with the surrounding extracellular space. In later stages, when lanthanum fails to penetrate the matrix, matrix vesicles may no longer be necessary because the bone matrix itself is compartmentalised, thus allowing for localised changes in composition that might favour mineral deposition.


Quantitative analysis of rough endoplasmic reticulum in chondrocytes of articular and tracheal cartilage of rabbits following the systemic administration of hydrocortisone.

The rough endoplasmic reticulum (RER) in chondrocytes was analysed stereologically in articular cartilage of knee joints and in tracheal cartilage of rabbits injected intramuscularly with 5 mg/kg hydrocortisone daily for 4 wk. In articular cartilage, RER area per unit cytoplasmic volume decreased in chondrocytes in all (superficial, middle and deep) zones, although the volume of glycogen deposits per unit cytoplasmic volume increased in the middle and deep zones. RER area per chondrocyte also decreased in the 3 zones without changes in average chondrocyte volume in the superficial and deep zones. Furthermore, the volume of glycogen deposits per chondrocyte did not alter in the 3 zones. These indicate a reduction of RER area in articular chondrocytes after hydrocortisone administration and suggest a decrease in the protein-synthesising capacity of these cells. In tracheal cartilage in which 2 zones were identifiable, RER area per unit cytoplasmic volume decreased in chondrocytes in both the superficial and main zones without changes in the volume of glycogen deposits per unit cytoplasmic volume. In addition, RER area per chondrocyte decreased in the main zone. The results suggest that the decrease in RER area in chondrocytes after corticosteroid administration is not specific to articular cartilage but is common to cartilage in various organs.


Leydig cells in the lingual epithelium of the axolotl, Ambystoma mexicanum, are immunoreactive for serotonin.

The Leydig cells in the lingual epithelium of the axolotl were investigated by immunohistochemistry using serotonin antiserum. Serotonin-immunoreactivity was found in their secretory granules. The physiological role of serotonin in the Leydig cell, a type of exocrine cell, is unknown.


Magnetic resonance imaging of the saccular otolithic mass.

The frog's inner ear was studied in vivo by high spatial resolution magnetic resonance imaging at 7 Tesla. The vestibule, the internal acoustic meatus, and the auditory tube have been identified. The large otolithic mass contained in the vestibule showed a virtual absence of magnetic resonance signal probably due to its composition of closely packed otoconia.