Activity of antibiotics against resistant Pseudomonas aeruginosa.

The activity of 12 antibiotics, piperacillin, cefazolin, cefotiam, ceftizoxime, latamoxef, ceftazidime, cefuzonam, amikacin, ofloxacin, imipenem, aztreonam and minocycline, against 120 isolates of Pseudomonas aeruginosa was examined. In addition, the efficacy of antibiotics against single-, double-, or triple-drug-resistant isolates of P. aeruginosa were also examined to determine the cross-resistance to each drug. There was cross-resistance between piperacillin, ceftazidime and aztreonam, but amikacin and imipenem remained effective antibiotics, especially as salvage therapy, against isolates resistant to one agent. Results also suggested that piperacillin, ceftazidime or imipenem in combination with amikacin are effective combination regimens against most clinical isolates of P. aeruginosa. Amikacin and imipenem were also suitable antibiotics, especially as salvage therapy, against isolates of P. aeruginosa resistant to two agents. In conclusion, the results provide useful guidelines for choosing an effective treatment against clinical isolates of P. aeruginosa, and for choosing salvage therapy against resistant P. aeruginosa.


Ceftazidime and amikacin as empiric treatment of febrile episodes in neutropenic patients in Saudi Arabia.

Sixty-four consecutive febrile episodes in 50 consecutive patients with malignancy and neutropenia were empirically treated with a combination of ceftazidime and amikacin. Of 52 analysable episodes, the response rate was 59.6% overall and 26.3% of episodes with microbiologically documented infections with septicaemia. Infection-related death occurred in 10 patients (19.2% of episodes). The response rates were similar in patients with acute leukaemia or other malignancies. Poor response is attributed to increased frequency of infections with Gram-positive and fungal organisms. A modified empiric regimen including cover for Gram-positive and fungal organisms is suggested in similar patient populations.


Copulatory behavior, reproduction, and sperm competition in two strains of male rats.

Long-Evans males fathered 72% of the offspring when one Long-Evans and one F344 male mated repeatedly with the same female throughout her estrus. When each male was restricted to one ejaculation and the second male was allowed to begin mating immediately following the first male's ejaculation, the second male left more offspring in each strain. However, the proportion was significantly greater for Long-Evans males. In contrast, there were no strain differences in either number of pregnancies or litter size in noncompetitive matings limited to two ejaculations, the minimal number required to induce pregnancy. The only consistent behavioral differences were the greater number of intromissions performed with shorter latencies by F344 males, differences that cannot readily be used to explain their reduced success. It was hypothesized that the two strains may differ in the adequacy of penile reflexes used to form, set, or dislodge sperm plugs.


Morphological variability and developmental aspects of monkey and human granule cells: differences between the rodent and primate dentate gyrus.

The postnatal generation, dendritic development and morphological variability of granule cells were studied in the monkey and human dentate gyrus. Granule cells are mainly formed prenatally in primates with an approximate 4- to 6-month postnatal generation time in humans. Dendritic development of individual granule cells appears to be prolonged over a long period of time. Immature granule cells were observed as late as in 15-month-old children. The morphological variability of granule cells is similar in monkeys and humans. Both display granule cells with basal dendrites as well as granule cells with different dendritic lengths and spine densities. The prolonged development of the spine structure of the human mossy cells suggests that synaptic connections between granule cells and their postsynaptic target neurons develop through a long postnatal period of time that may last as long as 5 years postnatally. The morphological variability of granule cells in primates should be considered when drawing conclusions about hippocampal neuropathology. The prolonged development of the neurons and neuronal circuitries in the human dentate gyrus may cause the lack of adult-like memory formation in early childhood resulting in the phenomenon of 'infantile amnesia'.


Graft engineering: the evolution of hematopoietic transplantation.

In vivo therapeutic manipulation as well as ex vivo grafting are important strategies for bone marrow manipulation and transplantation. This review article discusses the early techniques for marrow processing and manipulation as a background for discussing later graft engineering protocols, as well as preclinical and experimental protocols designed to modify transplantation biology at the multidisciplinary level. The direction of future trials in graft transplantation is also discussed.


Cyclophosphamide mobilization of peripheral blood stem cells for use in autologous transplantation after high-dose chemotherapy: clinical results in patients with contaminated or hypocellular bone marrow.

Peripheral blood stem cells (PBSC) can be used for hematopoietic reconstitution in patients who have received high-dose chemotherapy (HDC). Previously, we reported 18 such patients who had nonmobilized PBSC harvested in steady state. We have now performed PBSC reinfusion in 24 patients with hypocellular or tumor-involved marrow who received cyclophosphamide (Cy) mobilization (4 grams/m2) prior to PBSC collection. The PBSC were collected upon rebound hematopoietic recovery by continuous-flow leukapheresis and subsequently cryoproserved. A median of 3.17 x 10(8) mononuclear cells/kg (range 1.47-3.95 x 10(8)) were collected. Patients underwent a median of 6 apheresis procedures (range 5-12). To date all 24 patients have undergone PBSC reinfusion after HDC. Fourteen patients received post-reinfusion granulocyte/macrophage colony-stimulating factor. Granulocyte recovery (> 500 x 10(6)/ml) has occurred at a median of 13.5 days (range 7-39) and platelet recovery (> 50 x 10(9)/ml without transfusion support) has occurred in 20 patients at a median of 33 days (range 7-121 days). Four other patients have platelet counts of greater than 20K and are transfusion independent, but have still not achieved counts of 50K. PBSC collection after Cy mobilization is feasible and effective for hematopoietic reconstitution after HDC and reinfusion. All 24 patients demonstrated trilineage engraftment. Although neutrophil recovery was not significantly hastened (as compared with our nonmobilized or steady-state data), time to platelet engraftment was foreshortened.


Immunomagnetic manipulation of hematopoietic cells: a review of current technology.

During the last decade, immunomagnetic separation of cells has become popular due to the simplicity and speed of the technology. A variety of magnetic materials have been developed that have fundamentally different characteristics. Some of these act as true colloids and have the properties of solutions, while others are larger and are based on the polymerization of materials, such as styrene, in the presence of magnetite. In this article, the different magnetic matrices are discussed and reviewed with respect to their use for the separation of cells of the hematopoietic system. Additionally, a brief introduction into the field of immunomagnetic separation of nucleic acids is presented, as this technology may be used to perform investigations at the molecular level on hematopoietic cells.


Purging of autologous bone marrow for transplantation: the protection and selection of the hematopoietic progenitor cell.

Autologous bone marrow transplantation (ABMT) is the treatment of choice for selected patients with acute myelogenous leukemia, non-Hodgkin's lymphoma, and poor prognosis breast cancer. A possible limitation of this approach is that clonogenic tumor cells could be collected and infused back into the patient along with the normal bone marrow. The major emphasis in our laboratory has been the development of marrow purging regimens for breast cancer patients. This paper describes two investigative approaches hematopoietic progenitor cell protection and selection. We describe how the use of G-CSF in the patients who receive positively selected marrow shortens the rate of engraftment.


Quantitation of tumor cell removal from bone marrow: a preclinical model.

We have developed a multiassay system consisting of fluorescence microscopy, immunocytology and tumor colony assay to monitor the removal of tumor cells from bone marrow. This system was tested in preclinical purging experiments in which neuroblastoma cells were seeded into bovine marrow and purged by treatment with monoclonal antibodies and immunomagnetic beads. Eight experiments were performed on two different neuroblastoma cell lines seeded at 2% and/or 5% contamination. We consistently demonstrated greater than a 3 log removal with one cycle of antibody/bead treatment and greater than a 1 log further reduction by addition of a second cycle. We also demonstrated removal of all detectable tumor stem cells by this purging method. We feel that this system will prove valuable for monitoring ex vivo tumor removal in future clinical studies and should be considered for use in other purging trials.


Interferon-gamma potentiates the antitumor effect of cyclosporine-induced autoimmunity.

Graft-versus-host-disease (GVHD), which results after allogeneic bone marrow transplantation (BMT), is associated with reduced leukemic relapse. This may be mediated by an immunologic attack with subsequent destruction of residual tumor cells. On the other hand, GVHD does not normally occur after autologous BMT (ABMT), which has an inherently high relapse rate. However, an autoimmune syndrome (AIS) similar to GVHD can be induced after autologous/syngeneic BMT by administration of cyclosporine-A (CsA), resulting in the production of major histocompatibility complex (MHC) class II or Ia autoreactive cytolytic effector cells. Since many hematopoietic malignancies express variable levels of class II molecules, we hypothesized that the adjuvant use of interferon-gamma (IFN-gamma) with CsA-induced autoimmunity after autologous/syngeneic BMT may upregulate class II antigens on residual tumor cells and make them more susceptible to attack by the Ia-reactive cells of CsA-induced AIS. The present studies demonstrated that the CsA-induced autoimmune syndrome mediated an anti-tumor effect, although this effect was dependent on challenge with a minimal number of tumor cells. Further studies clearly demonstrated that the antitumor effect could be markedly enhanced by administration of IFN-gamma which increased the susceptibility of the tumor to recognition and lysis by the CsA induced autoimmune effector cells. The induction of MHC class II-restricted AIS similar to GVHD by administration of CsA together with the ability to manipulate the surface phenotype of residual tumor cells may lead to decreased relapse rates in the ABMT setting.


Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32).

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)


Animal models for human hematopoiesis.

Despite seminal contributions provided by in vitro studies to the field of hematopoiesis, our present knowledge of mammalian lymphohemopoiesis and the mechanisms governing differentiation and self-renewal of hematopoietic stem cells has been derived in most part from elegant in vivo studies. The inability to apply such an approach to the examination of the human hematopoietic system is the primary reason why several aspects of human hematopoiesis including human stem cell biology are still poorly understood. To overcome the inability to probe human hematopoiesis in vivo, researchers have "humanized" animals via the transplantation of human hematopoietic progenitor cells and other tissues in an attempt to create human-animal chimera suitable for investigating human lymphohematopoiesis in vivo. To date, several of these "humanized" animal models have been developed. During their relatively short existence, human-animal models have contributed substantially to the field of experimental hematology. The development, peculiarities, shortcomings, and applications of these animal models as well as their potential use in exploring the field of human lymphohematopoiesis are the focus of this review.


Retroviral vector-mediated gene transfer into hematopoietic cells: prospects and issues.

Gene therapy is a developing technology that may allow the treatment of a variety of congenital and acquired genetic disorders as well as infectious diseases through the introduction of exogenous genetic material into relevant cellular populations. Currently, the most effective method for gene transfer into cells of the hematopoietic system is with retroviral vectors. Appropriate cellular targets for gene transfer include totipotent hematopoietic stem cells as well as long-lived lineage committed cells such as T lymphocytes. Although retroviral vector-mediated gene transfer into totipotent stem cells and subsequent long-term expression of transduced genetic material in stem cell progeny has been observed in murine bone marrow transplantation experiments, similar observations have not been made in clinically relevant large-animal models. A number of recent advances in gene delivery systems, purification of stem cells, defining extramedullary sources of stem cells, characterizing the biologic processes that regulate the proliferation and developmental potential of stem cells, and construction of more effective models for assessing stem cells, may result in improvements in gene transfer into large animal and human totipotent stem cells.


Umbilical cord and placental blood hematopoietic stem cells: collection, cryopreservation, and storage.

Human umbilical cord and placental blood is a rich source of hematopoietic stem cells that can be used to reconstitute hematopoiesis after intensive myeloablative therapy. Therefore, it has become necessary to develop techniques for (i) collecting large volumes of umbilical cord aseptically, (ii) optimizing the yield of viable cells after cryopreservation and thawing, and (iii) minimizing the risk of maternal T-cell contamination. Our protocol for the collection, cryopreservation, storage, and transport of human umbilical cord and placental blood is described in detail.


Enumeration of cells in bone marrow and peripheral blood stem cell collections: technical issues and prospects for standardization.

Enumeration of total nucleated cells and mononuclear cells is a fundamental part of the laboratory evaluation and quality control program for bone marrow and peripheral blood stem cell collections intended for transplantation. Measurement of the total nucleated cell content is especially useful for providing rapid feedback about the bone marrow product during or immediately after the harvest. However, the mononuclear cell content may be more informative because the nucleated cell population contains a variable number of mature granulocytes and nucleated red cells, which do not contribute to hematopoietic engraftment. The lack of comparative data among various laboratories and among different types of cell counting methods has hindered standardization of these assays among bone marrow processing laboratories. Specific issues needing attention in assay standardization include sample preparation and handling, identification and elimination of artifacts in automated counting, relative advantages and disadvantages of manual and automated counting methods, and criteria for differential counting of nucleated cells. The establishment of standards for bone marrow and other stem cell counting methods, as well as other evaluation procedures, should be preceded by collection and analysis of comparative data, and followed by a proficiency testing program for bone marrow processing laboratories.


Autologous graft engineering.

Autologous transplantation of bone marrow or peripheral blood stem cell preparations is now a widely used form of rescue from the myeloablative effects of high-dose therapy for malignant disease. The success of this procedure is affected by numerous factors associated both with management of the patient and the quality of the graft. In this review, approaches are described to maximize the success and utility of this therapeutic approach.


The regulation of hematopoietic stem cell collection and storage: the New York State approach.

In December 1988, the New York State (NYS) regulatory code on bone marrow banking went into effect. The goals of the regulations were to codify a high standard of practice, to prohibit charlatanism in the practice or promotion of stem cell banking, and to promote legitimate research. The NYS approach modeled the stem cell regulatory language after that already established for blood banks and clinical laboratories. Also, the stem cell standards are an element of standards applicable to all tissue banks, developed as a result of a comprehensive transplant law enacted in NYS in 1990. The code itself, published as an addendum to this article, mandates that a qualified (by training and experience) medical director and medical advisory committee be appointed, and gives broad and complete responsibility for the services provided to that medical director. Explicit written policies and procedures regarding administrative, technical, safety, and quality issues are necessary, but regulatory micromanagement of the laboratory was avoided by limiting detailed procedural requirements. We believe that these regulations have contributed to the quality and safety of stem cell-related therapies in NYS.


Bone marrow and peripheral blood stem cell harvesting.

A number of malignant diseases are responsive to supralethal myelotoxic high-dose chemoradiotherapy, and can be treated with hematopoietic stem cell rescue. The number of genetic diseases correctable by replacement of defective pluripotent stem cells with normal stem cells or through gene transfer is ever-increasing. In all these cases, pluripotent hematopoietic stem cells need to be infused, which can be obtained directly from the bone marrow or from the peripheral blood with or without the aid of mobilizing strategies. This article is a detailed review of the technical and medical aspects of stem cell collection from the bone marrow and the peripheral blood.


The risk of tumor cell contamination in peripheral blood stem cell collections.

Peripheral blood stem cell (PBSC) reinfusions are being used with increasing frequency in lieu of, or in addition to, autologous bone marrow transplantation (ABMT) to rescue cancer patients from the myeloablative effects of high-dose chemotherapy. However, the incidence and quantity of tumor cell contamination in PBSC collections has not been widely investigated. This paper reviews the existing data and presents new information to demonstrate that tumor cells are detectable in PBSC harvests from patients with a variety of malignancies. Furthermore, their presence in peripheral blood may have prognostic and clinical significance. Areas of future research and applications for PBSC technologies are also discussed.


Hematopoietic stem cell cryopreservation: a review of current techniques.

Hematopoietic stem cells (HSC) can be stored for prolonged periods at cryogenic temperatures. The techniques currently used were derived from the initial report in 1949 of cryopreservation of bovine sperm in glycerol. The addition of this penetrating cryoprotectant protected the cells from the injury associated with ice formation. Current cryopreservation techniques (with minor variations) suspend cells in an aqueous solution of salts, protein, and one or more cryoprotectants. Cells are frozen at slow rates and stored generally below -120 degrees C in mechanical freezers or nitrogen refrigerators. That these techniques are successful in maintaining HSC viability is evident from the engraftment of these cells in patients treated with marrow-lethal conditioning regimens. However, issues such as the composition of the cryoprotectant solution, cell concentration during freezing, cryoprotectant toxicity, and storage temperatures have not been adequately studied, primarily because of a lack of appropriate assays for HSC cryosurvival. HSC cryobiology will become an increasingly important subject as new HSC collection and processing techniques are developed. Improved cryosurvival of HSC using modified cryoprotectant solutions may improve engraftment kinetics and decrease the cost and morbidity of autologous transplantation.


Ex vivo expansion and differentiation of hematopoietic stem cells.

Hematopoietic stem cells are phenotypically very heterogeneous, probably reflecting the degree of activation and/or differentiation. This cell population is capable of high-level proliferative activity and multilineage differentiation. Despite its potential for self-renewal, the hematopoietic stem cell exists in a quiescent state for prolonged periods of time. The mechanism(s) involved in triggering these cells to enter the cell cycle is/are not totally clear; however, cytokines (both positive and negative regulators) are implicated. Most, if not all known cytokines that interact at the stem cell level do so not only by inducing proliferation but also differentiation. The ability to maintain a population of truly primitive stem cells for extended periods of time in vitro is currently under investigation by many research groups.


Recombinant human granulocyte-macrophage colony-stimulating factor stimulates superoxide anion and hydrogen peroxide production in human neutrophils.

The effect of purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the oxidative metabolism of human peripheral blood granulocytes was investigated. The respiratory burst of granulocytes was assessed in individual cells by flow cytometry utilizing the oxidation of the nonfluorescent 2',7'-dichlorofluorescein (DCFH) to the highly fluorescent DCF by hydrogen peroxide (H2O2). Treatment with GM-CSF caused granulocytes to produce H2O2 without addition of a second stimulus. The amount of H2O2 produced correlated with the concentration of GM-CSF administered. Also, GM-CSF did not prime the granulocytes for enhanced H2O2 production in response to N-formylmethionyl-leucyl-phenylalanine (f-MLP). Consecutive stimulation of granulocytes with GM-CSF and f-MLP resulted in additive production of H2O2. GM-CSF also induced granulocytes to release superoxide anion (O2-) in a dose-dependent manner, when the respiratory burst was assessed by a conventional cytochrome c reduction assay. In contrast to hydrogen superoxide production, GM-CSF significantly (p < 0.001) enhanced f-MLP-stimulated release of superoxide anion over that expected from the additive effects of the two agonists.


Bone marrow processing with the Fresenius AS 104: initial results.

Prior to purging, cryopreservation, or ABO-incompatible bone marrow (BM) transplantation, we have concentrated 23 BM harvests using a modification of the "grancollect-protocol" and the recently available bone marrow stem cell (BMSC) protocol of the Fresenius AS 104 cell separator with the P1-Y set. Within 40-70 minutes, the initial marrow volume of 922 ml (+/- 408 ml) was processed two to three times. A mean of 59% (+/- 20%) of the initial mononuclear cells was recovered in a mean volume of 119 ml (+/- 31 ml). The recovery of clonogenic cells, measured by CFU-GM assays, was 98% (+/- 80%). Red blood cells in the BM concentrates were reduced to 8% (+/- 4%) of the initial number. The procedure was efficient and yielded a BM cell fraction suitable for purging, cryopreservation, and transplantation. All transplanted patients showed fast and sustained engraftments after autologous or allogeneic BM transplantation.


Counterflow centrifugal elutriation: experimental and clinical applications.

Counterflow centrifugal elutriation (CCE) separates mixed cell populations into distinct subpopulations, on the basis of different sedimentation characteristics, without impairment of cell function or yield. The advantages of this technique are the high recovery and viability of fractionated cells, as well as the rapidity and the reproducibility of results. CCE alone, or in combination with other separation methods, can provide homogeneous populations of cells for further investigations. Recently, CCE was employed in clinical studies aimed at preventing graft-versus-host disease in bone marrow transplant recipients, by depleting lymphocytes prior to bone marrow infusion. This article reviews the principles of elutriation and describes the possible experimental and clinical applications of this technique, which seems suitable for both peripheral blood (PB) and bone marrow (BM) separation.


Colony-forming unit culture of bone marrow and peripheral blood stem cells: comparison of commercially available media.

Increased utilization of the granulocyte-macrophage colony-forming unit (CFU-GM) assay for quality control, dosing, and clinical investigation of peripheral blood (PB) stem cell and bone marrow (BM) products led us to compare two commercially available media ("Ready-Mix" [RM] from Terry Fox, Vancouver, Canada and Stem Cell CFU Kit [SCCK]) from GIBCO, Grand Island, NY-Baxter Healthcare Corp., Deerfield, IL) to our standard laboratory media (SLM). Aliquots of mononuclear cells (MNC) from PB and BM donors were cultured in triplicate in the three media and CFU-GM and erythroid burst-forming units (BFU-E) were enumerated. Similar colony growth was achieved in all media for PB; modestly increased BM CFU-GM were noted in SCCK. SCCK and RM are easy to use, are commercially available with lot-controlled conditioned media (PHA-LCM), and may facilitate the standardization of CFU assays in blood banks and bone marrow processing laboratories.


Clinical and experimental approaches to varieties of memory.

Memory is described as a complex aspect of cognitive functioning. Memory is dependent upon input from the sensory modalities; it relies upon the passage of time; and it requires intervening processes for initial acquisition and subsequent access. Based upon questions posed concerning the relationship between clinical and experimental advances in memory and memory disorders, an example is given to illustrate the influence of research upon techniques for diagnosis and rehabilitation. Suggestions are provided about how to approach answering other related questions in neuropsychology. An integrated program is suggested with the aim of bringing together findings from neuroanatomy, neurochemistry, and neurobehavior. Emphasis is placed upon integrating results of research based upon human and nonhuman models of disordered memory and other cognitive functions. Neuroanatomical systems important for performing delayed-reaction tasks are reviewed, as are results of delayed response and delayed alternation testing in several human populations with neurological dysfunction suggestive of frontal lobe damage.


The relationships between nonverbal intelligence and the strength of left-hand preference in left-handers to sex and familial sinistrality.

The relationship between the strength of left-handedness and spatial reasoning ability was studied in left-handed male and female subjects with and without familial sinistrality (FS). The degree of left-handedness was assessed by the Edinburgh Handedness Inventory. The spatial reasoning ability was measured by Cattell's Culture Fair Intelligence Test. It was found that there was a negative linear correlation between nonverbal IQ and the strength of left-handedness in females with and without FS, a quadratic relationship in male left-handers without FS and a positive linear correlation in male left-handers with FS. These results indicate that the brain may exhibit different patterns of cerebral organization in left-handers to sex and FS. It was concluded that the "crowding" hypothesis may apply only to a subgroup of left-handers, i.e., females with a greater bilaterality of cognitive functions than males.


A straight nasal septum and right unilateral hypertrophied inferior nasal turbinate, a very rare anatomical phenomenon, in skilled language translators: relevance to anomalous dominance, brain hemisphericity and second language acquisition.

Research on second language acquisition has recently focused on the concept of brain hemisphericity. Since the nasal cycle indexes brain hemisphericity and a deviated nasal septum itself affected by structural brain dominance may prevent nasal cycling, we investigated the presence of septal deviation and inferior turbinate hypertrophy in 11 expert translators. We found that 10 of the 11 subjects demonstrated both a straight nasal septum and right unilateral inferior turbinate hypertrophy, an extremely rare anatomical phenomenon. The one-tailed binomial test was extremely significant (p < .0000001). This anatomical phenomenon, which can be noninvasively checked in less than 30 seconds may predict excellence in second language acquisition.


Muscle morphometry in amyotrophic lateral sclerosis.

Quadriceps muscle biopsies from 24 patients with amyotrophic lateral sclerosis (ALS) and 15 age-matched controls were prepared for histochemistry and analyzed morphometrically. Pathological features for denervation and reinnervation were observed in most ALS patients, although considerable variation between patients was noted. Myopathic changes were also seen in one-third of the cases. The morphometric data were not only related to the duration and mean diameter of type I fiber, but also to the duration and hypertrophy factor of type II fiber, suggesting that the progression and severity of ALS depends on the preservation of both fibers.


Maturation rate and spatial, verbal, and musical abilities: a seven-year-longitudinal study.

We traced spatial, verbal and musical abilities through a seven-year period of adolescence. When we started our study, 60 boys had reached a mean age of 11.72, 60 girls were 11.52 on average. Menarche and mutation served as markers for maturation. We found that early, mid, and late maturers differed on spatial orientation and on tactile-visual discrimination as measured with the Witelson task. No differences between the maturational groups emerged on verbal fluency and on Wing's Standardized Tests of Musical Intelligence. At some stages, sex differences on spatial, verbal, and musical tests emerged, and disappeared at others. The sex differences in performance levels were not associated with a sex-specific relationship between maturation rate and performance levels. We found indications of the usefulness of sex hormone measurement in relation to cognitive and musical development in adolescence.


Functional impairment of the rat superior colliculus after kainic acid intraocular injection: a 2-deoxyglucose study.

Long Evans rats monocularly injected with the kainic acid (KA), were exposed to "tonic" (diffuse steady light, stationary pattern, total darkness) and "phasic" (flashing, moving pattern) stimulations. By means of the autoradiographic 2-deoxyglucose (2DG) technique we assessed the functional activity of the Superior Colliculus (SC) contralateral to the injected eye as compared to the normal eye SC. In the control SC all "tonic" stimulations determined low 2DG uptake not modified by the intraocular KA injection. On the contrary, "phasic" stimulations elicited a strong 2DG consumption in the normal SC, with a peculiar pattern of distribution depending on the kind of stimulus. Considering the total 2DG uptake as the added intrinsic and afferent metabolism, KA was able to affect only the latter, decreasing two-fold that expected for the afferent input loss. These findings can suggest a possible KA effect on off-line ganglion cells and, on the other side, they confirm the role of the SC in discriminating "phasic" and sudden phenomena from "tonic" and continuous ones.


Serum testosterone levels in male and female subjects with standard and anomalous dominance.

Serum testosterone levels were determined in female and male subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. Subjects with anomalous dominance (left-handers, mixed-handers, and right-handers with familial sinistrality) were compared to subjects with standard dominance (right-handers without familial sinistrality). The mean serum testosterone levels were found to be significantly higher in subjects with anomalous dominance than those with standard dominance. It was concluded that the results are in accord with the testosterone hypothesis of cerebral lateralization.


The relationship of pineal calcification and melatonin secretion to the pathophysiology of tardive dyskinesia and Tourette's syndrome.

Despite current intensive research, the pathophysiology of tardive dyskinesia (TD), a serious neurological side effect of neuroleptic treatment, is poorly understood. Prompted by the observation of an increased incidence and severity of abnormal perioral movements in neuroleptic-treated pinealectomized, as compared to intact rats, we suggested that the pineal gland exerts a protective effect which mitigates against the development of TD and, by inference, that reduced melatonin secretion may be related to the pathophysiology of TD. To investigate this proposition further, we studied the association of TD with pineal calcification (PC) on CT scan in chronic schizophrenic patients. Our findings revealed a significant association between TD and PC and suggest, furthermore, that PC may be a neuroradiological marker of TD. Since PC may reflect diminished secretory activity of the gland, these findings support the hypothesis that the pathophysiology of TD is linked to disturbances of melatonin secretion. The clinical and therapeutic implications of these novel findings are discussed. In the following communication, in which we introduce the hypothesis that disturbances of 5-HT and melatonin secretion are related to the pathophysiology of TD. Subsequently, we present a series of studies which relate to the association of TD with PC. We conclude by presenting the hypothesis that disturbances in melatonin secretion may also be relevant to the pathophysiology of Tourette's syndrome.


Muscle derived motoneuron trophic factors promote the survival of motoneurons in vitro only when serum is present in the growth medium.

Motoneuron cultures were established from E6 chick spinal cord. Motoneurons survived for less than 2 days in chemically defined medium. The addition of muscle extract to the medium supported the survival of only a small portion (approximately 2%) of motoneurons for 8 days in vitro. A similar low survival rate was observed when the growth medium was supplemented with serum. The addition of muscle extract to serum containing medium resulted in the survival of about 20% of the motoneurons for 8 days. No differences were seen in the ability of tissue extracts prepared from E8 hindlimb, or muscle obtained from E11, E15, E18 and P3 chicks to support motoneuron survival in the presence of serum. It is apparent that although there are trophic factors present in muscle that support motoneuron survival in vitro, the actions of such trophic factors are dependent upon the presence of yet other factors found in serum.


Contrast responses to bright slits of visual cells in the superior colliculus of the albino rat.

Contrast is the most effective stimulus in the visual system. The response of single cells to changes in stimulus contrast has been studied in a large variety of animals and the contrast response function determined. In the rat, studies on responses to contrast have been focused primarily in the geniculocortical pathway and there are relatively few in subcortical structures. We report here for the first time the contrast response function of single units located in the superior colliculus (SC) of the albino rat to several stimulus contrast. Cells in the SC require a relatively high contrast to elicit a reliable response and the dynamic response range is restricted to a short contrast interval.


Magnetic fields and seasonality of affective illness: implications for therapy.

Seasonal affective disorder is characterized by recurrent winter depression associated with hypersomnia, overeating, and carbohydrate craving. The severe form of winter depression affects about 5% of the general population and is believed to be caused by light deficiency. About 70%-80% of patients with winter depression experience attenuation of symptoms when exposed to bright light therapy. Hypotheses pertaining to the pathogenesis of winter depression implicate the effects of light on different characteristics of circadian rhythms. One of the environmental factors which may be implicated, in addition to light, in the pathophysiology of winter depression is the geomagnetic field. There is strong indication that the pineal gland is a magnetosensitive system and that changes in the ambient magnetic field alter melatonin secretion and synchronize the circadian rhythms. In man, shielding of the ambient magnetic field significantly desynchronizes circadian rhythms which could be gradually resynchronized after application of magnetic fields. The strength of the environmental magnetic field diminishes during the winter months, leading to increased susceptibility for desynchronization of circadian rhythms. Thus, since the acute application of magnetic fields in experimental animals resembles that of acute exposure to light with respect to melatonin secretion (i.e., suppression of melatonin secretion), magnetic treatment might be beneficial for patients with winter depression. In addition, since the environmental light and magnetic fields, which undergo diurnal and seasonal variations, influence the activity of the pineal gland, we propose that a synergistic effect of light and magnetic therapy in patients with winter depression would be more physiological and, therefore, superior to phototherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)


Oral syndrome: an incomplete form of cheiro-oral syndrome?

Cheiro-oral syndrome is a sensory disturbance observed around the corner of the mouth and the palm of the hand on the same side. We had an opportunity to observe a patient in whom sensory disturbance was limited only around the corner of the left mouth but not the hands or other findings. Computed tomography of the brain showed a low density area in the right thalamus. Could our case be called oral syndrome: incomplete form of cheiro-oral syndrome? We have to ask whether the our case is an oral syndrome or whether our case has to be regarded as a thalamic infarction.


Complex sensory cross integration deficits in a case of corpus callosum agenesis with bilateral language representation: positron-emission-tomography and neuropsychological findings.

A 45-year-old right-handed patient with total callosal agenesis and absence of the anterior commissure was examined neuropsychologically and with magnetic resonance and positron emission tomography (PET with 18FDG) of the brain. PET results showed, in the resting state, a bilateral metabolic reduction in the hippocampal formation and a left hemispheric reduction in the amygdala, thalamus and in the occipital and temporoparietal junction areas of the cerebral cortex. Under speech activation hypermetabolic glucose activity was observed bilaterally in the region of the Wernicke area and within the left Broca area. Neuropsychologically, on the whole the patient behaved normally, the exceptions being an inability to associate olfactory stimuli with words, a clear left ear advantage in dichotic listening, and a similar high performance in recognizing verbal stimuli presented tachistoscopically to either hemisphere. From comparing the patient's behavior with that of other acallosals it appears that highly individual variants of cerebral organization and/or reorganization result from the lack of the brain's main commissural system and that the processing of sensory information deviates considerably especially in cases in whom the two main telencephalic commissures--corpus callosum and anterior commissure--are absent.


Decerebrate rigidity with preserved cognition and gait: a possible role of anoxic-ischemic brain damage.

A case of stable decerebrate posture in the upper limbs following sudden loss of consciousness and prolonged coma is described. The patient recovered most of her cognitive functions and gait, without clinical, neurophysiological or neuroradiological evidence of brainstem lesion. MRI shows borderzone infarcts. It is suggested that anoxic-ischemic cortical damage, affecting specially corticoreticular neurons, could explain the development of decerebrate rigidity in patients without apparent brainstem lesion.


Concurrence of familial amyotrophic lateral sclerosis with Ribbing's disease.

We describe a case of familial amyotrophic lateral sclerosis associated with Ribbing's disease. This association has not been previously noted in the literature. The unusual feature of the case was that symptoms coexisted for several years before a correct diagnosis was made. The diagnosis was based on the clinical picture and the result of muscle biopsy and extensive radiographic study. This case serves to illustrate the fact that a separate problem should be considered when the clinical picture is not compatible with the underlying diagnosis.


[Supplementary feeding--additional food in daily infant nutrition].

A group of 707 children aged 1 to 24 months from the territory of Vojvodina (10 rural and urban settlements) was examined regarding additional food (nonmilk and milk food), time of introduction, infant's age and frequency of consumption. It has been concluded that supplementary feeding, including all food, starts early. Fruit and vegetable are introduced at the age of 34 months. As for the introduction of yolk (first given at about 4 months) it differs from the modern attitudes regarding the intake of this food. Milk formulae, meat and chicken liver are usually introduced about the fifth month. Analyses of the type of food and the way of preparation point to some extremities. Special emphasis is given to the environmental specificities which determine the recommendations.


[Morphologic characteristics of the liver allograft in experimental warm ischemia].

Thirty-minute normothermic liver ischemia causes swelling of the hepatocytes and sinusoid wall cells, their individual necrosis and discharge of the glycogen supply in the hepatocytes. The swelling of the hepatocytes and of the sinusoid wall cells causes a significant reduction of the liver lobe sinusoid volume which decreases from 27.6% to 5.4%, representing, actually, one fifth of the normal value. Such finding was recorded as a critical vascular liver volume, because any further decrease of the sinusoid volume would inevitably lead toward manifest and persisting portal hypertension which evidently interferes with Bernoulli trial of the hepatitic perfusion. The obtained data determine morphofunctional relevancy of the liver allograft for transplantation and are useful for all other surgical interventions requiring partial resection of this organ or time limited regional and total ischemia.


[Effect of polychemotherapy in the treatment of patients with non-Hodgkin's lymphoma].

Non-Hodgkin lymphomas belong to malignant hemopathies where clinical course, histological manifestation and therapy response are characterized by diverse features. Sensitivity of the lymphoma to chemotherapy introduced drug combinations for the improvement of patient survival rate and the prognosis. The study reviews the results achieved in 85 patients with NHL treated with different cytostatic combinations (COP, CHOP, COP-BLAM, MEV, LRS-074/B). The majority of the patients (41%) had entered the IV clinical stadium (Ann Arbor) with serious histological types of the disease (LDLL-45% and histiocytic 27%). This made us decide on LRS-074/B protocol (34%) and COP-BLAM cure (20%) planned for those with the advanced clinical stage and poor histological type of the disease. The full remission was achieved in 50%, partial in 28% of the cases while in 20% of the treated patients the therapy response lacked. Relapse of the disease occurs in about 50% of the treated patients. Patients treated with LRS-074/B protocol (p < 0.05) live statistically significantly longer. In a period of 24 months 50% of those treated with LRS-074/B protocol, COP and COP-BLAM cures show no symptoms. There is no a statistically significant difference regarding the mean survival rate (p > 0.05) in relation to the histological type of the disease.


[The effect of intermittent deep hypoxia on the adrenal gland cortex].

Wister laboratory rats were subjected to decreased atmospheric pressure occurring at the height of 23000 feet every day during 4 days and every second day during 11 days. The effect of hypoxia on the adrenal cortex and biochemical blood factors in rats, sacrificed at different times after the completion of exposure to hypoxic conditions was investigated. The hypoxic stress elicited alkalosis when Pa O2 and Pa CO2 were decreased, while the saturation oh hemoglobin by oxygen was enhanced. The animals, which were exposed to hypoxia for 4 consecutive days, better endured the whole course of the experiment than those ones exposed every second day. The histological changes in the adrenal cortex were stronger in the animals exposed to the experimental conditions with two-day breaks. The intensity, character and reversibility of the changes depended much more on the rhythm of exposure than on the rhythm of sacrifice.


[Typhoid fever--case report].

The paper describes a case treated at the Department of Infective Diseases in Novi Sad admitted during the remittance of typhoid fever. The course of the disease was atypical. Epidemiological and clinical features resembled those found in malaria but laboratory findings gave the true diagnosis. We found the case interesting because the diseased patient moved around a lot, making contacts with many people. Fortunately, contact diseases never happened to occur.


[Foreign bodies in the esophagus in children].

The study describes 3 children with strange foreign bodies in the esophagus, one aged 14 the other two 8 and 13 months respectively. A metal hanger hook was found in the first one, a lollypop with a plastic stick 10 cm long in the second and a painting brush 21 cm long in the third one. Two of the foreign bodies were removed ambulatory, the third one hospitally. The interventions were not followed by complications.


[Polycystic ovary disease: clinical picture, diagnosis and methods of therapy].

The study presents clinical features of polycystic ovaria with an incidence analysis of certain symptoms relevant for the diagnosis. Essential hormone parameters are showed, used for basal status evaluation, as well as endocrinologic tests applied for the determination of the causes of the disease within differential diagnostic investigation. Besides, in the differential diagnosis, possible diseases which should be excluded when diagnosing polycystic ovaria are showed. In the therapeutic protocol the stress is given to the methods used for the treatment of increased body hair, menstrual disorders and for ovulation induction. In the treatment of increased body hair cosmetic and medicamentous therapies are showed. In the ovulation induction method the application of clomiphene citrate, glycocorticosteroids, human menopausal genadotropins and a pulsatile pump for LHRH, have been analyzed in details. Moreover recent experiences in ovulation induction using LHRH analog (buserelin) and somatostatin analog (SMS) 201-995) are reported. Medicamentous ovulation induction was compared with surgical methods used for the induction (wedge resection and ovarial electrocauterization) pointing to the advantages and disadvantages of each method.


[The metabolic X syndrome--4 case reports].

The study reviews current knowledge about metabolic X syndrome characterized by android obesity, arterial hypertension, insulin resistance with hyperinsulinemia and disturbed carbohydrate tolerance, a decrease of HDL cholesterol and an increase of the triglyceride rich VLDL particle level. The study describes 4 female patients having been diagnosed for this syndrome. Only an ontime and vigorous reduction of overweight, along with intensified physical activity can prevent later development of serious complications, first of all, in cardiovascular system.


[Sudden sensorineural hearing loss of unknown origin].

The study presents the results of a ten year experience in the treatment of abrupt hearing loss of unknown etiology in 248 patients. More successful treatment was achieved in patients with lesser degree of perceptive hearing reduction and those showing no vestibular symptomatology. A decisive factor for a favourable hearing recovery is time between the onset of the disease and the beginning of the therapy. Having this in mind, the authors insist on early diagnosis and early administration of drugs affecting the inner ear perfusion.


[Malignant epilepsy in children: therapy with high doses of intravenous immunoglobulin].

22 children with intractable childhood epilepsy (ICE) showing no response to conventional drugs of hormone (ACTH, Synacten) therapy were administered i.v. immunoglobulin (ENDOBULIN immuno) at a dosage of 400 mg/kg on the first and 15th day and subsequently every 3 weeks for 6 months. 12/22 patients showed IgG2 subclass deficiency. A significant reduction in attacks, or even absence of attacks was observed in 13/22 children after 6 months of i.v. immunoglobulin therapy. Most of this children showed IgG2 subclass deficiency. The reduction of attacks after i.v. immunoglobulin therapy correlated with the improvement or normalization of the EEG finding. As for the psychomotor development, no major changes were noticed with respect to the condition prior to the therapy, but in children with IgG2 deficiency, there is no further psychomotor deterioration. 6 months after the last i.v. immunoglobulin dose positive therapeutic effect remained in 5/22 children, with 3 children the therapy was repeated because of recidive attacks and worse EEG findings, and proved effective. Light worsening of the EEG findings was found in 3/22 children, 2/22 dropped out, 1/22 child died of intercurrent infection, and in girl the attacks ceased entirely 4 months after the last i.v. immunoglobulin dose. With other children the condition remained unchanged. According to the authors opinion, i.v. immunoglobulin has its own place in ICE treatment, and it is evident in all cases where the classical antiepileptic and/or hormone therapy was unsuccessful, especially in children with IgG2 subclass deficiency, that is, in all the epilepsy cases where a great number of attacks is imperilling the psychomotor development in children, independently of type.


[The most common problems in differential diagnosis at the Outpatient Infectious Diseases Clinic in Novi Sad].

The most frequent differential diagnostic problems in the work of specialist for infective diseases were noticed and observed during several years at the out-patient clinic of the infective department. They are classified according to clinical syndromes. The most frequent are icterical, gastroenterocolitical, rash and meningeal syndromes, then follow lymphadenitis colli, anginas, status febrilis and pertussis syndrome. The aim of presentation is to point out the most frequent errors in physician's practice.


[Primary health care and corresponding health technology in clinical practice].

The aim of the study was to find out what general practitioners know and perform in the primary health care. The interview comprised 22% of all general practitioners from the region Novi Sad. The results obtained show that general practitioners have knowledge about definition, content of the work, about their role and what should be done according to the principles of the primary health care. But their knowledge, especially on methods of health education and methods of early diagnosis of risk factors and diseases are not fully applied during routine work. In order to achieve their role as a key persons for health strategy general practitioners must be educated for programme work, for intersectoral coordination, for monitoring and evaluation of the results of their work.


[Drug therapy of nocturnal enuresis].

Bed wetting is a disorder the origin of which different authors find in different etiopathogenetic mechanisms. Depending on the etiologic concept different therapeutic methods have been used. Treating bed wetting, authors claiming that the basic cause is a disorder in the integration of central vegetative functions and sleep, most frequently administer anticholinergic agents, making use of their marginal central anticholinergic effect and their impact on sleep phases. For children who wet in bed, having an urodynamic disorder and the disordered function of the pelvic floor musculature, effective drugs would be those with peripheral anticholinergic effects as well as pelvic floor musculature reeducation exercises. In conformity with the current understanding of the bed wetting etiology due to disordered Adiuretin excretion circadian rhythm, the applied drug is synthetic Adiuretin. It has been pointed out that bed wetting, being a heterogeneous group of disorders, should be etiologically classified by additional diagnostic methods, and that the treatment should include aimed etiological therapeutical methods.


[Risks for neonates born in the breech presentation].

A prospective study included 106 females and their newborns, 45 of them born in breech presentation and 61 delivered normally. The incidence of prepathologic and pathologic CTG records and meconial amniotic fluid is significant (0.01), more frequent in breech presentation (24.44% and 22.2%) than in normal deliveries (8.20% and 9.84%). Children born in breech presentation have significantly (p < 0.005) lower Apgar score values after the 1st and 5th minute than the control children. Infants born in breech presentation have significantly (p < 0.01) lower pH values (7.25 +/- 0.093) than those delivered normally (7.30 +/- 0.056). The acidosis incidence (pH < 7.20) in the studied group was 26.66% and 3.38% in the control group. In early neonatal period the disease occurred in 35.55% of the breech presentation group and 9.83% of the normal group (p < 0.01). In the control group there was no intracranial hemorrhages and manifest cerebral disfunction--complications most frequently involved in perinatal morbidity of children born in breech presentation (17.77% and 8.88%). One (2.22%) child born in breech presentation died in the early neonatal period.


A brief discussion of the development of Native owned health provider agencies in Alaska within the context of anticipated health and systems issues.

The Self-Determination Act brought about an explosive growth of tribally run programs in Alaska during the 1970s at the same time that the Alaska Native Claims Settlement Act was being implemented. Tribes demonstrated great creativity in blending IHS with other sources of funds to develop more effective and more acceptable delivery of services to their people. Further, the tribes in Alaska have demonstrated great aptitude in developing effective lobbying techniques with the United States Congress, such that they have actually been able to increase their funding base beyond what was assumed at the time of takeover from the IHS. However, several problems loom on the horizon. First, there is the problem of cost shifting within the IHS which contains the potential that tribes opting not to take advantage of the Self-Determination Act may be victimized by those who do. Second, there is the problem of too few resources to serve too many patients, which from time to time, propels the Indian Health Service toward an attempt to change the rules with respect to eligibility for services. Finally, the ability of the Indian Health Service (and by extension, its contract tribes) to provide an adequate level of services to American Indian and Alaska Native clients is being dramatically eroded by the same inflationary forces that are driving the larger system of health care in the United States toward the brink of disaster.


Health care in crisis: understanding nursing turnover in northern Canada (1).

For decades nurses have provided 24 hour comprehensive health care in isolated communities of Canada. As the only health care personnel in most communities of the north, nurses must meet all health care needs ranging from veterinary assistance to health education, emergency care to mental health counselling. This paper will focus on the structural and psychosocial factors affecting isolated post workers. Considering the intense nature of professional responsibility in these isolated settings, it is not surprising that there is frequent turnover of nurses. The constant change in staff results in poor community and staff morale, limited success of programs and increased expenditures for government due to the high costs of additional relief staff, travel, and orientation. Utilizing a mailed survey (N = 55) and on-site interviews (N = 17) collected in two regions of northern Canada, this paper will outline key issues which produce nursing dissatisfaction and ultimately decrease the effectiveness of health care programs. The paper will conclude with suggestions to increase nursing satisfaction and ultimately improve the provision of health care in northern areas. Native health care is in crisis. Health status indicators such as infant mortality and life expectancy lag far behind national statistics. Death due to accidents and violence are almost six times the Canadian rate. Incidence of suicide is three times the national statistics (1-6). The rate of nursing staff turnover in northern communities is high, and most nurses stay less than 2 years in the north (7,8). Native health demands are increasing and it is becoming more difficult for find nurses to provide health care service.(ABSTRACT TRUNCATED AT 250 WORDS)


Developing an integrated traditional/clinical health system in the Yukon.

The introductory steps have been taken in Yukon. Elders have met and voiced their concerns and initial contacts have been made with government officials, medical and legal consultants. A proposal is now being developed to obtain funding to design a suitable model for an integrated Yukon Indian/clinical health care system. One of the next steps, following on the advice of the Elders, should be for communities to establish their own projects to record the plants and practices used, with the assistance of their Elders. The communities should also identify people who use traditional practices who are willing to come forward. They could then come together with the Elders to discuss their concerns. Beyond that, representatives from the traditional system will need to meet with representatives of the mainstream system, to discuss areas of co-operation. Once the "content" has been identified, the model for integrating the two health systems can be addressed. This will necessitate further meetings of Yukon Territorial Government officials, legal advisors, medical advisors, and Yukon First Nations representatives. The proposal currently being developed will build on the initial steps which have been taken. The Yukon Territorial Government has indicated a willingness to look at ways of including traditional health care practices for patients who wish to use them. The receptivity of government and Yukon medical profession and the expressed concerns of the Elders indicate that now is the time to proceed.


Developing community mental health services for indigenous people of northern Ontario.

Inadequacies of three common models of mental health service delivery have been presented but each of these can contribute to an adequate system if the approach aims at the totality of mental health care. The key to service delivery and the provision of services in the local community by adequately trained and supervised mental health workers familiar with the culture and language and who are involved with other community workers in an inter-agency process. A major and the most important part of the work occurs in this level. This front line work must have the back-up and support of the system which has three roots. The clinical root is that of a support team of professionals, the local nursing station, hospital and the tertiary institutions. The second root is in training and education by recognized courses and other resources and the third in an adequate administration in which the indigenous population has been put in control.


Community crisis intervention in suicide epidemics.

The characteristics of "epidemic" suicides in native communities are discussed. It is hypothesized that the suicides are but one of many indicators of general community disorganization and problems. It is felt that concentration on the suicide problem although necessary, may detract from efforts at remedying the basic problems. Three communities are used to illustrate their "dynamics" and some principles of crisis intervention in such situations are presented.


Health attitudes and behaviours of Native Alaskans.

Health attitudes and behaviours were determined for residents of Western Alaska in a survey administered during the winter of 1988-89. One third of the villages in this region were randomly selected for inclusion in he study and one in three households in these villages were randomly selected to be interviewed. Bilingual interviewers successfully completed questionnaires for 477 households (77%). The vast majority of the sample population believed that a balanced diet, weight control, regular physical exercise, stress avoidance, regular medical attention and cessation of smoking and excessive drinking were important to health. Nevertheless 41% of respondents did not deny smoking, and 50% of these did not believe smoking cessation was important for health. Similarly, 34% of the population did not deny heavy drinking, and 38% of them did not think it was important to stop. When those who did not deny smoking were asked if they had tried to stop, 36% said they did not try. Of those who did not deny drinking heavily, 26% did not try to stop. Western Alaska has high rates of alcohol-related health problems and growing rates of tobacco-related diseases. The attitudes and behaviours with respect to alcohol and tobacco use exhibited in this study suggest a great need for health education and promotion activities directed at these habits.


Relationship between tuberculin reactivity and hepatitis B virus infection in the Northwest Territories.

Of 370 NWT Inuit or Dene who were HBsAg-positive, only 31 had HBeAg. Persons who were PPD negative were 6.2 times more likely to be HBeAg-positive than those who were PPD positive, but this inverse association applied only to those 30 years of age. We further analyzed a group of 3,378 Inuit whose status was known for HBV serologic markers and PPD reactivity. Overall, a significantly greater proportion (76.2%) of HBsAg positives were PPD reactive in comparison to those positive for anti-HBs (67.2%) or who had no HBV markers (43.2%). For persons 30 years of age who were positive for HBsAg or anti-HBs there was no significant difference between the proportions with PPD reactivity but a significantly smaller proportion of PPD reactivity was found in the no marker group. Among persons 30 years of age, the proportions of those who were PPD reactive were statistically equivalent across all three HBV marker groups. We conclude that patterns of HBV infection in NWT are random with respect to tuberculin reactivity resulting from either exposure to M. tuberculosis or administration of BCG vaccine.


A case of insect borne tularemia above the tree line.

A case of insect borne transmission of ulceroglandular tularemia in Canada above the tree line is presented. It seems likely from the available entomological data that a mosquito was the vector in this case. Mosquito vectors may be important in inducing the high seroprevalence of antibodies to F. tularensis above the treeline. This case is presented to make clinicians aware of the possibility of tularemia in cases of insect borne ulceroglandular disease in the arctic and, the necessity of measuring tularemia agglutinins in these patients. It should be noted that isolation of this organism poses a risk to laboratory personnel, and therefore should only be attempted in a reference laboratory. Therefore the diagnosis is based upon the finding, in the appropriate clinical context, of a four-fold rise in the tularemia agglutinins, or a single convalescent titre of 1:160 or greater.


Alcohol consumption and risk-factors for ischemic heart disease in Chuckchi inhabitants: clinical, biological and population studies.

Clinical, biochemical and epidemiological research has shown variations of serum enzymatic constellations (relatively high level of GGT in Chuckchi natives compared to nonnative newcomers). This difference leads to different unspecific body resistance to exogenous factors, particularly to histamine-liberators. The GGT system has also been linked to alcohol-induced clinical IHD. Based on these findings patients will be screened for GGT activity, which may serve as a marker for population phenotypes representative of high-risk groups. This deficiency in GGT may indicate a high risk for alcohol-related heart disease.


IHD in male population of Novosibirsk and Chukotka.

1. Syndrome of angina pectoris of effort is the most typical manifestation of IHD in native and newcoming population of the coastal part of Chukotka. 2. Ischemic ECG changes are less specific in relationship to IHD for Chukotka native population than in Chukotka newcoming and Novosibirsk populations.


Cancer patterns in the Inuit population of Canada 1970-1984.

1. Rates for lung cancer in Canadian Inuit are high and increasing for both men and women; in fact they are the highest reported rates for lung cancer among any Inuit population. 2. Cervical cancer in Canadian Inuit are high but rates appear to be stable, unlike the rapidly increasing trend reported in both Alaska and Greenland. 3. Rates for traditional Inuit cancers such as those of the nasopharynx and salivary gland do not appear to be declining in Canadian Inuit. 4. Rates for colorectal cancer in Canadian Inuit are similar to those expected for the Canadian population as a whole and do not appear to be increasing. 5. Finally, cancers traditionally reported to be rare in Inuit are still rare in the Canadian Inuit population; these include breast, prostate, bladder, and endometrial cancer. Cancer is a disease which can be controlled through prevention, early detection or treatment. The following future directions arising from this work reflect this paradigm. First, the Inuit cancer registry developed for this analysis will be used as a base for further research into environmental and genetic factors influencing cancer rates in the Inuit. Second, given that at least 40% of cancers in Canadian Inuit are cancers of the lung and cervix, health promotion programs should be developed to encourage tobacco-free environments to halt the epidemic of lung cancer, and also to make available Pap smear programs for early detection of cervical cancer. Third, health care services and programs, including diagnosis and treatment, should be culturally accessible to the Inuit population (6).(ABSTRACT TRUNCATED AT 250 WORDS)


Hereditary site-specific colon cancer in a Canadian kindred.

In summary, we have presented a large Canadian kindred exhibiting hereditary large bowel cancer, without polyposis coli, transmitted in an autosomal dominant fashion (Hereditary Site-Specific Colon Cancer). This series serves to emphasize the heritable nature of this and other malignant conditions and the importance of so fundamental a concept as the taking of a complete family history in the identification and management of these conditions. Looking to the future, the reduction of morbidity and mortality from Hereditary Site-Specific Colon Cancer lies in the education of the family and genetic counselling, both commencing in the mid teens the education of physicians and surgeons in the very considerable risk of malignancy in this condition the surveillance of asymptomatic family members including such measures as stool testing for occult blood six monthly augmented by air contrast barium enema and/or colonoscopy at two yearly intervals, commencing at age 25 the creation of national and international registries the identification of reliable biomarkers. We are indeed fortunate to live in a age when technology holds promise for the identification of the oncogenes operative in this and other heritable malignancies. This is the subject of ongoing collaboration between us and our molecular biology colleagues at Memorial University in St. John's and exemplifies, I believe, the very best in the cooperative spirit which may exist between a community hospital and a larger teaching centre.


Reaction of patients with effort angina to cold exposure during exercise.

An attempt has been made to characterize so-called "responders" to cold among patients with effort angina. Forty-nine such patients, unselected with regard to their history of reactions to cold, who showed ST depressions during and after exercise, were examined. They worked on a bicycle ergometer close to their maximum capacity, Wmax, at room temperature (about 23 degrees C) and in a cold room (-15 degrees C). ECG was recorded and a rating scale was used to estimate the perceived exertion during exercise (RPE). The presence of angina pectoris during exercise and its duration after exercise was recorded by an EA score. An EA/W index was used to estimate the severity of the effort angina. In the whole group, the mean Wmax decreased and the mean ST depressions, RPE, and EA/W index (but not EA score) increased on exposure to cold. The changes in these variables due to exposure to cold were all associated (but not the EA score). Criteria requiring a decrease in Wmax or increase in ST depression, RPE or EA/W index on cold exposure identified 53 to 63 percent of the patients. By combining the criteria, the number of patients, who were identified, decreased. If all the criteria were applied, about 30 percent of the patients were identified as "responders" to cold and they showed the most marked responses. Thus several exercise ECG test parameters may be used to reliably define "responders" to cold exposure. This may enhance future studies of the response reaction.


Pathophysiology of thermoregulation in patients with poikilothermia.

To investigate the thermoregulatory mechanisms underlying poikilothermia in man, we have studied 4 female patients (age 28-37 yr) with poikilothermia, most probably of hypothalamic origin, as well as 4 female volunteers of similar age. In a climatic chamber the participants were subjected to cold stress (16.5 degrees C) and subsequent heat exposure (40 degrees C). In the volunteers cold stress did not influence the rectal temperature; cooling induced a marked shivering response and an immediate peripheral vasoconstriction. Subsequent heat challenge induced a slight rise in the rectal temperature (from 36.3 +/- 0.2 to 37.0 +/- 0.3 degrees C) and a marked sweat secretion in all control subjects. All patients were hypothermic at the start of the experiment. Cooling induced a decrease in the rectal temperature of 0.3-0.9 degrees C. Three patients showed neither peripheral vasoconstriction nor a shivering response to cold stress. In contradistinction to the control subjects, in all patients an afterdrop of the rectal temperature of 0.3-0.5 degrees C was observed once heating of the environment had started; thereafter a progressive rise in core temperature occurred up to 38.5 (38.0) degrees C. In none of the patients sweat secretion was clinically visible. These results reveal that in these patients with poikilothermia the disorder of thermoregulation is accompanied by inadequate cutaneous vasomotor adjustment and disturbed sweat response and likely reduced metabolic response to cold stress.


Thermoregulation in man during cold adaptation.

Permanent residence in a cold environment affects the thermoregulatory system and other related functions (Table 5). These changes are adaptive because they decrease the stress action of cold, maintain the energy cost of temperature homeostasis and make it possible to receive additional heat during muscular work in cold without drawing on such heat production sources as shivering.


Cognitive and physiological feedback on cold pain tolerance.

Results supported the relevancy of cognitive information effects on pain tolerance, in that subjects who were given a rational and accurate explanation of what to expect showed greater tolerance than those who received irrelevant information. Accurate monitoring of hand temperature did not seem necessarily advantagous as an influence on pain tolerance. It appears merely watching a monitor, regardless of the specific contents of the screen, resulted in longer hand immersion times when compared to no monitor. The monitors seem to serve as distractors and specificity of physiological information was not particularly useful. However, neither information nor physiological monitoring emerged as the primary influence on pain tolerance in this study. Instead, the strongest predictors found were motivation and self-efficacy. The subject's own self prediction of anticipated performance with cold induced pain was closely consistent with actual performance. Although these results alone may not generalize to extended field situations, this study does reinforce the general findings of previous research: namely Bandura's (10) evidence on self-efficacy. While it is obvious cold temperatures have measurable physiological consequences, the experience of pain is also psychologically mediated. Pain associated with cold injury and frostbite in hospital studies show personality correlates are significantly related to the frequency, severity and tragedy of subsequent results (15). A replication of this study will include male subjects even though it is anticipated that findings will be consistent, with perhaps longer immersion times. Future research may want to develop training strategies aimed at teaching self-efficacy and realistic expectations of potential consequences in cold environments rather than scare tactics regarding physiological and psychological cold pain tolerance.


The role of hereditary factors in phenotypic variability of hormone levels in a population genetically adapted to the circumpolar environment.

The variability of plasma cortisol, T3, T4, TSH, and estradiol levels was studied in the North Khanty population genetically adapted to the extreme conditions of the North. Negative linear correlations of T3 and T4 levels with age were obtained. Cortisol, estradiol, and T3 levels showed nonlinear age dependency. T4 concentrations were significantly lower in August than February and November. The highest heritability estimate was shown for estradiol levels (44%). The relationships between genetic markers and hormone concentrations were studied.


Family violence in the north: what do we know and where do we go from here?

This paper has attempted to outline questions which should and should not be part of a Northern research agenda. There is, in my view, a large need for continued applied and evaluative research which will make a direct contribution to ending violence against women and children. Both researchers and funding bodies have a responsibility to ensure that limited resources are used wisely and, in particular, that the funding of any research project be contingent upon a clear demonstration of the direct and immediate relevance of the findings to the development and improvement of services.


Frustrations in delivering a dental service to the north coast of Labrador.

The delivery of a dental service to 4,000 people by 2-3 dentists, appears straight forward, in theory. It proves to be a different story in reality. Having prior knowledge of these problems, may be of help to dentists who wish to work here. One must experience the situation for oneself, however. There are certainly a "more than normal" amount of problems to confront on a daily basis. Accommodation and travel arrangements, seem to be the most pressing issues which need improvement. The usual work span of a dentist is between one and three years. The amount of work done by each dentist can vary on a daily basis. Native traditions can be such that, patients do not show up at the dental clinic until too late. Violence, suicides, and alcohol or solvent and drug abuse, as is being seen today, can "burn out" any health worker. Equipment needs to be upgraded in some of the Stations, like Hopedale and Davis Inlet. Salaries need revising.


A descriptive study of early caries and oral health habits of Inuit pre-schoolers: preliminary results.

Despite reports describing the high incidence of baby bottle tooth decay (BBTD) in North American native populations, very little is known about the factors influencing dental health at such an early age. Furthermore, true prevalence figures are usually difficult to obtain because few studies have attempted to survey the whole population. The purpose of this project is to determine the true prevalence of nursing caries in the Kativik region and describe oral health determinants in relation to the dental status of these children. At this time, 244 children aged two to five years have been surveyed. The results indicate that baby bottle tooth decay occur in 72.2% of this young population.


Nutrition of the Inuit: a brief overview.

Changing food preferences and health beliefs are resulting in a decline in use of traditional Inuit foods and an increase in use marketed foods. These changes are associated by many researchers with a variety of health concerns that currently are increasing among Inuit populations. Recent food composition studies have facilitated evaluation of dietary intakes of nutrients and organochlorine contaminants. In one Baffin Inuit community, traditional Inuit food species were found to still be a major component of women's diets, and to make a significantly greater contribution than marketed foods for certain nutrients; however on the annual average marketed foods contributed greater amounts of total dietary energy, fat and calcium. Vitamin A and calcium were found to be routinely below recommended amounts in women's diets. PCBs and toxaphene's were contained in the diet in fatty sea mammal tissues; however the average woman's diet, on the annual basis, contained less than one-third of the provisional tolerable levels of these organochlorine contaminants. The diets of the Inuit, as of all Indigenous People, are not comprised solely of the historically traditional foods; however these foods are still vitally important as a source of nutrients and cultural definition. The presence of industry-derived organochlorine contaminants in Inuit food species is yet another demonstration that action is needed on environmental protection by local, national and international agencies.


The importance of a functional communications system in the provision of health care in rural Alaska.

Paraprofessional health care workers in rural Alaska rely on an intact communication system for guidance in patient care and as a source of support for themselves in performing a difficult job. Though able to function without the system when necessary, the telephone reduces the crushing sense of responsibility and profound isolation experienced by CHAs as they struggle to meet the health care needs of their communities.


Nutrient intake among Saami people today compared with an old, traditional Saami diet.

The Saami diet consisted almost entirely of meat and fish in the past and has in general changed considerably during the twentieth century. The diet has become more like a western society diet with increased intake of carbohydrates, both as vegetables and fruits but also as sugar and a decreased intake of meat. These changes are confirmed in this dietary survey and the results reveals that the Saami diet today contains less protein and more carbohydrates and hence a lower phosphate/carbohydrate ratio than in the past. The old traditional diet contained high levels of nutrients such as zinc, phosphate, vitamin B12 and selenium due to high meat consumption. The todays Saami diet still contains more of these nutrients compared with the Swede's diet. The changes in food habits and nutrient intake, expressed in this study as nutrient density and nutrient ratios together with empirical statements in old documents are important to include in the discussion of diet, health and disease.


Benefit-risk considerations of traditional food use by the Sahtu (Hare) Dene/Metis of Fort Good Hope, N.W.T.

In summary, based on these preliminary data: a) traditional Dene foods make a substantial contribution to the adult RNI for protein, iron, and zinc; b) the Dene component of the diet is lower in total fat and has a higher P:S ratio than does the marketed component; and c) adults consuming a variety of Dene foods at the current average level of consumption during high traditional food use periods are not at risk of exceeding the provisional tolerable daily intake for PCBs. In conclusion, however unattainable "zero-risk" in food is, the fact remains that striving towards it is an important goal socially, physiologically, and ecologically. Managing risk on both global and individual levels is necessary.


Nutrition education for Native treatment centres.

Based on a needs assessment of native treatment centres and a pilot training project, a 10-day nutrition workshop was offered to 49 counsellors and cooks from 30 native treatment centres from six provinces. Objectives were to: 1) improve the understanding of the effect of alcohol on health and nutrition; 2) to improve the understanding of the role of nutrition in rehabilitation; 3) to clarify their respective roles and 4) to improve skills in menu planning for recovery and special diets, food safety procedures and cooking techniques appropriate for recovery. Assessment, counselling and treatment were considered in relation to native cultural values, meeting basic human needs and counselling theory. Participants rated the following at four or five (on a scale of one to five): meeting their expectations (98%); improving their understanding of the role of nutrition in total well being and recovery (98%); the effect of alcohol on health and nutrition (98%); the recovery diet (96%), special diets and planning and adapting menus (94%) and food safety (96%); developing skills in nutritional assessment (92%) and counselling (89%). Ninety-two percent were interested in further training and 94% of participants would recommend this training to others in the addiction field.


Dietary omega 3 fatty acids and gestational hypertension in the Inuit.

Blood pressure at the end of pregnancy and the incidence of pregnancy-induced hypertension were monitored in Inuit communities in the Keewatin region of the Northwest Territories. Communities with more fish and sea mammals in their diet had a lower blood pressure at the end of pregnancy and a lower incidence of gestational hypertension. The lower incidence of gestational hypertension was independent of other variables, including pregravida weight and parity. Cord blood phospholipid fatty acid analysis confirmed higher levels of eicosapentanoic acid, a fatty acid enriched in fish and sea mammals, in infants born to mothers from communities with higher fish in their diets.


A revised weight loss program in Manitoba Native communities.

In summary a culturally relevant weight loss program should consider the factors of age, education, economics and community. If these factors are not considered then it is the opinion of the author that programs involved with health may not succeed on a reserve.


Signal transduction pathways in keratinocytes.

Mammalian cells do not live as isolated organisms, but are instead organized into complex, highly specialized tissue organs composed of a homogeneous or a mixed cell population. In order to maintain tissue homeostasis in physiological and pathophysiological conditions, intercellular communication is an absolute requirement. This review will summarize our current knowledge as to how an extracellular signal is transduced via a specific receptor to the interior of the cell and how this signal will induce special cell functions. Attention will be paid to the major signal transduction pathways known to be active in keratinocytes, namely the adenylate cyclase, guanylate cyclase, tyrosine kinase, and phospholipase C systems. Finally, examples will be given of how interactions between these signal transduction pathways can take place and how 'signal cross-talk' might regulate keratinocyte function.


Isolation of plasma membranes from keratinocytes: a newly developed method allows the sensitive detection of the membrane antigen pattern in normal and psoriatic skin.

Distinct differences of proteins in the plasma membranes have been described in psoriatic keratinocytes as compared with normal epidermis. These changes are presumably involved in the pathogenesis of psoriasis. To identify and distinguish glycosylated proteins of the plasma membranes of keratinocytes, a method for mild preparation was developed that avoids the use of degrading or digestive enzymes. After cell lysis, three steps of centrifugation were performed, including the use of a sucrose step gradient. A fine-vesicular membrane fraction was obtained. Using marker enzymes for cell compartments, no contamination of cell nuclei or mitochondria and only 0.4% of endoplasmic reticulum was detectable in the final membrane fraction. Based on this preparation, disc-polyacrylamide-gel electrophoresis, followed by Western blotting, were performed. Staining with five different lectins to visualize glycosylated proteins allowed 75 different membrane glycoproteins to be distinguished. The patterns of normal, transformed (HaCaT), foreskin and psoriatic keratinocytes after cell culture with one passage were compared. Up to six proteins per lectin staining were expressed differently in psoriatic as compared to normal keratinocytes. Psoriatic cells shared similarities with highly proliferative foreskin cells, but not with transformed HaCaT cells. Main alterations of glycosylation were detected in the fucose content. In conclusion, the method developed for isolation of plasma membranes allows selective and sensitive examination of plasma membranes of normal and pathological keratinocytes. The glycosylation patterns observed suggest that distinct membrane proteins may be involved in the pathogenesis of psoriasis.


Induction of inflammatory cytokines in murine keratinocytes upon in vivo stimulation with contact sensitizers and tolerizing analogues.

In order to elucidate the role of keratinocytes (KCs) in the induction of contact sensitivity, we applied various contact sensitizers [2,4-dinitrofluorobenzene (DNFB), urushiol, 3-n-pentadecylcatechol (PDC), 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone)] and tolerizing compounds [2,4-dinitrothiocyanobenzene (DNTB), 5-methyl-3-n-pentadecyl-catechol (5-Me-PDC)] onto the earskin of non-sensitized Balb/c mice. In addition, we applied croton oil as a non-sensitizing, but stimulatory agent. Cytokine production was demonstrated by Northern blot hybridization of the total cellular RNA extracted from epidermal cells depleted by Langerhans cells and Thy 1+ dendritic cells using radiolabeled DNA probes encoding for the murine cytokines IL-1 alpha, -2, -3, -4, TNF alpha, IFN tau, GM-CSF and G-CSF. From all cytokines tested, TNF alpha and IL-1 alpha were markedly increased upon in vivo stimulation with contact sensitizers and also after application of croton oil. Both light and electron microscopic immunostaining with a polyclonal and monoclonal antibody demonstrated the presence of TNF alpha in the epidermis. This staining was most pronounced in KCs of the suprabasal epidermis upon application of contact sensitizers or croton oil, but not with tolerizing analogues. Using a functional assay significantly more TNF alpha was found in the supernatants of KCs treated in vitro with DNFB or LPS than with DNTB. GM-CSF was found in untreated epidermis as well as in stimulated cells. The results suggest that the sensitizing properties of contact sensitizers may partly be dependent on their ability to induce proinflammatory mediators. The induction and release of TNF alpha and IL-1 alpha in KCs by contact sensitizers may play an important role in the early response to immunogenic or inflammatory signals in vivo, whereby tolerance induction seems to be less dependent on these cytokines.


Pathogenesis of mechanobullous disorders.

Recent advances in the molecular biology of the dermo-epidermal basement membrane zone have contributed greatly to our understanding of the etiopathogenetic pathways underlying mechanobullous disorders. Genetic linkage was established between the keratin gene clusters and epidermolysis bullosa simplex, and keratin mutations were identified in several patients. Anchoring filaments and the alpha 6 beta 4 integrin are likely to be affected in junctional EB. Genetic linkage was established between the collagen VII gene and both dominant and recessive subtypes of dystrophic epidermolysis bullosa, and different molecular abnormalities of collagen VII leading to formation of non-functional, rudimentary anchoring fibrils were observed in several families. These discoveries that led to definition of mutations underlying EB also help us to understand the normal physiology and function of the affected structures. They may also point the way to new therapeutic strategies for common acquired blistering diseases and disturbances of epithelialization in general.


B-scanning evaluation with image analysis of psoriatic skin.

Ten psoriatic plaques from different subjects were investigated by 20 MHz ultrasound B scanning. Lesions were evaluated before therapy, and after 7 and 15 days of topical treatment with anthralin. Recordings from lesional skin were compared with those from clinically non-involved contralateral skin. Images were assessed by means of a new image analysis program, allowing the conversion of the B-scan image color scale into a numerical amplitude scale, the selection and highlighting of amplitude bands, and the quantification of objects reflecting in a definite amplitude range. B-scanning evaluation of the psoriatic plaque revealed a thickening of the epidermis and dermis, the presence of parallel acoustic shadows in the dermis, and a characteristic hypo-echogenic band corresponding to the papillary dermis. Image processing allowed an exact quantification of the progressive reduction in thickness of the epidermis and dermis and of the hypo-echogenic band observed at skin sites which had been treated with topical substances. Thus, the echographic method with image analysis allows the evaluation of three different parameters of response to topical treatment of psoriatic skin.


Spleen dendritic cells exhibit altered morphology and increased allostimulatory capacity after short-term culture.

Ia-bearing dendritic cells (DC) are a class of bone marrow-derived antigen-presenting cells that appear to possess an increased capacity to stimulate resting T lymphocytes. DC from different tissues share several morphologic, phenotypic and functional attributes. For example, freshly isolated DC from spleen resemble phenotypically and functionally freshly isolated Langerhans cells (LC) from epidermis; in addition, during short-term culture both DC and LC undergo several parallel changes including modifications affecting phenotype, capacity to present protein antigens, and ability to route surface Ia molecules into intracellular acidic compartments (J Immunol 1990: 145: 2820-2826). In the present study we show, using immunoelectron microscopy with anti-Ia and anti-33D1 monoclonal antibodies, freshly isolated DC in suspension to have a smooth cell surface with few and short cytoplasmic projections. By contrast, cultured DC display conspicuous bulbous cytoplasmic protrusions. In addition, spleen DC following culture for 24-48 hours exhibit an increased ability to stimulated allogeneic T lymphocytes in the primary mixed leukocyte reaction. These changes, similar to those described for freshly isolated and cultured LC respectively, further substantiate the close relationship between DC and LC.


Differential localization of ICAM-1 and HLA-DR expression on epidermal basal surface in mycosis fungoides and lichenoid reaction.

Scanning electron microscopy with immunogold labeling revealed that epidermal keratinocytes expressed ICAM-1 (intercellular adhesion molecule-1) and HLA-DR molecules on their surfaces in patterns that differed in mycosis fungoides (MF) and lichenoid reaction (LR). ICAM-1 molecules, visualized as deposits of gold particle, were visualized as clusters adjacent to the junctions interconnecting the keratinocytes of MF lesions. LFA-1 (leukocyte function-associated antigen-1) molecules were seen as granules on the surfaces of all infiltrates, most of which also expressed ICAM-1. HLA-DR molecules were seen continuously along the borders of the individual keratinocytes, thus producing a cobblestone appearance on the epidermal undersurface. In contrast, ICAM-1 and HLA-DR were found only sparsely on the undersurface of the epidermis from LR. These findings may help to explain the differing histological features of MF and LR: ICAM-1 molecules present on the intercellular junctions of MF epidermis lead the LFA-1-bearing cells to migrate into the interspaces, thus producing epidermotropism. These cells aggregate by means of co-expressed ICAM-1 to thus produce Pautrier's microabscess. In LR, the minimal expression of ICAm-1 on the epidermal undersurface leaves most infiltrates within the dermis, thus producing a band-like infiltrate.


Circulating immune complexes in patients with psoriasis: do they exist?

Sera from 16 patients suffering from active psoriasis without arthropathy (2 guttate, 10 nummular, and 4 mixed type) were examined for the presence of circulating immune complexes. Five routine laboratory assay systems were used, based on C1q-binding or detection of IgG-coupled C1q and C3-breakdown products. In 14 patients, no elevated levels of circulating immune complexes were detected. One patient, who additionally suffered from late-phase HIV-1 infection, showed C1q-binding activities as well as levels of IgG-coupled C1q and C3-breakdown products in four of the assay systems, which indicated the presence of immune complexes in his serum. In another patient, with nummular psoriasis, slightly elevated levels of circulating immune complexes were measured by two of the assay systems. These results question the hypothesis of an essential pathogenic role of circulating immune complexes in psoriasis.