Impaired monocyte activation in schizophrenia: ultrastructural abnormalities and increased IL-1ß production.

Monocyte activation is consistently reported in patients with schizophrenia (SZ). We aimed to study the ultrastructure of monocytes and monocyte production of IL-1ß in drug-free patients with SZ and controls. Monocytes from young (18-30 y.o.) healthy and SZ men in relapse were studied. Electron microscopy and morphometry were applied to estimate areas of monocytes, volume density (Vv), areas, and number of organelles. The production IL-1ß by monocytes was estimated by the ELISA method. Group differences were examined using ANCOVA. Pearson's correlation coefficients were used to examine the effects of possible confounding variables. Correlation analyses were applied to detect the relationships between the parameters of monocytes measured and between the parameters measured and the IL-1ß production. Area of nucleolus, Vv and area of mitochondria and lysosomes, and the number of lysosomes were significantly increased in patients as compared to controls. Area of mitochondria was correlated significantly with Vv and area of lysosomes, and the number of lysosomes was significantly correlated with area of monocyte and Vv of vacuoles only in the control group. The production of IL-1ß by monocytes was higher in patients than in controls (p = 0.01) and was correlated with Vv of lysosomes (r = 0.68, p = 0.04) and area of lysosomes (r = 0.78, p = 0.013). The data provide new evidence for over activation of monocytes in SZ and disturbed metabolic relationships between lysosomes, mitochondria, and vacuoles.

[Ultrastructural changes of lymphocytes in patients with schizophrenia treated with olanzapine]. / Ul'trastrukturnye izmeneniya limfotsitov u bol'nykh shizofreniei pri lechenii olanzapinom.

OBJECTIVE: to study the effect of olanzapine on the ultrastructure of different populations of lymphocytes and lymphoblasts in patients with schizophrenia. MATERIAL AND METHODS: Authors performed a morphometric study using electron microscopy of lymphocytes in 56 patients with schizophrenia treated for 8 weeks with olanzapine and 49 patients treated for 28 weeks with olanzapine before and after treatment. Authors estimated the frequency and ultrastructural parameters of small, large, large activated lymphocytes and lymphoblasts. RESULTS: The frequency of small lymphocytes in patients treated with olanzapine increased and that of large lymphocytes decreased in treated patients as compared to the patients before treatment. The volume fraction of lysosomes increased significantly in small, large and large activated lymphocytes after treatment as compared to the patients before treatment. CONCLUSION: The increased lysosome content in different lymphocyte subpopulations might contribute to the mechanism of olanzapine efficacy.

[Ultrastructural changes in platelets and their relationship with serotonin metabolism in patients with schizophrenia treated with olanzapine].

An aim of the study was to investigate the effect of olanzapine treatment on platelet ultrastructure and to search for its association with serotonin metabolism in patients with schizophrenia. Platelets of 59 patients with chronic (attack-like schizophrenia) treated with olanzapine and 31 health people were explored. Based on the data on the platelet ultrastructure, authors studied the content of functionally activated vacuolated platelets (VP) and less active granular platelets (GP) as well of platelet serotonin (PS). VP content was higher in patients compared to the control group (+57%, p<0.001). After treatment for 8 and 28 weeks with olanzapine, it decreased and reached the control level (52% and 57%, respectively). There were significant negative correlations between % VP and PS before treatment (r= -0.30, p=0.02) and 8 week after treatment (r= -0.29, p<0.04) and a positive correlation between the decrease in % VP and increase in the PS levels during 8-week treatment (r=0.34, p=0.008). The association between increased platelet vacuolization and decreased PS content in schizophrenia was demonstrated for the first time. This association disappeared after treatment that led to the normalization of % VP and PS levels.

[Ultrastructural changes in platelets of schizophrenia patients: a link with serotonin metabolism and therapeutic efficacy].

OBJECTIVE: To investigate the effect of olanzapine treatment on the ultrastructure of granulated platelets (GP) and vacuolated platelets (VP) and to find their association with platelet serotonin (PS) content and treatment efficacy in patients with schizophrenia. MATERIALS AND METHODS: Platelets of 49 patients with attack-like schizophrenia treated with olanzapine and 31 healthy people were explored. Electron microscopic morphometry of GP and VP was performed to estimate the ultrastructural parameters of platelets. Microfluorimetry was used to measure PS content. RESULTS; The number of pseudopodies in GP and VP were lower after 28 weeks with olanzapine (-13%, p<0.01) as compared to the patients before treatment but the mean platelet area was not changed. Vv of granules was reduced in VP after 8 and 28 weeks of olanzapine (-13%, p<0,05). Vv of vacuoles was increased in GP in 28 weeks with olanzapine vs. 8 weeks with olanzapine (+16%, p<0.01) and in VP in 28 weeks of treatment vs.patients before treatment (+13%, p<0.01). In patients before treatment, Vv of vacuoles in VP was significantly higher in nonresponders as compared to the responders (+11%, p<0.05) and significantly correlated with PS content (r=0.26, p=0.04). The association between the number and Vv of vacuoles in VP before treatment and time point for positive treatment effect was found for the first time. CONCLUSION: Ultrastructural changes in Vv of vacuoles in platelets of schizophrenia patients treated with olanzapine are associated with serotonin metabolism and therapeutic efficacy.

[An electron microscopic study of typical lymphocytes and atypical cells of peripheral blood in patients with schizophrenia].

An electron microscopic analysis of a lymphocyte population from peripheral blood of 120 patients with schizophrenia (60 patients with acute and 60 with chronic form) and 31 healthy people has been conducted. The ultrastructure and percentage of 6 morphofunctional cell types are described. A statistical analysis of the data revealed that patients with chronic schizophrenia had the substantially increased content of activated lymphocytes, in particular lymphoblasts, while patients with acute schizophrenia had the ameliorated content of activated lymphocytes along with the increased number of lymphoblasts. The high content of lymphoblasts is believed to be a characteristic feature of patients with schizophrenia (this type of cells belongs to so-called atypical lymphocytes described earlier). The atypical cells include also destructive lymphocytes, phagocyting monocytes and phagocyting neutrophiles. These atypical cells are observed more often in patients with acute schizophrenia. It has been suggested that the presence of an increased number of lymphoblasts in the blood of schizophrenic patients indicates the constant production of antigens and the presence of phagocyting cells reflects the processes of antigen neutralization.

[The ultrastructure of dark and light thrombocytes]. / Ul'trastruktura temnykh i svetlykh trombotsitov.

Ultrastructure of thrombocytes with dark, light and intermediate hyaloplasm density has been studied in a population of thrombocytes of human peripheral blood. Excretion of specific granules, development of vacuolar structure, the increase in contact activity, and the cytochemical activity of phosphohydrolythic enzymes is accompanied by the corresponding decrease in the hyaloplasm density. Dark thrombocytes may be considered as potentially active ones, and the light ones, as actively functioning thrombocytes.

[An ultrastructural and ultracytochemical study of peripheral blood thrombocytes in women with habitual spontaneous abortion]. / Ul'trastrukturnoe i ul'tratsitokhimicheskoe issledovanie trombotsitov perifericheskoi krovi zhenshchin s privychnym nevynashivaniem beremennosti.

An ultrastructural and ultracytochemical analysis of platelets was performed to assess the activity of 5'-AMPase and ATPase using a leukoconcentrate of the peripheral blood cells of non-pregnant women suffering from recurrent spontaneous abortion. The blood platelet populations were found to have increased proportions of light thrombocytes in phases I and II of the menstrual cycle, which was associated with pronounced ultrastructural and cytochemical signs of a release reaction showing their activated state: reduced density of the hyaloplasm, diminished quantity of specific and glycogen granules, development of the vacuolar system, 5'-AMPase and ATPase activity on the plasmalemma, light hyaloplasm, and in released specific granules and vacuoles. The release reaction is associated with a high contact activity of platelets which results in the formation of small and large platelet aggregates and attachment of other blood cells--erythrocytes, lymphocytes, and granulocytes. The intercellular fluid contains membrane fragments of destructive cells, including platelets with 5'-AMPase and ATPase activities, which may result in thromboplastin formation.

[Ultracytochemical detection of nucleoside phosphatase activity in human peripheral blood cells]. / Ul'tratsitokhimicheskoe vyiavlenie nukleozidfosfataznoi aktivnosti v kletkakh perifericheskoi krovi cheloveka.

The authors elaborated and described the optimum conditions for fixation, incubation and preparation of human blood cell samples in minimum quantities for ultrastructural and ultracytochemical investigations of 5'-nucleotidase and ATPase activities. The best preservation of the blood cell ultrastructure was obtained after fixation with buffered 1% glutaraldehyde solution followed by postfixation in buffered 1% OsO4 solution. The best ultracytochemical demonstration of 5'-nucleotidase and ATPase activities was achieved after fixation in buffered 2% formaldehyde prior to cytochemical incubation. DMSO added to either fixation or incubation media was shown to damage the plasmalemma and glycocalyx structure in cell suspensions. ATPase in 5'-nucleotidase activities were revealed in plasmalemma, cytoplasmic reticulum, Golgi complex, mitochondria and in the nuclei, in particular, in the perinuclear space, nucleolus and chromatin. With respect to the localization and activity of nucleosidephosphatases, lymphocytes proved to be most heterogenic, with the enzyme activity level directly depending on the rate of ultrastructural differentiation in lymphocytes.

[Electron microscope study of the changes in the pyriform neurocytes in the mouse cerebellum during protein-calorie deficiency]. / Elektronno-mikroskopicheskoe issledovanie izmenenii grushevidnykh nevrotsitov mozzhechka myshei, razvivaiushchikhsia v usloviiakh belkovo-énergeticheskoi nedostatochnosti.

The changes in the distribution of dark, light and intermediate pyriform neurocytes (Purkinje's cells) in the cerebellum of mice which developed under the conditions of protein-caloric deficiency were assayed from the 10th to the 40th day of mouse life. In the control animals, the number of dark cells was 7 +/- 3%, of intermediate 44 +/- 7%, and that of light ones 49 +/- 7%. Under malnutrition the number of dark cells rose to 26 +/- 5% (P less than 0.01), that of intermediate cells fell to 33 +/- 6% (P less than 0.01), and the number of light cells changed insignificantly (41 +/- 6%, P less than 0.1). Electron microscopy of the ultrastructure of dark cells has disclosed dystrophic and destructive changes in the nucleus and in the main organelles of the cytoplasm. Pronounced astroglial reaction was not infrequently observed around dark cells.

[Lymphocyte reaction in schizophrenia patients to the phytomitogens, concanavalin and phytohemagglutinin]. / Reaktsiia limfotsitov bol'nykh shizofreniei na fitomitogeny----konkanavalin i fitogemaggliutinin.

The capability of the schizophrenic patients' lymphocytes and lymphocytes of healthy persons to respond to the stimulating action of T-mutagens -- concanavalin A and PHA -- was studied. The T-cell count was determined by the method of rosette formation; the influence of adhesive cells on the lymphocyte response to mitogens was ascertained. The response to both the mitogens in the patients' lymphocyte cultures was reduced as compared to control, and the T-cell count failed to differ from the normal. The removal of adhesive lymphocytes results in the disappearance of differences between the response of the patients' lymphocytes and normal lymphocytes to both the mitogens.

[Electron microscopic study of the interaction between lymphocytes of schizophrenic patients and human embryo brain cells under tissue culture conditions]. / Elektronno-mikroskopicheskoe issledovanie vzaimodeistviia mezhdu limfotsitami bol'nykh shizofreniei i kletkami mozga émbrionov cheloveka v usloviiakh kul'tury tkani.

The authors convened an electron microscopic study of the interaction of lymphocytes in the peripheral blood of schizophrenic patients with the brain cells of the embryo after a 24-hour joint cell incubation. It was found that in comparison with the lymphocytes of the normals, the lymphocytes of schizophrenic patients much more frequently come into contact with the cells of the brain culture. The lymphocytes of the patients are characterized by an increased amount of cytoplasmatic processes. A maximum amount of lymphocytes which came into contact was seen in experiments on population enriched in activized cells of the lymphocyte in schizophrenic patients. It is particularly the activized lymphocytes of schizophrenic patients that coming into contact called forth degenerative changes in the cells of brain culture in the area of contacts.

[Adhesive lymphocytes in the peripheral blood of schizophrenic patients]. / Adgezivnye limfotsity v perifericheskoi krovi bol'nykh shizofreniei.

The blood of schizophrenic patients compared to that of normals contain 3, 4 times more adhesive lymphocytes. A blood analysis of 59 schizophrenic patients demonstrated that approximately 60% of the patients have a high content of such cells. Among the adhesive lymphocytes there are 5 times more activated, 3 times more wide plasmatic, but twice less narrow plasmatic lymphocytes compared to normals. According to the indices of adhesivity and according to ultrastructure signs it was found that the lymphocytes of schizophrenic patients react weaker to PHA than the lymphocytes of normals. It is assumed that the blood of schizophrenic patients contains biologically active substances, which bring on an increase of adhesive properties in the lymphocytes and their physiological activation.

[Effect of schizophrenic patients' serum on the physiological state of lymphocytes under in vitro conditions]. / Deistvie syvorotki bol'nykh shizofreniei na fiziologicheskoe sostoianie limfotsitov v usloviiakh in vitro.

The report is concerned with the action of the serum of schizophrenic patients on the physiological state of lymphocytes in normal donors. It was established that during the early stages of incubation the action of the serum in schizophrenic patients evokes the activation of lymphocytes in normal donors, that is seen in changes of the ultrastructure and adhesive properties of these cells. On the late stages of cultivation the serum of patients destroys 13.4 +/- 5.9% of lymphocytes of normal donors. In remaining population 21% of lymphocytes lose their capability to react to PHA stimulation by an increase of DNA content.

[Ultrastructure of schizophrenic patients' lymph nodes]. / Ul'trastruktura limfaticheskikh uzlov bol'nykh shizofreniei

By means of the electron microscopic method it became possible to study the structure of the lymph groin node (bioptic material) in 4 cases of schizophrenia and in 2 normals. All the schizophrenic patients had continuous forms (nuclear) of the disease, while their mental state during the period of examination was characterized as terminal. An analysis of the cell structure in the lymph node demonstrated that in both groups the functional activity of the lymphoid tissue was sufficiently high and in relation to some indices this activity was even higher in the group of schizophrenics (a more expressed pynocytose activity of the reticular cells and macrophages, a higher amount of blast forms of the lymphocytes, plasmatic cells and activated lymphocytes). The authors stress that these data are purely preliminary.

[Quantitative electron-microscopic analysis of the lymphocyte population in the peripheral blood of schizophrenic patients]. / Kolichestvennyi élektronno-mikroskopicheskii analiz populiatsii limfotsitov perifericheskoi krovi bol'nykh shizofreniei

The author conducted a quantitative submicroscopic analysis of a population of recently isolated lymphocytes in the peripheral blood of schizophrenic patients. At the basis of the analysis there lies a subdivision of lymphocytes into 3 types according to their ultrastructure: narrow-plasmatic (I), widerplasmatic (II) and activated (III) cells. In the blood of schizophrenic patients the correlations of these cells were 54%, 24% and 22%, while the same figures for normals were 63%, 24% and 13%. These data may indicate that in schizophrenia the peripheral blood contains 1.7 times more activated lymphocytes than in normals. The activated lymphocytes possess an increased adhesiveness. They probably are atypical lymphocytes in the peripheral blood of schizophrenic patients which can be seen through an optical microscope.