Age-specific and compartment-dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons.

Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated with reduced cellular health. However, it is still unclear to what extent the decline of mitochondrial transport and function observed during ageing are coupled, and if somal and axonal mitochondria display compartment-specific features that make them more susceptible to the ageing process. It is also not known whether the biophysical state of the cytoplasm, thought to affect many cellular functions, changes with age to impact mitochondrial trafficking and homeostasis. Focusing on the mouse peripheral nervous system, we show that age-dependent decline in mitochondrial trafficking is accompanied by reduction of mitochondrial membrane potential and intramitochondrial viscosity, but not calcium buffering, in both somal and axonal mitochondria. Intriguingly, we observe a specific increase in cytoplasmic viscosity in the neuronal cell body, where mitochondria are most polarised, which correlates with decreased cytoplasmic diffusiveness. Increasing cytoplasmic crowding in the somatic compartment of DRG neurons grown in microfluidic chambers reduces mitochondrial axonal trafficking, suggesting a mechanistic link between the regulation of cytoplasmic viscosity and mitochondrial dynamics. Our work provides a reference for studying the relationship between neuronal mitochondrial homeostasis and the viscoelasticity of the cytoplasm in a compartment-dependent manner during ageing.

Assessing the specificity of the relationship between brain alpha oscillations and tonic pain.

Recent research proposed that the slowing of individual alpha frequency (IAF) could be an objective marker of pain. However, it is unclear whether this research can fully address the requirements of specificity and sensitivity of IAF to the pain experience. Here, we sought to develop a robust methodology for assessing the specificity of the relationship between alpha oscillations and acute tonic pain in healthy individuals. We recorded electroencephalography (EEG) of 36 volunteers during consecutive 5-minute sessions of painful hot water immersion, innocuous warm water immersion and aversive, non-painful auditory stimulus, matched by unpleasantness to the painful condition. Participants rated stimulus unpleasantness throughout each condition. We isolated two regions of the scalp displaying peak alpha activity across participants: centro-parietal (CP) and parieto-occipital (PO) ROI. In line with previous research our findings revealed decreased IAF during hot compared with warm stimulation, however the effect was not specific for pain as we found no difference between hot and sound in the CP ROI (compared to baseline). In contrast, the PO ROI reported the same pattern of differences, but their direction was opposite to the CP in that this ROI revealed faster frequency during hot condition than controls. Finally, we show that IAF in both ROIs did not mediate the relationship between the experimental manipulation and the affective experience. Altogether, these findings emphasize the importance of a robust methodological and analytical design to disclose the functional role of alpha oscillations during affective processing. Likewise, they suggest the absence of a causal role of IAF in the generation of acute pain experience in healthy individuals.

Visual cues of threat elicit greater steady-state electroencephalographic responses than visual reminders of death.

Terror management theory (TMT) suggests that reminders of death activate an exclusive anxiety mechanism different from the one activated by other types of symbolic threats. This notion is supported by evidence showing how experimental participants verbally reflecting on their own death are then influenced in their opinions and behaviours. A previous study showed that magnitude of electroencephalography (EEG) activity is greater when images depicting death-related content are coupled with painful thermal stimuli compared to threat-related content. Here we expand on previous research by testing whether similar effects may be brought about by passive observation of generic visual reminders of death. More precisely, we hypothesised that fast periodic presentation of death-related vs. more generic threat-related images determine a preferential modulation of brain activity measured by means of EEG. In two experiments, we found that images depicting death content elicit lower frequency-tagged EEG response compared to more generic threat images. Visual evoked potentials revealed that a brief change of the scene from neutral to threat content elicits greater amplitude at the late latencies (compatible with a P300 potential), particularly at the parieto-occipital sites. Altogether, our findings suggest that, in a context where no reflection on death cues is allowed and no threatening stimuli in other modality occur, visual death cues trigger lower neural synchronisation than that elicited by similarly negative and arousing cues with divergent threatening meaning.

[Two cases of malignant and benign systemic mastocytosis]. / Malignus és benignus systemás mastocytosis egy-egy esete.

The authors give a short account about the clinical histories of two patients: one with malignant systemic mastocytosis resulting in acute myeloid leukaemia, the other with indolent systemic mastocytosis. A brief review is reported about the physiological and pathophysiological role of mastocyte system. Benign and malignant types, classification of mastocyte proliferation are detailed, several distinct characteristics of clinical appearance, main aspects of diagnosis, therapy and prognosis in patients with different forms of systemic mastocytosis are briefly discussed.

[Molecular biologic study and the factor VIII gene in hemophilia A]. / A VIII. faktor génjének molekuláris biológiai vizsgálata haemophilia A megbetegedésben.

Results of inversion in the intron 22 region of the VIII factor gene studied by Southern blot are presented. Inversion was found in 20 of 46 patients. In 14 cases (70%) distal and in 6 cases (30%) proximal type of inversion was detected. The significance of the positive result in genetic counseling and in presymptomatic diagnosis of Haemophilia A is emphasized.

Cellular and humoral immune responses in haemophiliacs after vaccination against tick-borne encephalitis.

The primary immune response to a viral antigen (tick-borne encephalitis, TBE) has been determined in haemophiliacs. Twelve HIV-negative and four clinically asymptomatic, HIV-positive haemophiliacs as well as 16 age-matched healthy controls were included in the study. Antibody responses after TBE vaccination were comparable in HIV-negative haemophiliacs and controls; however, antibody titres in HIV-infected haemophiliacs were significantly lower after completion of the three-dose vaccination schedule (geometric mean reciprocal antibody titres (SEM): controls, 193 (1.37), HIV-positive haemophiliacs, 13 (2.18), P < 0.005). TBE vaccination failed to induce a T cell proliferative response in the HIV-positive haemophiliacs. While in HIV-negative patients the antigen-specific lymphoproliferative responses after primary and one booster vaccination were comparable to those of the controls, cellular responses were decreased in HIV-negative haemophiliacs following a second booster immunization 19 months after primary immunization (3H-thymidine incorporation, delta dpm, mean +/- SEM: controls, 34662 +/- 7129, HIV-negative haemophiliacs, 14339 +/- 7420, P < 0.005). As the protective mechanisms for TBE infection are not yet completely understood, further work will be necessary to determine whether the decreased capacity to mount a sufficient long-term cellular memory response in HIV-negative haemophiliacs might be important for the protective effect of TBE vaccination in this population.

[Primary (B-cell) mediastinal lymphoma]. / Primer (B-sejtes) mediastinalis lymphoma.

The authors present two cases of a new pathological entity--primary (B-cell) mediastinal lymphoma. The disease both clinically and histologically differ from the known lymphomas. Its diagnosis is possible only with the use of immunhistochemical methods. The low age incidence, the unusual course and the bad prognosis of the disease merits its publication.

[Results of multicenter treatment of highly malignant non-Hodgkin's lymphomas]. / Kifejezett malignitású nem Hodgkin-lymphomák multicentrikus kezelésének eredményei.

One hundred and eleven consecutive patients with highgrade non-Hodgkin's lymphoma treated in three centres between 1983 and 1988 were analysed to assess the efficacy of different types of chemotherapy. The median age at presentation was 56.9 +/- 16.6 years. According to the Kiel classification histological subtypes were: centroblastoma (n = 45), immunoblastoma (n = 17), lymphoblastoma (n = 6), T cell lymphoblastoma (n = 9), histiocytoma (n = 2), and high grade unclassified (n = 32). Patients were clinically staged, 68 patients (61%) belong to stage I-II. and 43 had widespread disease (stage III-IV.). Remission was achieved in 81 cases [70 complete (CR) and 11 partial (PR) remission], 30 patients did not respond. The most effective modality of treatment was extended field irradiation completed with chemotherapy (81% CR, 7-year overall survival 65%) followed by ProMACE-COPP chemotherapy (67% CR, 4-year survival 40%) and CHOP-Bleo chemotherapy (65% CR, 7-year survival 25%). Age and histological subtype had no prognostic relevance, whereas clinical stage proved to have significant influence on remission and survival.

[Experiences with a new second-line protocol in the treatment of pretreated and advanced Hodgkin disease]. / Erfahrungen mit einem neuen "Second-line-Protocoll" bei der Behandlung des vorbehandelten und fortgeschrittenen Morbus Hodgkin.

Between 1983 and 1987, we treated 16 patients with Hodgkin's disease, according to a post-COPP and a post-ABVD protocol, respectively. All patients had received previous treatment, including megavoltage cobalt radiotherapy, and were in advanced stages of disease, mostly with immunosuppression/immune deficiency. The protocol of lomustine, etoposide, adriamycin, methotrexate and prednisolone was commenced after the above therapy had failed or was not tolerated. Compared to the previously used chemotherapy, the 3 new cytotoxic agents were well tolerated. A complete remission was obtained in 4 patients and a partial remission in 9. In 2 patients, there was a temporary partial remission only. In more than half the patients, a positive effect on the clinical course was recorded. Viewed as a whole, a favourable objective and subjective result ensued. This LEAMP second-line protocol was found to be effective and well tolerated.

Genetic-epidemiologic study of haemophilia A and B in Hungary.

All known surviving haemophiliacs A and B and their relatives were reexamined by laboratory and clinical methods and evaluated by a genetic-epidemiologic approach in 4 north-western countries of Hungary. The prevalence of haemophilia A and B patients born in the fifties was 2.73 and 0.25 per 10,000 persons, respectively. The reproductive fitness was found to be 0.3 in haemophilia A, and 0.8 in haemophilia B patients. The mutation rates calculated by the indirect method were 6.3 x 10(-5) for haemophilia A and 0.2 x 10(-5) for haemophilia B.

Comprehensive epidemiological and clinicopathological survey of Hodgkin's disease in Hungary.

To determine the epidemiological pattern and some clinicopathological features of Hodgkin's disease in Hungary, the data of 233 consecutive patients with the disease from seven counties, diagnosed between January 1983 and July 1987, were analysed on the basis of data from four cancer centers. Large variations were noted in incidence rates between the different regions of Hungary. The epidemiological pattern seems to vary from those reported in developed and developing countries. A sharp rise in the incidence of Hodgkin's disease occurred at the end of the second decade of patients' lives. More of our Hodgkin's patients are at advanced clinical stages, with systemic symptoms and a histological type of mixed cellularity, at the time of diagnosis, than in the western hemisphere. On the average, there is a 6-month period between the appearance of the first sign or symptom and the diagnosis. There is a lack of data outlining the epidemiological differences in the pattern of Central Europa. The aim of this study is to supply data for the etiopathogenetic research of Hodgkin's disease, as there is an important task to improve the unfavourable home situation, and to strive for earlier diagnosis in this disease.

[Experience with a new "reserve protocol" in advanced and pretreated Hodgkin's disease]. / Uj "tartalék prótokollal" szerzett tapasztalatok elörehaladot és eläokezelt Hodgkin-kórban.

Between 1983-1987 16 patients with advanced stage Hodgkin disease, most of whom in an immunsuppressed, immundeficient state, were treated with a new "post-COPP", or "post-ABVD" reserve-protocol. In all cases megavoltage Co radiotherapy and COPP (CVPP) or ABVD polychemotherapy had previously been. Compared with the previously administered polychemotherapy the new 3-component cytostatic agent was well tolerated by the patients. The LEAMP-protocol therapy is therefore recommended in cases of ineffective combined radiochemotherapy (chemoresistance) or intolerance to chemotherapy. In four cases prolonged, complete, in nine cases partial remission was achieved and in more than a half of the patients favourable clinical effects and changes were experienced. In two cases temporary, partial remission was seen. One cases, because of the short period of treatment could not be evaluated. On the basis of the longitudinal observations the results achieved seemed subjectively and objectively favourable. The LEAMP-protocol was found to be well tolerated and satisfactorily effective.

[Experience with Cefobid in severe infections complicating immunodeficiency diseases]. / Cefobiddal szerzett tapasztalatok immundeficiens haematologiai betegek súlyos fertözéseiben.

As a 3rd generation cephalosporin Cefobid monotherapy was applied during 1985-1986 with 16 hematological patients in immunodeficient, immunosuppressive states where the available aimed and combined antibiotic therapy failed to be effective for the treatment of bacterial infections of grave course and septic character. 4 g/day was the average I.V. dose of Cefobid, higher doses were applied only in especially grave septic states. The hematological patients tolerated well the Cefobid in monotherapy. Recovery form the septic state and excellent clinical effect was found with 9 patients, good effect with 4 and satisfactory effect with 1 patient. In 1 case the therapy had to be stopped owing to drug hypersensitivity. Cefobid is regarded as an antibiotic drug that is effective if used in monotherapy for treating grave, septic infections of hematological patients in immunodeficient--immunosuppressive--myelodepressive states having received earlier antineoplasmic polychemotherapy.

[Onset of Philadelphia chromosome negative chronic myeloid leukemia with symptoms of intrahepatic cholestasis]. / Intrahepatikus cholostasis tüneteivel kezdödö Philadelphia chromosoma negatív chronikus myeloid leukaemia.

The case of a chronic myelogenous leukemia (CML) starting in an unusual form in a young woman is reported. Rapidly progressing icterus was the first and leading symptom of the disease. Simultaneously with the exclusion of the possibility of hepatitis and extrahepatic obstruction of the bile duct the qualitative blood picture roused the suspicion of a myeloproliferative disease. Detailed hematological examinations confirmed Philadelphia chromosome (Ph1) negative CML. Besides the histologically diffuse leukemic infiltration intrahepatic cholostasis could be demonstrated in the background of the icterus. In the chronic and accelerated phase clinical symptoms developing as a consequence of hepatic organic manifestation were dominating. In the authors's case the moderate leukocytosis, initial thrombocytopenia, absence of splenomegaly, early blast-phase and short survival were atypical, characteristic of Ph1 negative CML. The diagnosis and the absence of other associated hepatopathies was supported also by the post-mortem examination. CML beginning with icteric symptoms due to intrahepatic cholostasis is considered as rarity in the literature.

[Comprehensive epidemiologic and clinico-pathologic study of Hodgkin's disease]. / Reprezentatív epidemiológiai és klinikopatológiai felmérés Hodgkin-kórban.

To determine the epidemiologic pattern and some clinicopathologic features of Hodgkin's disease (HD) in Hungary, the data of 233 consecutive patients with HD, diagnosed between January 1983 and July 1987 from seven county were analysed on the basis of data from 4 cancer centers. Large variations have shown in incidence rates within different regions of Hungary. The epidemiologic pattern seems to vary from those reported in developed and developing countries. A sharp rise in HD incidence occurs already at the end of second decade. More Hodgkin's patients have advanced clinical stages, systemic symptoms, mixed cellularity histologic type at the time of diagnosis than in Western hemisphere. On the average, there is a six months period between the appearance of the first sign or symptom and the diagnosis. There is a lack of data outlining the epidemiologic difference in the pattern of Central Europe. The aim of this study was to supply data for the etiopathogenetic research of HD. There is an important task to improve the unfavourable home situation, to strive to earlier diagnosis in HD.

First occurrence of Hb H in Hungary.

Blood sample from a 52 year old woman of mild anaemia was investigated for thalassaemia. Based on the haematological data and the results of the restriction enzyme analysis we concluded that the patient was heterozygote for alpha-thal-1 and alpha-thal-2.

[The role of splenectomy in the treatment of lymphomas of low malignancy]. / Die Rolle der Splenektomie in der Behandlung von Lymphomen niedriger Malignität.

The effect of splenectomy was studied in 30 patients with non-Hodgkin lymphoma of low malignancy. Severe bacterial infections occurred in 9 patients. Follow-up of the total group of 72 patients-years revealed one infection requiring hospitalization per eight patient-years. With chronic lymphatic leukaemia there was no difference in the incidence of severe infection between splenectomized and non-splenectomized patients. In 12 patients the splenectomy produced favourable results in that in some (8) cytostatic treatment was no longer required, while in others (4) the dose of cytostatic drugs could be reduced after several months without any medication. Survival rate was not influenced by splenectomy.