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Biomedical subjects

M Richter

Publications and source records attributed to M Richter.

At least 343 records · Page 19Linked to original sources

Lymphocyte studies in rheumatoid arthritis. V. Suppressor cell function in peripheral blood.

Peripheral blood lymphocytes from 30 patients with rheumatoid arthritis and 14 controls were examined for suppressor activity by two different assays. These were the Concanavalin-A-induced and the short-lived suppressor cell assays. There was no difference in suppressor activity between patients and controls, the suppressor activity of HLA-DR3 positive patients was no less than that of non-DR3 patients. However, patients with nodules showed reduced suppression in the short-lived suppressor cell assay when compared with patients without nodules.

Adult↗

[Experimental studies on the diffusion of antifibrinolytic agents in fibrin thrombi. A contribution to intrathecal antifibrinolytic therapy in subarachnoid hemorrhages].

The diffusion behaviour and the diffusion coefficients of antifibrinolytics in fibrin thrombi were determined by in vitro incubating attempts with tritium marked compounds of PAMBA, AMCA, and ECA as well as by chromogenic substrate determination for contrykal. The great diffusion ability of PAMBA supports the usefulness of intrathecal therapy of subarachnoidal bleeding for blocking endogenous fibrinolysis, whereas the exogenous fibrinolysis of the fibrin thrombus closing aneurysm is inhibited by the intrathecal application.

4-Aminobenzoic Acid↗

[Pharmacokinetic studies with 3H-labelled synthetic antifibrinolytics].

In rabbits and rats pharmacokinetic studies on the anti-fibrinolytics 4-aminomethylbenzoic acid (PAMBA), trans-4-aminomethylcyclohexane-1-carboxylic acid (AMCA), and epsilon-aminocaproic acid (EACA) were carried out using the tritium labelled compounds. Following i. v. administration of PAMBA and EACA in rabbits a two-phasic plasma level and following AMCA a three-phasic plasma level was found within 7 h. The rate constants beta of 0.34 h-1, 0.44 h-1, and 1.08 h-1 for EACA, PAMBA, and AMCA, respectively, indicate a more rapid elimination of AMCA. Accordingly, the AUC-values for AMCA are considerably smaller than those for EACA and PAMBA after both i. v. and p. o. administration.

4-Aminobenzoic Acid↗

[Animal experiments on the pharmacokinetics of N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP), a new thrombin inhibitor].

The pharmacokinetics of the synthetic thrombin inhibitor N alpha-tosyl-(3-amidinophenyl)alanine piperidide (TAPAP) was studied in rabbits using 3H-TAPAP. Concentrations in plasma, bile, urine and organs were determined by liquid scintillation counting. In plasma, moreover, the content of biologically active compound was measured by means of plasma thrombin-time determinations. After i.v. administration of doses of 1-10 mg TAPAP/kg a biphasic course of the plasma level resulted, the second phase of which has a half-time of about 5 h. This phase is considered to represent the elimination of a metabolite of TAPAP which no longer inhibits thrombin. The enteral absorption was incomplete after oral administration. Binding to plasma proteins amounted to about 50%. There was no preferential accumulation in organs or tissues. The bile contained relatively high levels of radioactivity in all routes of administration and doses studied. Elimination of TAPAP or of labelled metabolites is assumed to occur via this route.

Animals↗

[Stability of acetate buffered methanal solutions].

The determination of the concentration in acetate puffered methanol solutions (formaldehyde solutions) with pH = 5.60 during 14 months disproved the opinion of the limited durability of these solutions. Neither a significant decrease of the methanal mass concentration nor a noticeable change of the pH value could be proved during the period of the examination under different influences of light and temperature. Methanal solutions can be applied farther in the practice of the preservation.

Acetates↗

Cells involved in the immune response. XXX. An evaluation of the different assays to demonstrate rabbit spleen plaque-forming cells. Enhancement of the assay by anti-target cell antibodies.

Four different procedures for the detection of rabbit spleen plaque-forming cells (PFC) directed toward the sheep erythrocyte (SRBC) antigen were evaluated in terms of their sensitivity. These included the conventional localized hemolysis in gel (LHG) assay, the thin-layer LHG assay, the LH assay using a monolayer of the target SRBC erythrocytes and the localized hemolysis in liquid phase (Cunningham) assay. The latter assay consistently proved to be the most sensitive assay. The sensitivity of this latter assay was further improved by incorporating preformed IgG or IgM antibodies directed toward the target erythrocytes, in subhemolytic concentrations, into the assay. This antibody-enhanced plaque assay in liquid medium is 20-50 times more sensitive than the conventional LHG assay.

Animals↗

Memory for prose in Korsakoff and schizophrenic populations.

Twelve alcoholic Korsakoff patients, their 12 alcoholic controls, and 27 institutionalized schizophrenics and their 19 controls, recalled two stories. The clinical populations recalled approximately half as much as their controls, yet recalled the same parts of the stories as their controls. For both groups the ability to process simple prose does not seem to be severely impaired when what is recalled rather than how much is recalled is measured.

Adolescent↗

The antibody-independent cytotoxic activity of normal circulating human leucocytes. II. Failure to demonstrate effector cell-target cell interaction and target cell specificity of the circulating cytotoxic-enhancing factor.

The naturally-occurring antibody-independent cellular cytotoxic activity (NOCC) of normal circulating human monocytes and neutrophils was investigated employing a number of erythrocytes and the K-562 cell line as target cells simultaneously. The identity of the effector cell(s) was shown to be dependent upon or be a function of the type of target cell selected for the assay system. A number of erythrocyte targets (rabbit, horse, sheep and ox erythrocytes) were lysed to varying degrees by neutrophils and monocytes and not by lymphocytes. Irrespective of the red blood cell (RBC) target, the effector monocyte invariably possessed receptors for both C'3 and the Fc of IgG. In contrast, the cytotoxic cells using the K-562 target cell were lymphocytes. Monocytes and neutrophils were inactive. The cytotoxic-enhancing activity in normal human serum exhibits specific and non-specific properties which suggests that more than one factor is involved. With respect to the monocyte cytotoxic cells, only the rabbit erythrocytes could totally absorb the serum factor in a specific fashion. Absorption of the serum with horse, sheep or ox erythrocytes resulted in a significant loss of potentiating activity with respect to all of the erythrocyte targets but a more marked loss of activity using the absorbing erythrocytes as targets. With respect to the polymorphonuclear leucocyte effector cells, only the rabbit RBC were capable of specifically absorbing out the cytotoxic-enhancing factor present in the normal human serum. Absorption of the serum with sheep, horse or ox RBC resulted in total cross-absorption of the enhancing factor. Chicken and human RBC, which do not serve as targets for the NOCC assay, could not absorb out the cytotoxic-enhancing factor with respect to any of the target erythrocytes. The composition of the soluble serum factor(s) is under current investigation but it is not an immunoglobulin since pure serum albumin can substitute for normal serum in the NOCC assay. The mechanism of erythrocyte lysis by the cytotoxic monocyte was investigated. Mononuclear cells were incubated with target cell monolayers and with target cells under optimal rosetting conditions. No interaction between the effector and target cells could be detected. The monocytes did not adhere to the target cell monolayer nor did they form rosettes with the target cells. Thus, the results fail to corroborate or support the assumption that the cytotoxic activity of the monocyte is dependent upon conventionally-detectable receptors. Erythrophagocytosis was not observed to any significant degree under the assay conditions used. Therefore, the nature of the interaction between the cytotoxic monocyte and the erythroid target cell which results in lysis of the target cell remains to be elucidated.

Cell Line↗

The antibody-independent cytotoxic activity of normal circulating human leucocytes. I. Lysis of target cells by monocytes and neutrophils in a non-phagocytic pathway.

Normally circulating human leucocytes were found to consistently lyse rabbit erythrocyte (RRBC) target cells within 24 hr in culture. The reaction is referred to as the naturally-occurring cell-mediated cytotoxic, or NOCC, reaction. Characteristics of this cytotoxic reaction are as follows. (i) The cytotoxic reaction described here can be distinguished from the antibody-dependent cellular cytotoxic (ADCC) reaction as conventional Fc receptors do not appear to play a role. Although the cytotoxic reaction occurs optimally in medium fortified with normal human serum to a final concentration of 1%, neither antibodies nor immunoglobulins in general appear to play a role. Agamma human serum or purified human serum albumin without detectable immunoglobulins are as capable of facilitating and sustaining the NOCC cytotoxic reaction as is normal human serum. Furthermore, foetal calf serum, which promotes the ADCC cytotoxic reaction, inhibits the NOCC cytotoxic reaction. (ii) The NOCC reaction is not a phagocytic one as phagocytosis of the RRBC could not be detected during the culture period. (iii) Monocytes and neutrophils, but not lymphocytes, are capable of lysing the target cells in the NOCC reaction. The effector mononuclear cell is a monocyte with receptors for Fc and C'3. (iv) The NOCC cytotoxic reaction is dependent upon direct effector cell--target cell contact and not upon soluble mediators secreted by the effector cells since third-party bystander erythrocytes are not lysed in the presence of rabbit erythrocyte target cells and human mononuclear cells. Supernatants from lysed RRBC target cells could not lyse fresh RRBC. It is concluded that the NOCC cytotoxic reaction utilizing rabbit erythrocytes as target cells permits the identification of cytotoxic subclasses of monocytes and neutrophils.

Antibody-Dependent Cell Cytotoxicity↗

[Abetalipoproteinemia (author's transl)].

A 21/2-years-old Greek girl with marked failure to thrive and steatorrhea diagnoses to suffer from abetalipoproteinemia by the dissecting microscope appearance of a white intestinal mucosa. This specific finding is due to storage of lipids in the enterocytes. Another typical finding is the acanthocytosis in blood smears. Serum lipids were studied in detail in the patient and her relatives; there was a marked reduction of the low and very low density lipoproteins in the patient only (LDL/VLDL). The most characteristic finding is the lack of apolipoprotein B.

Abetalipoproteinemia↗

The adjuvant treatment of inoperable stage III and IV epidermoid carcinoma of the head and neck with platinum and bleomycin infusions prior to definitive radiotherapy: an RTOG pilot study.

Twenty-nine previously untreated patients with advanced unresectable Stage III or IV epidermoid carcinoma of the oral cavity, oropharynx, hypopharynx, or nasopharynx were entered on a pilot protocol to evaluate the effectiveness and toxicity of platinum-bleomycin infusion chemotherapy administered prior to definitive radiotherapy. Platinum was given by 24-hour continuous I. V. infusion (in an attempt to decrease gastrointestinal and renal toxicity) without mannitol diuresis at a dose of 80--100 mg/m2 on day 1 and repeated on day 22. Bleomycin was administered 15 U/m2 I. V. push on day 3 and was then followed by a five-day continuous I. V. infusion of 15 U/m2/day. Fourteen of 29 (48%) patients achieved an objective partial response on chemotherapy alone (an additional 5 patients or 17% had a minor response). Chemotherapy was well tolerated with 10/29 experiencing no nausea, 4/29 mild nausea alone, and 14/29 experiencing controllable nausea/vomiting. Transient reversible azotemia was noted in 4, skin rash in 3, and anemia in 9 patients. All 29 patients began radiotherapy on day 28; 25 completed radiotherapy and 12/25 (48%) achieved complete tumor clearance; all 12 are currently free of disease with short follow-up. The radiotherapy was well tolerated, completed on schedule, and no unexpected toxicities were encountered. This combined modality approach demonstrated substantial antitumor activity and was able to reduce the significant morbidity from platinum-bleomycin chemotherapy for the treatment of unresectable head and neck carcinoma.

Anemia↗

Pharmacokinetic studies with 3H-cytisine.

The pharmacokinetic behaviour of cytisine was studied in mice by means of tritiated cytisine after intravenous and oral administration of a sublethal dose of 2 mg/kg. After oral administration the maximum blood level is reached after 2 h. The absorption rate is approximately 42%. From the blood level after intravenous administration a half-life of 200 min was calculated. Within 24 h after intravenous administration 32% and after oral administration 18% of the administered radioactivity was excreted into urine. Following intravenous administration 3% of the dose was found in the faeces within 6 h. Among the examined organs and tissues the highest concentrations were reached in the liver, adrenals and kidneys. In the bile the highest concentration after intravenous administration was 200 times that in the blood.

Alkaloids↗

The influence of drugs on the acute toxicity of cytisine.

The effect of various drugs on the acute toxicity of cytisine, the toxic constituent of Laburnum anagyroides Med, was studied in mice. Drugs were tested which have been recommended for symptomatic treatment of laburnum poisoning. Drugs which influence the CNS reduce the acute toxicity of cytisine more effectively than those with predominantly peripheral site of action.

Alkaloids↗