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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 667 records · Page 37Linked to original sources

Case report 161.

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Bone Neoplasms↗

Coronavirus-associated antibodies in nasopharyngeal carcinoma and infectious mononucleosis.

Coronavirus-like particles are found within the cytoplasm of NPC tumor cells, within the cytoplasm of the tumor cells of the regional metastases, and within tumor cells grown on nude mice. For the immunologic identification of the coronaviruses, the cultures of human tracheal epithelium (MRC-C) were used and inoculated with a known coronavirus strain. Whereas blood sera from NPC patients (n = 73) contain significantly elevated antibody titers against corona viruses, unselected sera from patients without NPC showed a low antibody titer (n = 83). Only patients suffering from infectious mononucleosis (n = 40) showed a titer pattern similar to that of NPC patients. For demonstration of antigen-antibody reaction within the NPC tumor cell cytoplasm, sera with a high antibody content against coronaviruses deriving from other than NPC patients or anticoronavirus sera from rabbits were used. By indirect immunofluorescence, the NPC tumor cells showed a bright cytoplasmic fluorescence. No fluorescence was seen when tumor cells were exposed to human sera with known low or absent corona antibody titer or to normal rabbit sera. The results indicate that next to a DNA virus infection (EBV), an RNA virus infection (coronavirus) may play a role in NPC as well as in infectious mononucleosis.

Antibodies, Viral↗

Depression in spinal cord injured patients.

Many regard depression as an inevitable psychological sequela of spinal cord injury. This assumption, if inaccurate, may confound the rehabilitation process. We evaluated 22 patients with recent spinal cord injuries (less than 6 months), using a standardised interview and diagnostic process. Five patients (22 per cent) had diagnosable depressions after their injury. This is higher than the incidence of depression in the general population, but less than anticipated.

Adolescent↗

Expression of biological effector functions by immunoglobulin G molecules lacking the hinge region.

Several biological effector functions mediated by sites on the Fc region of human IgG1 have been studied in two variant IgG1 kappa monoclonal proteins (Dob and Lec) which contain deletions corresponding to the entire hinge region of the heavy chains. Neither Dob nor Lec protein in aggregated form was able to activate the classical complement pathway, and this was shown to be due to an inability to bind the first component of complement (C1). By rosette inhibition assays, Dob and Lec proteins were shown to have no measurable affinity for Fc receptors on human B cells or neutrophils. Dob and Lec proteins had a much reduced affinity for Fc receptors on the murine macrophage-like cell line P388D1 when compared to normal human IgG1. Furthermore, the hinge-deleted proteins were able to compete with murine IgG2b for P388D1 receptors but not with murine IgG2a. In contrast, the binding of Dob and Lec proteins to protein A from Staphylococcus aureus was entirely normal. The functional consequences of the hinge deletion were parallel to those seen when normal IgG1 was reduced and alkylated. It was concluded that the functional impotency of Dob and Lec proteins was related to the close association between the Fab and Fc regions in these molecules and the limited degree of segmental flexibility permitted in the absence of the hinge region. The data also suggest a major role for the C gamma 2 domain (C is the constant region) in mediating effector functions in normal IgG1.

Animals↗

[The latex-IgM-test in virus diagnostic: determination of cytomegalovirus antibodies (author's transl)].

We examined the practical value of the Latex-IgM-test in diagnostic virology. Sera of patients suspected to have a cytomegalic infection were used for serological investigation. Cytomegalovirus produced in cell cultures was incubated with serum from patients. The resulting virus-antibody complex was removed by centrifugation and sensibilized Latex particles were added (anti IgG and anti IgM). The quantity and type of the bound antibody could be determined in this way. The sera were checked by parallel determination by another reliable method, the neutralization test. Immunoglobulins G and M separated and tested for antibodies. The usefulness of the Latex-IgM test for the routine diagnostics could be evaluated in the present study.

Antibodies, Viral↗

[Mechanism of action of an anticonvulsant, sodium dipropylacetate].

The hypothesis that the brain GABA level increase which is induced by a sodium dipropyl acetate treatment arises either through inhibition of succinic semialdehyde dehydrogenase (SSADH), or through inhibition of GABA transaminase by succinic semialdehyde (SSA), has been considered. It appeared that in vivo brain GABA level increase cannot be attributed to SSADH inhibition, and that SSA is not a GABA precursor. It has been shown that SSA is neither in vivo nor in vitro a GABA-transaminase inhibitor. 4-hydroxybenzaldehyde, a potent SSADH inhibitor did not increase GABA level at a dosage which induces a 99% inhibition of SSADH.

4-Aminobutyrate Transaminase↗

Aspects of immunoglobulin G structure relevant to its interaction with Fc receptors.

One unambiguous message that comes from the data obtained relates to the central role played by the hinge region, and its constituent disulfide bonds, in the functioning of the IgG molecule. Segmental flexibility allows variation in the distance between the antibody combining sites, located at the distal ends of the Fab regions, and serves the important function of allowing bivalent attachment of antibodies to antigenic determinants even if the latter form a fixed array, for example, on a cell surface (monogomous bivalency). Too much flexibility, however, seen as a consequence of cleaving the hinge-region disulfides appears to be inimicable to the expression of effector functions. The hinge region and its disulfides control the degree of flexibility, thus allowing the IgG molecule to perform its varied functions.

Animals↗

Clinical features of Strongyloides stercoralis infection in an endemic area of the United States.

Infection with Strongyloides stercoralis, the most common intestinal parasite at our hospital, was encountered in 56 patients over a 3-yr period. The majority of the patients were male adults over 50 years old who had a chronic debilitating associated illness; about half the patients were immunocompromised. Strongyloidiasis was usually a chronic relapsing illness of mild to moderate severity characterized by gastrointestinal complaints (diarrhea, pain, tenderness, nausea, vomiting) and peripheral eosinophilia. Hypoalbuminemia also occurred. Stool examination for larvae was an effective method of diagnosing the parasite, and treatment with thiabendazole was usually successful. The frequent occurrence of S. stercoralis in geriatric patients with other medical problems and the delays in making the diagnosis suggest that the clinical spectrum of strongyloidiasis is greater than generally appreciated by the medical profession. Increased awareness of S. stercoralis is important to prevent the hyperinfection syndrome, which was estimated to occur in 1.5-2.5% of our patients.

Adolescent↗

Kernberg's object-relations theory: a critical evaluation.

Kernberg's rapprochement between Freudian instinct theory and object-relations theory obscures the differences between these two competing theories without taking any recognition of their differences. Rather, Kernberg uses the language of Freudian metapsychology while at the same time purging it of its well-defined meaning, and he fills the resulting theoretical vaccum with ideas taken from the British school of object relations. In so doing Kernberg avoids any serious discussion of the differing concept of the innate postulated by object-relation theorists as opposed to Freudian theory, and the concomitant difference in the importance these two theories ascribe to the mother-infant dyad. His dismissal of the work of Bowlby, Fairbairn, Guntrip and Winnicott is not based on any scientific discussion of their theories but on the fact that these theories reject Freudian motivational theory. Similarly Kernberg ignores the fact that Freud too had an object-relations theory, but implies instead that Freud never fully worked out this aspect of his theory. Kernberg remains unclear as to what he considers to be the importance of the mother-infant dyad. He presupposes the existence of "internalized object relations", and so he never bothers to explain the origins and motives of how this internalization occurs. Thus his "theory" avoids theorizing about what is the crux of the matter--what is it about the external world that is so important to the infant's nature that it becomes transformed into the psyche and perpetuated for a lifetime so that it influences subsequent object interactions and feelings about oneself.

Freudian Theory↗

[Brain tumors with acute or apoplectiform initial symptoms].

A report is given on 31 patients with cerebral tumours, 13 of whom (6.6 per cent) showing apoplectiform and 21 (10.7 per cent of the total number of patients) acute initial symptoms. Apoplectiform courses were equally frequent in malignant and benign tumours, acute courses were predominant in malignant tumours. Development of oedemas and/or local blood flow disturbances were most frequently of pathogenetic importance, followed by haemorrhages and finally circulatory disturbances of the spinal fluid. Prognostically important are dignity and seat of the tumour, not the fact of the dramatic manifestation. Differential-diagnostic problems result most frequently from cerebrovascular haemorrhages. In conclusion casuistics.

Acute Disease↗

Cis-Dichlorodiammine platinum and adriamycin therapy for advanced gynecological and genitourinary neoplasms.

Cis-Dichlorodiammine platinum (DDP) 75 mg/m2 on days 1 and 8 and Adriamycin (ADR) 60 mg/m2 on day 1 were used in 31 patients with advanced gynecological and genitourinary neoplasms. The DDP was given by 6 hours intravenous infusion with 2 liters of 5% Dextrose and 0.5 normal saline using Mannitol and/or furosemide diuresis. Courses were repeated every 21 to 28 days. Responses were seen in 7 of 8 patients with germinal cell neoplasms (5 complete, 2 partial) with a median duration of eight months. A partial response was obtained in 3 of 7 patients with bladder carcinoma with a median duration of three months. There were four partial responses obtained in 9 patients with ovarian carcinoma with a median duration of five months. Toxicities included nausea and vomiting in all 31 patients, nephrotoxicity (serum creatinine > 2 g/100 ml) in patients, tinnitus and/or high frequency hearing loss in 10 patients, and neurotoxicity (peripheral neuropathy, normal pressure hydrocephalus, papilledema) in 8 patients. Severe leukopenia (WBC < 2000/cu mm) and thrombocytopenia (< 100,000/cu mm) occurred in 25% and 45% of evaluable courses, respectively and necessitated dosage reduction in all and delay of therapy in some patients. Peak plasma Pt levels were 2.61 +/- .18 microgram/cc on day 1 and 3.52 +/- .39 microgram/cc on day 8 with a longer terminal half-life on day 8 (252 hours) compared to day 1 (156 hours). Peak plasma ADR levels ranged from .53 to 1.67 N moles/cc with an average terminal half-life of 22.8 hours. This agrees with values of ADR when given alone. This dose and schedule of DDP-ADR is active against advanced gynecological and genitourinary neoplasms, but the amount of toxicity seen indicates that modifications will have to be made.

Adolescent↗

Chédiak-Higashi gene in humans I. Impairment of natural-killer function.

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.

Adult↗

Chédiak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody-dependent cell-mediated cytotoxicity function.

Antibody-dependent cell-mediated cytolysis (ADCC) of human tumor cells by FcR(+) nonadherent effector lymphocytes as well as natural killer (NK) activity was markedly impaired in Chediak-Steinbrinck-Higashi Syndrome (C-HS) patients. Compared to a more than 400-fold defect in NK activity in terms of lytic units, the abnormal ADCC response in C-HS donors was 24-fold below normal suggesting a partial but not complete overlap of lymphocytes or lytic mechanisms responsible for ADCC and NK. The ADCC mechanism against erythrocyte targets, however, was normal, thereby suggesting a qualitative difference in these two forms of ADCC. Other effector-cell functions against tumor-cell targets were normal as measured by (a) spontaneous cytolysis mediated by monocytes, (b) spontaneous cytostasis mediated by neutrophils, and (c) lectin-dependent cytolysis mediated by neutrophils. Although one C-HS patient was low in lectin-dependent cytolysis mediated by lymphocytes, the other C-HS patient was normal, thereby suggesting that cytolytic T function was not linked to the NK-ADCC defect. In addition, the proliferative response to T-dependent mitogens was also relatively normal. These results, combined with other studies showing normal cell-mediated and humoral immunity in these same patients, suggest that patients with C-HS have an immunodeficiency which is selective for NK and ADCC activity.

Adult↗

A new immunodeficiency disorder in humans involving NK cells.

Immunodeficiency disorders have provided much information on the development and interaction of the various B and T lymphoid components in the immune system of man. As the lymphoid system becomes increasingly divided into functional subsets of cells it will be important to find immunodeficiencies affecting newly discovered cell types. Natural killer (NK) cells are a recently described but ill-defined subpopulation of lymphocytes which is thought to play an important part in surveillance against tumour development. Mice homozygous for the beige gene were found to have a selective deficiency in NK function and were more susceptible to transplantation of syngeneic tumours as predicted. We report here that patients carrying the analogous, autosomal recessive Chediak-Higashi (CH) gene have a profound defect in their ability to spontaneously lyse various tumour cells in vitro by either antibody-dependent or independent mechanisms. Since other cell-mediated cytolytic functions were relatively normal, these results suggest that the beige or Chediak-Higashi gene in both man and mouse controls NK function.

Adult↗