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Biomedical subjects

H Stein

Publications and source records attributed to H Stein.

At least 505 records · Page 28Linked to original sources
PubMed1987

Biochemical characterization and biosynthesis of the Ki-1 antigen in Hodgkin-derived and virus-transformed human B and T lymphoid cell lines.

The Hodgkin-associated Ki-1 antigen was analyzed in different cell lines. In Hodgkin analogous L428 cells, biosynthetically labeled with radioactive amino acids, the Ki-1 antibody precipitated three glycoproteins with 90, 105, and 120 kDa, respectively. Surface-labeling revealed that the two larger components were membrane-associated forms of the Ki-1 antigen, although the 90-kDa molecule was shown in pulse-chase experiments to be the precursor of the 105- and 120-kDa forms. All three forms of the Ki-1 antigen possess a tunicamycin-sensitive 6-kDa N-linked carbohydrate moiety. O-Linked oligosaccharides could not be detected. Thus, the differences in m.w. are probably not due to glycosylation. The ionophore monensin prevented the appearance of the membrane-associated molecules, which demonstrated that they are assembled between the transcompartment of the Golgi complex and their insertion into the cell membrane. The 90-kDa precursor molecule cannot be generated by disulfide reduction from the two larger forms. After internal labeling with P-32, only the 105- and 120-kDa bands became visible, indicating that the Ki-1 molecule is phosphorylated after its processing into the two larger membrane-associated forms. Analysis of the Ki-1 antigens from other cell lines demonstrated that after external labeling of two other Hodgkin-derived cell lines, six Epstein-Barr virus lymphoblastoid cell lines and one human T leukemia virus I-positive T cell line, both the 105- and the 120-kDa membrane molecules could be detected, regardless of the presence or type of virus integrated.

Antigens, Neoplasm↗
PubMed1987

Highly potent and specific inhibitors of human renin.

We have designed and synthesized a series of small peptides containing a perfluoroalkyl ketone group at the C-terminal position of the angiotensin I sequence as inhibitors of human renin. From this series of compounds, 8 and 10 showed strong inhibition of human renin (IC50 = 3 X 10(-9), 7 X 10(-9) M, respectively). Compound 10 did not inhibit pepsin and cathepsin D at 10(-4) M. Comparison of the IC50 of compound 8 and compound 11 (8.7 X 10(-7) M) demonstrated the marked effect of the perfluoropropyl group on the potency of inhibition on renin, presumably due to the strong electron-withdrawing effect causing the ketone in 8 to exist predominantly as the hydrate--thus mimicking the tetrahedral transition state during hydrolysis of the scissile Leu10--Val11 amide bond.

Cathepsin D↗
PubMed1987

Phenotype versus immunoglobulin and T-cell receptor genotype of Hodgkin-derived cell lines: activation of immature lymphoid cells in Hodgkin's disease.

Three Hodgkin-derived cell lines (L428, L540, and CO) were studied for rearrangements and expression of immunoglobulin and T-cell receptor genes, and their genotype was compared to the phenotype. As far as the genotype is concerned, all 3 cell lines have characteristics of lymphoid cells; L428 of B, and L540 and CO of T-cell origin. L428 cells have one Ig heavy chain allele rearranged to C gamma and transcribed into RNA, while the second is deleted. Furthermore, L428 cells show an unusual immunoglobulin kappa light chain gene rearrangement involving deletion of the kappa constant gene in one allele, while the remaining kappa and lambda loci are in germline configuration. L540 and CO have, in contrast to L428 cells, the immunoglobulin genes in germline and T-cell receptor genes rearranged. The T-cell receptor beta and gamma genes are rearranged in both L540 and CO, whereas a rearrangement in the alpha locus was detected in L540 cells only. RNA of the size of functional beta chain transcripts was found in CO cells and of the size of functional alpha chain transcripts in L540 cells. All 3 cell lines are classified as immature lymphoid cells with respect to the limited expression of B- and T-cell antigens, respectively, and to the incomplete expression of their antigen receptor. The immaturity of lymphoid differentiation contrasts with the expression of activation antigens, i.e. Ki-1, Ki-24, HLA-DR, and IL-2 receptor. The immaturity of the cells excludes the possibility that the cells were activated along the physiological pathway, i.e. by interaction of the cell with antigen. The results obtained on the cell lines are in accordance with in vivo studies and suggest that Hodgkin and Sternberg-Reed cells are immature lymphoid cells which are activated by a still unknown mechanism.

Cell Line↗
PubMed1987

[2 cases of death following cell therapy].

Fresh-cell therapy is a paramedical procedure whose claimed therapeutic success has not been proven by customary clinical tests (randomized, double-blind trials). In addition, the qualitatively and quantitatively non-standardized parenteral application of heterologous antigens presents considerable danger for the recipient in the form of fatal immune reactions. Two cases are reported in which history, clinical findings and autopsy provided evidence of a causal relationship between cell therapy and death. In one instance, a 75-year-old woman died 30 days after an intramuscular injection of quick-frozen fresh cells from the effects of an immune-complex vasculitis; in the other, a 60-year-old woman died 14 days after "original fresh-cell treatment after Prof. Niehans" from perivenous leucoencephalitis.

Adult↗
PubMed1987

Modified peptides which display potent and specific inhibition of human renin.

A new class of angiotensinogen analogues which contain heteroatom-methylene and retro-inverso amide bond replacements was synthesized and evaluated for renin inhibition. Selected compounds in the series were specific for renin over other aspartic proteinases, and the most potent inhibitor demonstrated hypotensive activity in a salt depleted monkey.

Angiotensins↗
PubMed1987

[Syncopes of unclear etiology. Diagnosis, follow-up observation and pacemaker therapy].

Clinical findings after syncopal attacks were evaluated in 295 inpatients for examining their clinical significance and the course and prognosis in syncopes of unclear aetiology. This was done after having defined the criteria for "very probable" and "possible" causes of the syncopes. A "typically rhythmogenic" anamnesis had a sensitivity rating of 79%. Long-term ECG proved the most frequent contribution to clarification. Doppler examination of the carotid artery was hardly relevant. Patients with tachycardia usually suffered from cardiac disease (coronary heart disease or cardiomyopathy). Bradycardia predominated in patients with a clinically "healthy" heart, especially in elderly patients. An overall percentage of 37% of the cases could not be clarified despite thorough clinical examination using all available diagnostic tools. Follow-ups over two years and outpatient examinations revealed a favourable prognosis in patients whose syncopes had remained unexplained: No further syncopes had occurred in 75% of these patients over a period of two years. In 12% of the subjects the cause was identified by the follow-up examinations. In 95.5% of the patients subjected to pacemaker treatment no syncopes recurred. A relatively small proportion (19.5%) of the patients with unclarified syncopes continued to suffer from syncopes, the aetiology of which could not be determined during the 2-year follow-up period. This group of patients would require better diagnostic techniques, e.g. long-term ECGs over several days or long-term EEGs.

Adolescent↗
PubMed1987

Expression of a Hodgkin and Reed-Sternberg cell associated antigen (Ki-1) in cutaneous lymphoid infiltrates.

Skin biopsy specimens from normal skin and from 115 patients with benign dermatoses, pre- or pseudo-malignant disorders or malignant cutaneous lymphomas have been examined immunohistologically for expression of the Reed-Sternberg cell associated antigen CD30 detected by monoclonal antibodies Ki-1 and Ber-H2. The antibodies stained the atypical cells in lymphomatoid papulosis, a proportion of the neoplastic cells in some cases of mycosis fungoides and most of the neoplastic cells in six large cell anaplastic/pleomorphic non-Hodgkin's lymphomas. The lymphoid cells in all other specimens were Ki-1- and Ber-H2-negative. In all cases, expression of the Ki-1/Ber-H2 antigen was accompanied by expression of activation and proliferation associated markers (i.e., HLA-DR, IL-2 receptor, transferrin receptor and the Ki-67 nuclear antigen). These data indicate the value of antibodies Ki-1 and Ber-H2 in distinguishing between lymphomatoid papulosis and other types of pre- or pseudo-malignant disorders and support the view that lymphomatoid papulosis, Hodgkin's disease and some types of non-Hodgkin's lymphoma constitute a spectrum of related disorders, originated from activated lymphoid cells.

Antibodies, Monoclonal↗
PubMed1987

Growth fraction in human brain tumors defined by the monoclonal antibody Ki-67.

The monoclonal antibody Ki-67, which reacts with cells in the active part of the cell cycle, was used to evaluate immunocytochemically the growth fraction in 22 primary brain neoplasms. The percentage of labelled cells reflected the histological grade of malignancy of each neoplasms. High percentage of Ki-67-positive cells were observed in one choroid plexus carcinoma (60%), one primary melanoma of meninges (40%), three medulloblastomas (40%-50%), one anaplastic astrocytoma and six glioblastomas (10%-40%). One ependymoma had 7% positive cells. Rare positive cells (1%) were present in one pilocytic astrocytoma and one ganglioglioma. Except one negative case, the meningiomas (five cases) had values of positivity ranging from 1% to 6%. Two acoustic schwannomas were negative. These results suggest that immunocytochemical staining with the Ki-67 may be a useful method for measuring the growth fraction in brain neoplasms.

Antibodies, Monoclonal↗
PubMed1987

T-cell lymphomas of the stomach: morphological and immunological studies characterizing two cases of T-cell lymphoma.

Using cytochemical, electron microscopic and immunohistochemical techniques in 20 primary malignant lymphomas of the stomach, we found 18 B-cell and 2 T-cell lymphomas. Primary T-cell lymphoma in the stomach has not been previously reported. The T cells in both cases were reminiscent of T immunoblasts with prominent nucleoli and a basophilic cytoplasm. Case 1 showed a cytological relationship to pleomorphic T-cell lymphoma, large cell type. Case 2 contained in addition some cells not previously described in T-cell lymphomas, resembling immature plasma cells with abundant rough endoplasmic reticulum. Focal positivity to acid phosphatase and dipeptidylaminopeptidase IV suggests the T-cell nature of both lymphomas. In both cases the tumour cells were OKT 11 and OKT 4 positive, and negative for OKT 8. Thus, both cases represent high-grade malignant T-cell lymphomas which correspond phenotypically to T-helper cell lymphoma. Case 2 revealed a further immunohistochemical peculiarity: atypical immunoblasts reacted positively with Ki-1 antibody. Thus, it is a Ki-1 lymphoma of T-cell type.

Adolescent↗
PubMed1987

Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody.

The Ki-67 antibody, a monoclonal antibody that reacts with nuclei in actively proliferating cells, was used in an immunohistochemical study to assess the growth fractions of non-Hodgkin's lymphomas and related disorders. The lowest proliferative indices were found in small lymphocytic lymphoma/chronic lymphocytic leukemia and intermediate lymphocytic/mantle zone lymphoma. An intermediate proliferative index was seen in the follicular lymphomas and diffuse small cleaved cell and diffuse mixed cell lymphomas. A high index was seen in the diffuse large cell lymphoma and lymphoblastic lymphoma. The highest and most consistent proliferative index was seen in small noncleaved cell lymphoma. Cases of reactive follicular hyperplasia had a significantly higher proliferative index than those of follicular lymphoma. We conclude that the Ki-67 antibody has great utility in providing an estimate of the proliferative rate of non-Hodgkin's lymphomas. Prospective studies may show this information to have prognostic value independent of histologic classification.

Antibodies, Monoclonal↗
PubMed1987

New inhibitors of human renin that contain novel Leu-Val replacements.

Stereoselective syntheses of several nonpeptide fragments that function as Leu10-Val11 scissile bond replacements in human angiotensinogen are presented. The opening of N-protected aminoalkyl epoxide 3 with a variety of sulfur, oxygen, nitrogen, and carbon nucleophiles is a key reaction in the preparation of these novel fragments 4-8. The coupling of these fragments to protected dipeptides that mimic positions 8 and 9 in angiotensinogen produces inhibitors of human renin even though the molecules contain no functionality beyond what is formally the Val11 side chain of angiotensinogen. R groups that closely resemble that of the Val side chain are preferable; thus, isopropyl greater than or equal to higher alkyl greater than phenyl greater than substituted phenyl. Sulfur is the best X group; oxidation leads to slight (X = SO2) and significant (X = SO) decreases in inhibitory potency. One such inhibitor, 60, has an IC50 of 13 nM when tested with purified human renin at pH 6.0. The significant activity of these small inhibitors is thought to be due in part to the hydroxyl group of the fragment functioning as a transition-state analogue. Of these, the inhibitors that contain histidine show marked selectivity toward renin over a related aspartic proteinase, pepsin.

Amino Acid Sequence↗
PubMed1987

The management of severe compound war injuries of the extremities in paediatric patients.

Twelve children suffering from severe multiple injuries following mine explosions and extensive crush to the locomotor system are described. An aggressive therapeutic approach in which surgical debridement followed by soft tissue repair was combined with external fixation and hyperbaric oxygen, resulted in the salvage of six limbs. Eleven limbs, crushed beyond repair, were amputated. All children made a surprisingly quick functional recovery.

Amputation, Surgical↗
PubMed1987

Immunohistochemical determination of growth fractions in human permanent cell lines and lymphoid tumours: a critical comparison of the monoclonal antibodies OKT9 and Ki-67.

OKT9 and Ki-67 monoclonal antibodies have recently been proposed as useful tools for evaluating the growth fraction in malignant tumours, with special reference to non-Hodgkin's lymphomas. In particular, while the former is commonly thought to detect a transferrin receptor present on the cytoplasmic membrane of proliferating cells, the latter recognizes a nuclear antigen, which is expressed in G1, S, G2 and M phase of continuously cycling elements. To further verify their reliability, OKT9 and Ki-67 were applied to seven permanent cell lines (four myeloid and three B-lymphoblastoid) and 100 lymphoid tumours (70 non-Hodgkin's and 30 Hodgkin's lymphomas) phenotypically characterized on frozen sections. The results obtained showed that OKT9 and Ki-67 cannot be employed as equivalent means in assessing the growth fraction. In fact, OKT9 is directed to a transferrin receptor which is not only expressed by proliferating cells, but also by some resting elements. On the other hand, Ki-67 provides a nuclear, easily detectable positivity which is restricted to proliferating cells only. Therefore, it seems to represent the only monoclonal which can confidently be employed in the assessment of the growth fraction. Furthermore, the present study underlines that the immunocytochemical analysis of the proliferation rate in tumours gives similar information to the radionucleide uptake assay, while it represents a more sensitive method than the cytofluorimetric evaluation of the DNA content.

Antibodies, Monoclonal↗