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Biomedical subjects

R Newman

Publications and source records attributed to R Newman.

At least 109 records · Page 6Linked to original sources

Laboratory studies in chronic conjunctivitis.

Conjunctival cultures and scrapings for cytological examination were done in 852 cases of chronic conjunctivitis. Bacteria were recovered in 464. Of these, Staphylococcus sp were isolated in 91%; their etiologic importance over normal flora is questionable. Important cytological findings included atypical epithelium (three cases), Halberstaedter-Prowazek inclusion bodies (two), and eosinophils (104). Epithelial degenerative changes were common (585 cases). Crystals (105) and microorganisms (283) were other frequent findings. Active infection seems to be an uncommon cause of chronic conjunctivitis. Cultures are important in avoiding unnecessary antibiotic therapy when no organism is present. Cytological examination can be a helpful diagnostic adjunct in selected cases and is to be recommended especially in chronic follicular conjunctivitis, possible drug toxicity or allergy, dry eye states, and other atypical clinical presentations.

Bacteria↗

Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9.

The monoclonal antibody OKT9 reacts specifically with the receptors for transferrin on human cells (Sutherland, D. R., Delia, D., Schneider, C., Newman, R. A., Kemshead, J., and Greaves, M. F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4515-4519; in Leukemia Markers (Knapp, W., ed) pp. 157-160, Academic Press, New York) and has been used to isolate and characterize this receptor. The receptor is a dimeric glycoprotein (Mr = 180,000) composed of two subunits (Mr = 90,000) and has a pI of approximately 5.2. The transferrin receptor appears to be a transmembrane molecule and is phosphorylated, the phosphate group being predominantly on serine residues. The cell surface form of the molecular possesses both complex and high mannose oligosaccharide chains, which do not appear to have a direct role in antibody (OKT9) binding. The molecule can be cleaved into a Mr = 70,000 fragment from the cell surface, suggesting that the major part of the receptor is exposed to the extracellular environment. The released Mr = 70,000 fragments are not disulfide-linked and possess the antibody (OKT9)- and transferrin-binding sites. Cross-linking studies using radiolabeled transferrin suggest that two molecules of transferrin are bound to each Mr = 180,000 receptor dimer.

Antibodies, Monoclonal↗

Silica fragments from millet bran in mucosa surrounding oesophageal tumours in patients in northern China.

Millet bran is a component of the diet in the area of highest oesophageal cancer incidence in northern China. Millet bran was found to contain up to 20% by weight of silica; some of this silica occurs as friable sheets or sharply-pointed fibres. These types of silica in millet bran are the most likely source of an unusual contamination with fragments of silica found in the oesophageal mucosa surrounding tumours in patients in northern China. A group of mucosal samples analysed together contained over 5,000 particles/g (100 parts per million by weight), ten times as many as were found in tissue from normal controls taken at necropsy in London. The modal diameter was 10 microgram (1-70 microgram). The particles were in the body of the mucosa and were not simply a surface contaminant. Silica fragments and fibres of similar size originating from other plant species occur in the diet in the two other regions of greatest incidence of oesophageal cancer, the Transkei and Iran. If such fragments enter the mucosa, they must cause some degree of trauma, and they may also be able to stimulate proliferation by providing anchorage. These findings suggest the possibility that silica particles might be involved in the aetiology of oesophageal cancer.

Adult↗

Laboratory studies in acute conjunctivitis.

In 84% of 700 consecutive cases of untreated acute conjunctivitis subjected to conjunctival cultures and scrapings, a presumptive etiologic diagnosis could be made based on standard microbiologic and cytologic criteria. Of these 583 cases, 264 were bacterial, 245 were viral, 51 were allergic, and 17 were chlamydial. In 75% of the cases, clinical impressions were consistent with laboratory findings. On the basis of these results, laboratory workup is recommended in (1) follicular conjunctivitis to differentiate viral from chlamydial processes, (2) purulent conjunctivitis to identify pathogens and decide on appropriate antimicrobial therapy based on sensitivity data, and (3) those cases in which the clinical picture is not sufficiently distinctive to suggest an etiologic diagnosis.

Acute Disease↗

Human MHC class II molecules as differentiation markers.

DA6.231 and DA6.164 are mouse monoclonal antibodies that immunoprecipitate HLA-DR-like p34,29 glycoprotein dimers from surface- and metabolically-labeled cells. On lymphoblastoid cell lines the distribution of the 231 epitope is completely nonpolymorphic, while the 164 epitope is present on all cells except on those that are DR7 homozygous. Binding-inhibition studies show that the 231 and 164 epitopes are spatially close to each other when present on the same molecule. The mutual inhibition pattern and the absence of the 164 epitope from the 231+ cells of a few leukemia patients suggest, however, that 231 and 164 epitopes are not invariably present together. Most DR-positive cells possess 231+ and 164+ and 231+ 164- class II molecules in approximately a 2:1 ratio. This has been confirmed by immune depletion studies. Thus DA6.231 appears to define a supralocus epitope. The 164 epitope may be a marker for a subset of class II molecules exhibiting differential expression on various cell types immortalized by malignant transformation.

Antibodies, Monoclonal↗

Controlled trial of imipramine for chronic low back pain.

Chronic low back pain is a common problem that has been noted in several studies to exist as a component of masked depression. To determine the usefulness of imipramine in the treatment of chronic low back pain, either by a direct action or indirectly via resolution of a depressive equivalent, 50 consecutive patients were entered into a controlled trail that employed serum imipramine and desipramine levels and Beck depression questionnaires. Forty-one patients completed the study, and 48 were used in the statistical analysis. Imipramine had a statistically significant effect over placebo in most, but not all, of the clinical parameters that were measured. A linear relationship between serum drug levels and reported symptoms was not noted. Only 10 of the 50 patients entered into the study were judged clinically depressed and, of these, 7 were depressed according to standard criteria. There was no statistically significant difference noted in either the initial or the change in Beck depression scores between those on imipramine and those on placebo. However, among those on the active drug, the patients with a greater symptomatic response had a simultaneous change in the total Beck depression scores (toward less depression) that approached statistical significance when compared with those with a less symptomatic response. Although the results are not conclusive, imipramine may possibly be useful in the treatment of chronic low back pain, especially so when it exists as a component of masked depression.

Adult↗

Results of treatment for squamous carcinoma of the lower gum.

The records of 61 patients with a diagnosis of squamous carcinoma of the lower alveolar ridge were reviewed. The overall two-year survival was 67% with a local or regional failure of 5%. The majority of patients were treated with surgery initially with an excellent local control of 98%, if the patient who died in the postoperative period and the patient lost to follow-up are excluded. Radiation therapy should be used postoperatively for those patients whose cancer exhibits some of the adverse findings such as extensive nodal metastasis, perineural invasion, or inadequate margins of surgical resection.

Adult↗

P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody.

This study was directed at surface structures that are found on human lymphohemopoietic progenitor cells in normal and leukemic bone marrow. A monoclonal antibody was produced against an acute lymphoblastic leukemia (ALL) cell line of the pre-B phenotype; this antibody (BA-2) was used to demonstrate a cell surface polypeptide of approximately 24,000 mol wt that migrates similarly in both reduced and nonreduced form. This polypeptide, p24/BA-2, was shown by immune precipitation and gel electrophoresis and cell distribution studies to be different from HLA-DR and gp 100/cALLa. p24/BA-2 was present on the surface of 77% (54/70) of cases of non-T, non-B ALL; BA-2 staining was less bright or nondetectable in surface Ig+ (SIg+) chronic lymphocytic leukemia (CLL) and T ALL and nondetectable on peripheral T and B lymphocytes. Approximately 3% of bone marrow mononuclear cells were p24/BA-2+, and these cells were E rosette-, surface (SIg-), and nonphagocytic. Marrow TdT+ progenitor cells were frequently p 24/BA-2+. Results suggest that p24/BA-2 represents a surface structure present on lymphohemopoietic bone marrow progenitor cells and that most common types of ALL bear the p25/BA-2 structure.

Antibodies↗

Mapping cell surface antigen expression of haemopoietic progenitor cells using monoclonal antibodies.

A library of monoclonal antibodies which show selective reactivity with particular cells or gene products (e.g. HLA-DR, glycophorin) of different cell lineages in the haemopoietic system has been compiled. Using these probes in conjunction with the fluorescence-activated cell sorter (FACS) the pattern and sequence of cell surface antigenic expression on haemopoietic progenitor cells have been mapped. A cell is identified in bone marrow which has a unique membrane phenotype and the nuclear enzyme terminal deoxynucleotidyl transferase. Its composite phenotype is identical to that seen in the common variant of acute lymphoblastic leukaemia (ALL). It is suggested that this cell is a putative B lineage progenitor which provides the major target for ALL. Detailed analysis of erythroid differentiation with monoclonal antibodies on the FACS reveals an intriguing pattern of antigenic expression in which HLA-DR, glycophorin and band III appear in sequence. HLA-DR (Ia-like antigen) may be present on all or most committed haemopoietic progenitor cells and could play an important role in cell interactions regulating early haemopoiesis.

Animals↗

Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.

A murine monoclonal antibody (OKT9) raised against human leukemic cells binds to a wide variety of leukemia and tumor cell lines and to a minority of leukemia cells taken directly from patients. Fetal thymus and liver are strongly reactive as are some normal, immature hemopoietic cells and activated lymphocytes. Reactivity with OKT9 appears to correlate with proliferation status in both normal and malignant populations. Biochemical analysis indicates that this structure is a approximately equal to 180,000-dalton glycoprotein with two disulfide-bonded subunits of approximately equal to 90,000-daltons. Isolation of the transferrin receptor from a T-cell line (MOLT-4) indicates that it also has a dimeric approximately equal to 180,000-dalton structure. Radio-labeled transferrin bound to its receptors can be specifically precipitated by the monoclonal OKT9, although the latter does not bind transferrin itself, indicating that the antigenic structure defined by this antibody is likely to be the transferrin receptor.

Animals↗

Exploitation of monoclonal antibodies: a "who's who" of haemopoietic malignancy.

A library of monoclonal antibodies plus "conventional' markers (e.g. anti-TdT) have been used to explore the detailed phenotypes of leukaemic cells in relation to normal haemopoietic differentiation. This analysis reveals that consistent, composite phenotypes of different subclasses of lymphoid malignancies closely mimic those of corresponding normal cells at equivalent levels of maturation. It is suggested that three major target cell populations are available for lymphoid malignancy: the pluripotential stem cell (e.g. "lymphoid' blast crisis of CGL), lymphoid progenitors or stem cells in the bone marrow (non-T ALL) or thymus (T-ALL, T-NHL) and long lived, mature and immunocompetent T and B cells (T-CLL, PLL, Sézary and B-CLL, lymphoma respectively). The major phenotypes documented in different leukaemias represent the level of "maturation arrest' imposed on the dominant subclone; this is determined by, but not necessarily synonymous with, the "target cell' and associated clonogenic cell population in the leukaemia. No consistent major abnormalities of gene expression are revealed by this investigation and although they may exist (e.g. loss or acquisition of antigens with malignant progression) we suggest that they are irrelevant to the central issue of what alterations are essential and sufficient for the evolution of clonogenic leukaemic cells. We propose instead that subtle changes, which uncouple proliferation and differentiation, are all that is required.

Antibodies, Monoclonal↗

Conjunctivitis in the newborn: observations on incidence, cause, and prophylaxis.

One hundred seventy-one cases of neonatal conjunctivitis seen at Bellevue Hospital during the period 1950--1976 were reviewed. An overall incidence of 3.0 cases per 1,000 live births was found. A comparison of the rates of neonatal conjunctivitis with silver nitrate and tetracycline prophylaxis revealed a 100% increase in the rate overall, as well as the rate of gonococcal conjunctivitis with tetracycline. Using conjunctival cultures and cytology, a diagnosis could be established in 73% of the cases, with 41% being bacterial and 32% chlamydial. Staphylococcus was the single most common organism recovered; gonococcus was relatively rare.

Bacterial Infections↗

An experimental study of the ventral striatum of the golden hamster. I. Neuronal connections of the nucleus accumbens.

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the nucleus accumbens. Following iontophoretic applications or hydraulic injections of HRP in nucleus accumbens, cells labeled by retrograde transport of HRP were observed in the ipsilateral telencephalon in the posterior agranular insular, perirhinal, entorhinal, and primary olfactory cortices, in the subiculum and hippocampal field CA1, and in the anterior and posterior divisions of the basolateral amygdaloid nucleus. In the diencephalon, labeled neurons were present ipsilaterally in the central medial, paracentral and parafascicular intralaminar nuclei, and in the midline nuclei parataenialis, paraventricularis, and reuniens. Retrograde labeling was observed in the ipsilateral brainstem in cells of the ventral tegmental area and dorsal raphe. Many of these projections to nucleus accumbens were found to be topographically organized. Anterograde transport of HRP from nucleus accumbens demonstrated ipsilateral terminal fields in the ventral pallidum and substantia nigra, pars reticulata. The afferent projections to nucleus accumbens from the posterior insular and perirhinal neocortices, intralaminar thalamus, and the dopamine-containing ventral tegmental area are analogous to the connections of the caudatoputamen, as are the efferents from nucleus accumbens to the substantia nigra and ventral globus pallidus. These connections substantiate the classification of nucleus accumbens as a striatal structure and provide support for the recently proposed concept of the ventral striatum. Furthermore, the demonstration that a number of limbic system structures, including the amygdala, hippocampal formation, entorhinal cortex, and olfactory cortex are important sources of afferents to the nucleus accumbens, suggests that the ventral striatum may serve to integrate limbic information into the striatal system.

Amygdala↗

An experimental study of the ventral striatum of the golden hamster. II. Neuronal connections of the olfactory tubercle.

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the olfactory tubercle. Following iontophoretic applications or hydraulic injections of HRP in the tubercle, neurons labeled by retrograde transport of HRP were observed ipsilaterally in the telencephalon in the main olfactory bulb, the medial, lateral, ventral, and posterior divisions of the anterior olfactory nucleus, and in the orbital, ventral, and posterior agranular insular, primary olfactory, perirhinal, and entorhinal cortices. Labeled cells were also present in the basolateral, basomedial, anterior cortical, and posterolateral cortical amygdaloid nuclei, and bilaterally in the nucleus of the lateral olfactory tract. In the diencephalon, ipsilateral HRP-containing neurons were observed in the midline nuclei paraventricularis, parataenialis, and reuniens, and in the parafascicular intralaminar nucleus. Retrograde labeling was present in the ipsilateral brainstem in cells of the ventral tegmental area, substantia nigra, and dorsal raphe. Many of the above projections to the tubercle were found to be topographically organized. Anterograde axonal transport of HRP from the olfactory tubercle labeled terminal fields ipsilaterally in all parts of the anterior olfactory nucleus, in the ventral pallidum, and in the substantia nigra, pars reticulata. Contralaterally, terminal fields were present in the dorsal and lateral divisions of the anterior olfactory nucleus. The projections to the tubercle from the orbital, ventral, and posterior agranular insular, and perirhinal neocortices, intralaminar thalamus, and dopamine-containing areas of the ventral mesencephalon are analogous to the connections of the caudatoputamen, as are the efferents from the tubercle to the ventral globus pallidus and substantia nigra. These connections substantiate the recent suggestion that the olfactory tubercle is a striatal structure, and provide support for the ventral striatal concept. In the present study of the olfactory tubercle, and in the first study in this series on the nucleus accumbens, the ventral striatum was found to receive projections from a number of limbic system structures, including the main olfactory bulb, anterior olfactory nucleus, amygdala, hippocampus, and subiculum, and the entorhinal and primary olfactory cortices. These findings suggest that the ventral striatum is concerned with integrating limbic information into the striatal system.

Amygdala↗

Primary extramedullary plasmacytoma of the omentum associated with recurrent adenocarcinoma of the colon: first case report.

Extramedullary plasmacytomas are rare tumors, with 272 cases reported in the literature in English. Less than 10 per cent of these are located in the gastrointestinal tract. This report documents the first primary plasmacytoma of the omentum in association with a recurrent colonic adenocarcinoma. Extramedullary plasmacytoma, a B cell neoplasm, characteristically arises in areas containing lymphoid tissue. In our case the tumor most likely arose in a lymph node or nodes in the omental fat, with subsequent replacement of the entire greater omentum and involvement of the colonic serosa by direct extension. Although the extent and nature of the association between myeloma and carcinoma remain obscure, a review of the literature suggests that such association may occur more frequently than has been supposed. Further investigation would appear to be warranted.

Adenocarcinoma↗

Contamination in McCarey-Kaufman stored keratoplasty donor material.

One hundred consecutive donor corneas which had been preserved in McCarey-Kaufman medium and used in actual keratoplasties were studied. The residual medium and button remnants were cultured for bacterial and fungal growth. Coagulase-positive staphylococci were recovered in three cases, coagulase-negative staphylococcus in one and Rhodotorula sp. in another; no associated postoperative infections were reported, although one patient was regrafted 48 hours after the initial keratoplasty for "graft decompensation"--the initial button was not submitted for reculture. One additional specimen was processed. A cracked vial with clear contained fluid was held for culture; Pseudomonas cepacia was grown from the fluid. Other samples in undamaged vials from the same lot did not show contamination.

Anti-Bacterial Agents↗