Influence of Side Chain Interdigitation on Strain and Charge Mobility of Planar Indacenodithiophene Copolymers.

Indacenodithiophene (IDT) copolymers are a class of conjugated polymers that have limited long-range order and high hole mobilities, which makes them promising candidates for use in deformable electronic devices. Key to their high hole mobilities is the coplanar monomer repeat units within the backbone. Poly(indacenodithiophene-benzothiadiazole) (PIDTC16-BT) and poly(indacenodithiophene-thiapyrollodione) (PIDTC16-TPDC1) are two IDT copolymers with planar backbones, but they are brittle at low molecular weight and have unsuitably high elastic moduli. Substitution of the hexadecane (C16) side chains of the IDT monomer with isocane (C20) side chains was performed to generate a new BT-containing IDT copolymer: PIDTC20-BT. Substitution of the methyl (C1) side chain on the TPD monomer for an octyl (C8) and 6-ethylundecane (C13B) afford two new TPD-containing IDT copolymers named PIDTC16-TPDC8 and PIDTC16-TPDC13B, respectively. Both PIDTC16-TPDC8 and PIDTC16-TPDC13B are relatively well deformable, have a low yield strain, and display significantly reduced elastic moduli. These mechanical properties manifest themselves because the lengthened side chains extending from the TPD-monomer inhibit precise intermolecular ordering. In PIDTC16-BT, PIDTC20-BT and PIDTC16-TPDC1 side chain ordering can occur because the side chains are only present on the IDT subunit, but this results in brittle thin films. In contrast, PIDTC16-TPDC8 and PIDTC16-TPDC13B have disordered side chains, which seems to lead to low hole mobilities. These results suggest that disrupting the interdigitation in IDT copolymers through comonomer side chain extension leads to more ductile thin films with lower elastic moduli, but decreased hole mobility because of altered local order in the respective thin films. Our work, thus, highlights the trade-off between molecular packing structure for deformable electronic materials and provides guidance for designing new conjugated polymers for stretchable electronics.

Color, composition, and thermal environment of Kuiper Belt object (486958) Arrokoth.

The outer Solar System object (486958) Arrokoth (provisional designation 2014 MU69) has been largely undisturbed since its formation. We studied its surface composition using data collected by the New Horizons spacecraft. Methanol ice is present along with organic material, which may have formed through irradiation of simple molecules. Water ice was not detected. This composition indicates hydrogenation of carbon monoxide-rich ice and/or energetic processing of methane condensed on water ice grains in the cold, outer edge of the early Solar System. There are only small regional variations in color and spectra across the surface, which suggests that Arrokoth formed from a homogeneous or well-mixed reservoir of solids. Microwave thermal emission from the winter night side is consistent with a mean brightness temperature of 29 ± 5 kelvin.

The biology of tumor growth in the non-Hodgkin's lymphomas. A dual parameter flow cytometry study of 220 cases.

Dual parameter flow cytometry studies (cell DNA content and electronic cell volume) were performed in 220 cases of non-Hodgkin's lymphoma. All cases were characterized as B or T cell malignancies, based on immunologic surface marker characteristics. Aneuploidy by flow cytometry was more common among the B cell lymphomas than among the T cell lymphomas, and was most common among the large B cell lymphomas and B cell lymphomas of intermediate size. Ploidy index distributions showed a prominent hyperdiploid peak, as well as tumor cell populations with near-tetraploid DNA contents. In serial studies, a decrease in ploidy index was observed in association with clinical and histologic transformation in one case. The highest S fractions were observed among the large and intermediate B cell lymphomas and among the aggressive T cell lymphomas. In clinical samples consisting of mixtures of diploid and aneuploid populations, the data on the aneuploid components could often be separated from other components of the mixture in multiparameter studies on the basis of the larger electronic cell volumes of the aneuploid cells. In each case, the aneuploid large cell component almost invariably had a higher S fraction than the residual component(s) of the mixture. Overall, the data are consistent with a model of clonal selection and clonal evolution in the lymphomas in which early cytogenetic abnormalities that involve little or no change in total cell DNA content are followed by cell tetraploidization that is associated with cytogenetic instability and chromosome loss over the course of time.

Surface immunoglobulin on leukemic, leukemoid, and normal granulocytes.

Using a new functional approach for the study of lymphomas and leukemias in which immunologic and cytochemical techniques were employed, we found a consistent surface immunoglobulin pattern of the gamma-, k-, lambda-type on cells from poorly differentiated (acute) and well-differentiated (chronic) granulocytic leukemias. This pattern was also found on nonneoplastic granulocytes from patients with leukemoid reactions as well as on granulocytes from normal individuals. These findings suggested that both leukemia cells and nonneoplastic granulocytes had IgG bound to the cell surface by an Fc receptor. This binding of IgG by granulocytes was not tumor-specific and appeared to correlate both with the degree of differentiation and possibly with the degree of activation of the granulocytes. In addition to raising the basic question of its functional significance, these findings offered an approach for distinction of poorly differentiated granulocytic leukemia from lymphomatous processes.

Morphologic and cytochemical comparison of human lymphoblastoid T-cell and B-cell lines: light and electron microscopy.

Human lymphoblastoid cell lines characterized as T- or B-cells by various markers were compared morphologically and cytochemically by light and electron microscopy. Distinct differences in nuclear morphology, amount of cytoplasm, pyroninophilia, and periodic acid-Schiff (PAS) staining enabled us to discriminate between T- and B-cell lines. T-cells had nuclei with an irregular configuration, stippled heterochromatin, and small or absent nucleoli. The scanty cytoplasm of T-cells contained intensely stained, PAS-positive globules and was less pyroninophilic than the cytoplasm of B-cells. B-cells had more rounded, uniform, vesicular nuclei with prominent nucleoli and peripheral heterochromatin. The cytoplasm of B-cells was abundant and strongly pyroninophilic. Transmission electron microscopy generally confirmed these morphologic differences. These findings supported our contention that consistent cytologic features concordant with immunologic markers make it possible to identify certain lymphomas as being of B- or T-cell origin on purely morphologic grounds.

Two new monoclonal antibodies, Lym-1 and Lym-2, reactive with human B-lymphocytes and derived tumors, with immunodiagnostic and immunotherapeutic potential.

Two new monoclonal antibodies (Lym-1 and Lym-2), reactive with the cell surface of B-lymphocytes and derived tumors, have been produced using tumor cell nuclei preparations as immunogens. Specificity screens using live cell radioimmunoassay techniques with 52 well-characterized human lymphoma and leukemia cell lines showed that both Lym-1 and Lym-2 bound to cell lines of B-cell lineage but were unreactive with those of T-cell, myeloid, or erythroid derivation. The B-cell specificity of these reagents was confirmed on 36 lymphoma and 15 leukemia biopsy specimens by using immunoperoxidase or immunofluorescence techniques. Additionally, flow cytometric analysis of 22 lymphoma biopsies showed that the majority of B-cell tumors were Lym-1 and/or Lym-2 positive and that within a given biopsy, a high percentage of the malignant cell population was stained. In both the immunoperoxidase and flow cytometric studies, reactive T-cells or T-cell lymphomas were consistently negative with the exception of Hodgkin's disease tissues which, in some instances, showed a higher than expected positivity with Lym-1 and Lym-2. Approximately 40% of B-cell chronic lymphocytic leukemias were found to be positive with Lym-1 while 80% were positive with Lym-2. Immunoperoxidase staining of frozen sections of human lymphoid tissues showed that both Lym-1 and Lym-2 stained germinal center and mantle zone B-lymphocytes as well as interfollicular histiocytes. Flow cytometric analysis of normal peripheral blood demonstrated specific staining of B-cells which comprised approximately 8% of circulating lymphocytes. Immunoperoxidase staining of nonlymphoid human organs and tissues revealed weak reactivity of Lym-1 with surface colonic epithelium only. Consistent with these findings, 35 solid tumor cell lines of diverse nature were found unreactive with both Lym-1 and Lym-2. Although standard techniques have thus far failed to identify the antigen recognized by Lym-2, the membrane antigen which binds Lym-1 has been shown by immunoprecipitation and competitive radioimmunoassay studies to be a polymorphic variant of the HLA-Dr antigen. Solid-phase radioimmunoassay techniques have shown that the antigens recognized by Lym-1 and Lym-2 are not significantly modulated after antibody exposure nor shed into the circulation of lymphoma patients. Finally, using iodine-125 labeled preparations of purified Lym-1 and Lym-2, we have determined that both reagents have a relatively large number of antibody binding sites per tumor cell and increased avidity for lymphoma cells when compared to normal and reactive lymph node B-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Results of initial lymph node biopsy in homosexual men with generalized lymphadenopathy.

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.

Human T-cell lymphotropic virus type III associated disorders. The spectrum in the heterosexual population.

Eleven heterosexual patients (nine women, two men) without classic risk factors for development of acquired immunodeficiency syndrome (AIDS) were seen between March 1983, and April 1985, and diagnosed as having AIDS (four), persistent, generalized lymphadenopathy (PGL) (four), or asymptomatic human T-cell lymphotropic virus type III (HTLV-III) carrier state (three). The clinical presentations and course of those with AIDS or PGL were similar to those reported in homosexual men with AIDS or PGL, with reversed T4/T8 ratio, and the presence of antibody to HTLV-III. Asymptomatic carriers had normal T4/T8 ratios, had an absence of HTLV-III antibodies, but had HTLV-III virus cultured from blood. We conclude that the heterosexual population, with or without history of sexual exposure to individuals at risk for AIDS, may develop a wide range of clinical manifestations secondary to HTLV-III, varying from AIDS to the asymptomatic carrier state.

B-cell lymphoma in two monogamous homosexual men.

Opportunistic infections and malignant neoplasms have been described in homosexual men in association with immunologic abnormalities. We observed the development of malignant B-cell lymphomas in two homosexual men who had had a monogamous relationship for two years. Patient 1 had an aggressive, monoclonal, small, noncleaved, non-Burkitt's lymphoma ("undifferentiated lymphoma"), associated with severe immunocompromise. Patient 2 manifested a monoclonal, small, cleaved, follicular center cell lymphoma, with a follicular pattern, two months later. No common acute infection was detected. Staining for Epstein-Barr nuclear antigen in malignant tissue was negative in the second patient. However, the possibility of a transmissible agent as a causative factor cannot be excluded, and further study of similar patients is warranted.

Rectal lymphoma in homosexual men.

Lymphoma of the rectum is a rare tumor and in most studies is not separated from other lymphomas of the large intestine. We have recently examined four homosexual men with lymphoma presenting in the rectum. Symptoms included rectal bleeding in three, pain on defecation in two, and mucoid rectal discharge in two. Systemic "B" symptoms (ie, fever, night sweats, and/or weight loss), as well as a rectal mass, were present in all four. All were high-grade tumors, with B-cell immunoblastic sarcoma in two and small noncleaved Burkitt-like lymphoma in two. Intracytoplasmic immunoperoxidase staining revealed monoclonal kappa light chains in three tumors, whereas the fourth was nonstaining. Immunologic abnormalities were similar to those reported in patients with acquired immunodeficiency syndrome. Antibodies to human T-cell lymphotropic virus type III were found in the three cases tested, and retrovirus was cultured from lymphomatous tissue in one. Despite multiagent chemotherapy, two patients died within six months of diagnosis and a third has recently suffered relapse within the central nervous system.

Lymphocyte immunophenotypes among anti-HTLV-I/II-positive blood donors and recipients. The Transfusion Safety Study Group.

The Transfusion Safety Study retrospectively screened a repository of serum specimens collected in late 1984-early 1985 to identify blood donors with antibody to human T-cell lymphotropic virus (HTLV) at that time. They and their recipients have been traced for additional HTLV studies. Immunophenotypic analyses of peripheral blood lymphocytes from nine anti-HTLV-positive recipients, assumed to be infected during or since late 1984, showed no significant changes from healthy controls. Evaluation of the immunophenotypes of the 48 donors, however, showed significant elevations in the absolute counts of the T-cell (CD2) and natural killer (CD56) populations, the T helper/inducer and suppressor/inducer subsets (CD4+ CD29+ and CD4+ CD45RA+), and changes in T-cell activation markers. Long-term but not recent HTLV infection appears to alter the T-cell immunophenotypic pattern. Both infection with HTLV and human immunodeficiency virus type 1 are associated with a decreased CD2+ CD26+ count.

Lymphocyte immunophenotyping in an elderly population: age, sex and medication effects--a flow cytometry study.

Flow cytometry studies of 179 individuals aged 55-95 years reveal correlations of various hematological and immune cell measures (quantification of leukocytes, leukocyte subtypes, platelets, and erythrocytes) with age, sex, common medications (aspirin, ulcer therapy, estrogen replacement therapy), and health history variables (minor arthritis, allergy, smoking, stress and exercise). Possible reasons for some of these findings are discussed.

Primary central nervous system lymphoma in homosexual men. Clinical, immunologic, and pathologic features.

Primary central nervous system lymphoma constitutes one of the criteria for the acquired immune deficiency syndrome (AIDS), yet a paucity of information is currently available regarding the clinical, immunologic, or pathologic features of these patients. Six homosexual men presenting with primary central nervous system lymphoma were evaluated. Five of these patients presented with altered mental status. All lymphomas were intracranial. B cell immunoblastic sarcoma was found in five. Immune phenotyping studies performed in five patients revealed monoclonal lambda light chain in three, whereas one expressed only IgG heavy chain, and one demonstrated another B cell (LN-1) surface antigen. Hypodense, contrast-enhancing lesions were apparent on computed axial tomographic scanning of the brain, in sharp contrast to isodense or hyperdense lesions reported in primary central nervous system lymphomas without underlying immunodeficiency. Immunologic abnormalities in these patients were similar to those in AIDS presenting as Kaposi's sarcoma or with opportunistic infections. In spite of therapeutic interventions, survival was short, and only one patient is currently alive.

Progressive histopathologic abnormalities in the persistent generalized lymphadenopathy syndrome.

Using a quantitative classification, we evaluated serial lymph node biopsies in 20 homosexual men with Persistent Generalized Lymphadenopathy (PGL), and correlated the results with peripheral blood lymphocyte counts and clinical findings. In a median follow-up interval of 19 months, ten patients (50%) had progression from one histologic subtype of this disorder to another. Lymph nodes from the other 10 patients also demonstrated decreased numbers of organized follicles in the most recent specimens, in addition to progressive abnormalities of other histologic parameters and peripheral blood T4 counts. This suggests that these patients do not have stable disease. However, in a median follow-up interval of 19 months, only one (5%) of the patients had developed AIDS. We conclude that progressive lymph node histopathologic subtypes do not correlate well with decreased T4 lymphocyte counts or clinical course over a short time interval.

Smooth muscle tumors of the gastrointestinal tract. Flow cytometric quantitation of DNA and nuclear antigen content and correlation with histologic grade.

Simultaneous flow cytometric quantitation of DNA content and the proliferation-associated nuclear antigen p105 was performed on 41 gastrointestinal smooth muscle neoplasms and the results were correlated with histologic features. Aneuploid DNA stemlines were found in 17 cases (41%), including four of 15 (21%) tumors of unknown malignant potential, eight of 17 (47%) low-grade leiomyosarcomas, and five of seven (71%) high-grade leiomyosarcomas. In 10 of the 17 aneuploid tumors, an aneuploid peak was clearly identified on the single parameter DNA histogram, with a mean DNA index of 1.36. In the other seven aneuploid cases, a near-diploid, aneuploid population (mean DNA index, 1.08) was identified only by simultaneous immunofluorescence for p105. Clinical follow-up information was available for 14 patients. Mean survival of 10 patients with aneuploid tumors was 32 months, whereas mean survival of four patients with diploid tumors was 51 months. Of the seven patients who died within 1 year of diagnosis, six had aneuploid leiomyosarcomas. These findings demonstrate that DNA aneuploidy is common in high-grade gastrointestinal leiomyosarcomas and may be associated with shortened survival.

Low-density mononuclear cells. Potent stimulators of the human MLR.

We have applied purification strategies similar to those used to purify murine dendritic cells to human peripheral blood in an attempt to enrich for stimulators of the human mixed lymphocyte reaction (MLR). Equilibrium density centrifugation of peripheral blood mononuclear cells yields a population of low density cells that are potent stimulators of a human MLR. The stimulator cells are Dr+, nonlymphocytic, and weakly adherent. Strongly adherent monocytes, also present in the low-density cell population, do not stimulate a human MLR. This contrasts with other human MLR studies that ascribe stimulatory activity to adherent monocytes, and it indicates functional and morphological heterogeneity among monocytes.

Double labeled-antigen method for demonstration of intracellular antigens in paraffin-embedded tissues.

A double "labeled-antigen" method has been developed for the simultaneous staining of both kappa and lambda light chains in fixed paraffin sections. The method is a two step procedure utilizing a mixture of antisera against kappa and lambda light chains in the first stage, followed by the addition of a mixture of kappa antigen labeled with horseradish peroxidase and lambda antigen labeled with alkaline phosphatase. The selection of substrates yielding reaction products of contrasting color enabled the observer to distinguish kappa-containing cells (brown) from lambda-containing cells (blue). Reactive plasma cells stained either pure brown (kappa) or clear blue (lambda) in a ratio of 1.5:1. Blood vessels containing serum immunoglobulins showed a mixed brown-blue reaction, as did the Reed-Sternberg cells of some cases of Hodgkin's disease. The advantages of this double labeled-antigen method over previously reported methods for achieving double staining are discussed.

Immunoblastic sarcoma of T- and B-cell types: morphologic description and comparison.

Immunoblastic sarcoma (IBS) is a large cell lymphoma conceptually related to transformed T and B lymphocytes of the extrafollicular compartment of the immune system (immunoblasts). This light microscopic study of a series of 47 immunologically defined cases of IBS was undertaken in an attempt to define more precisely the morphologic features of the T- and B-cell subtypes. A remarkable morphologic spectrum characterized T-IBS (31 cases), which could be divided into two main groups: 1) tumors composed of varying mixtures of small, medium-sized, and large transformed cells; and 2) tumors with more homogeneous populations of medium-sized or large transformed cells. These cells, in all sizes, generally had abundant pale-staining cytoplasm, delicate nuclear membranes, finely dispersed chromatin, and one to several, small or medium-sized, prominent nucleoli. A distinctive background of small, irregular lymphocytes was frequently present. Plasmacytoid differentiation, seen most consistently as amphophilic staining of the cytoplasm, generally characterized B-IBS (16 cases). B-IBS similarly showed a morphologic spectrum that occurred in two main forms: 1) tumors consisting of a spectrum of transformed cells, with the smaller cells often showing the most striking plasmacytoid differentiation; and 2) tumors consisting predominantly of medium-sized to large transformed cells with varying degrees of plasmacytoid differentiation. With this constellation of features, all but two cases of T-IBS and one case of B-IBS were morphologically distinguishable.

Endobronchial disease and racial differences in pulmonary sarcoidosis.

In a retrospective review of 7 years of Walter Reed Army Medical Center fiberoptic bronchoscopy records, 154 patients with biopsy specimen proved (122) and clinically diagnosed (32) sarcoidosis were identified. Endobronchial mucosal appearance was normal in only 70 (45%). Abnormal mucosal findings included erythema (29 patients), nodules (13), plaques (13), and cobblestoning (29). Fifty-nine patients were evaluated with endobronchial biopsies (EBBX), and non-necrotizing granulomata diagnostic of sarcoidosis were found in 42 (71%). The diagnostic yield from endobronchial biopsies was similar regardless of the type of mucosal abnormality. EBBX specimens were diagnostic in 85% of black patients and 38% of white patients (p = 0.00081), but diagnostic yield did not correlate with patient's sex, symptoms, radiographic stage of disease, or extent of physiologic abnormalities. Four patients with normal-appearing bronchial mucosa underwent EBBX, and sarcoidosis was diagnosed in two. Transbronchial lung biopsy (TBBX) specimens were diagnostic of sarcoidosis in 61 of 82 (74%) black and 28 of 56 (50%) white patients (p = 0.0038). We conclude that the bronchial mucosa appears abnormal in the majority (55%) of patients with sarcoidosis. EBBX specimens will diagnose sarcoidosis in a high percentage of such patients and should be performed routinely. EBBX may be preferable to TBBX because of its greater safety profile. In our patients, the yield of both EBBX and TBBX was significantly greater in African-Americans than white Americans.

Immunologic basis for the redefinition of malignant lymphomas.

As neoplasms of the immune system, lymphomas can be characterized by a variety of immunologic technics. These technics, used in conjunction with morphology and cytochemistry, have promoted the development of lymphoma classifications which relate more closely to our current understanding of the anatomy and function of the immune system than earlier classifications. This brief review of the development and function of the immune system and discussion of technics used in distinguishing B and T lymphocytes is intended to provide background and perspective for the other papers presented in this symposium.