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Biomedical subjects

J T Manning

Publications and source records attributed to J T Manning.

At least 73 records · Page 4Linked to original sources

A morphologic, immunologic, and cytometric approach to the classification of non-Hodgkin's lymphoma in effusions.

The biologic and clinical heterogeneity of the various subtypes of non-Hodgkin's lymphoma is related to differences in morphologic, immunologic, and kinetic properties. Comprehensive studies characterizing these features in lymphomatous effusion have yet to be reported. We recently studied 27 effusion specimens from 26 patients with clinically suspected or confirmed lymphoma. Wright-Giemsa- and Papanicolaou-stained cytologic preparations, acridine orange nucleic acid flow cytometry, and immunoperoxidase staining of cell suspensions using antibodies to a battery of T and B cell markers were evaluated and compared with prior histologic accessions. Specimens were classified by cytologic characteristics according to the International Working Formulation Scheme and by acridine orange nucleic acid flow cytometry using the parameters of DNA, RNA, and proliferative activity. Correlation of the cytometric and morphologic data demonstrated that with increasing cytologic grade of lymphoma, the proliferative activity increased progressively and distinguished between grades (P less than 0.01). Immunologic studies identified B cell phenotype in 16 specimens, T cell in three, and true histiocytic lymphoma in one; one lymphoma had no cell markers (null cell). Six effusions proved to be inflammatory and reactive according to surface marker studies. Classification by cytologic characteristics showed good correlation with histologic classification performed previously. Immunologic study of cytologic specimens gave results identical to those achieved by frozen-section immunohistologic examination. Thus, immunologic and cytometric parameters can be readily performed on effusion specimens and aid in the diagnosis and classification of lymphomas.

Adult↗

Necrotizing sialometaplasia of major salivary glands.

Major salivary glands have been rarely reported as sites of necrotizing sialometaplasia, a disease primarily affecting minor salivary tissue, particularly that of the palate. Eight cases of necrotizing sialometaplasia of the parotid and submandibular glands are presented and added to six reported earlier by Donath (1979). The clinical and pathologic findings in the 14 cases give strong support to the vascular-based-infarct genesis of necrotizing sialometaplasia.

Adolescent↗

Granulocytic sarcoma in nonleukemic patients.

Sixteen patients presenting with granulocytic sarcoma without evidence of acute leukemia were seen and diagnosed at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1962 to 1985. Seven of them (44%) did not develop acute leukemia. Of these seven, four are alive with no evidence of disease 3.5 to 16 years after initial presentation; the remaining three patients died of their disease within 2 to 8 months of presentation. Two of 16 patients were diagnosed within the last 15 months and do not have adequate follow-up. The seven remaining patients developed acute leukemia within 1 week to 13 months of the diagnosis of granulocytic sarcoma. Six of them died 5 weeks to 16 months after diagnosis; one patient has been in complete remission for 8 years. Twelve of these 16 cases (75%) were initially misdiagnosed, most frequently as large cell lymphoma. The remaining four cases were correctly diagnosed as granulocytic sarcoma. The naphthol-ASD-chloroacetate esterase stain was required to make the correct diagnosis in all cases. Contrary to findings in other series, granulocytic sarcoma arising in nonleukemic patients does not necessarily progress to acute leukemia. At least four of 16 (25%) patients in this series did not develop acute leukemia during the 3.5 to 16 years they have been followed. No prognostic factors were identified in this series to predict which patients would develop acute leukemia and which ones would not.

Adolescent↗

Chromosomal abnormalities in lymphoma and their correlations with nucleic acid flow cytometry.

Cytogenetic studies were performed on 25 samples obtained from 25 patients with lymphoma. Fourteen of these were also simultaneously studied with nucleic acid flow cytometry to determine percent S-phase and DNA content (ploidy). In 17 cases (68%), evaluable metaphases were obtained. The evaluable metaphase rate was higher in previously untreated patients (15/19 or 79%). All but two cases showed abnormal karyotype. All five cases showing either the t(8;14) or t(8;22) abnormality were associated with extremely high percent S-phase values, ranging from 36% to 47%, which is in the range of high-grade lymphomas according to our previous experience. Four of these cases were diagnosed as Burkitt's lymphoma and one as diffuse large cell lymphoma. Further review of this latter case resulted in the pathologic diagnosis being changed to Burkitt's lymphoma. Three patients had either numerical or structural abnormalities of chromosome #21 [two cases of extra chromosomes and one i(21q)]. All three cases were diagnosed as diffuse large cell lymphoma. Four instances of trisomy 12 were identified. Only one of these was diagnosed as diffuse well-differentiated lymphocytic lymphoma. The remaining three were Burkitt's lymphoma in two and diffuse large cell lymphoma in one. Two instances of t(14;18) were observed. This is the characteristic abnormality of follicular lymphomas. One of these cases was a follicular large cell lymphoma. The second case had possibly originated from a follicular mixed lymphoma and had evolved into a diffuse mixed cell type. Both of these cases had low S-phase values in the range of low-grade lymphomas. The correlation between ploidy as determined by flow cytometry and cytogenetic analysis was good whenever the DNA index was elevated. However, when the DNA index was 1.0 (diploid), concordant measurements were observed in only five of eight cases. Flow cytometry detected one instance of clearly abnormal ploidy, which was thought to be diploid by cytogenetics. This case most likely represents a "false negative" cytogenetic determination.

Adolescent↗

Environmental change, mutational load and the advantage of sexual reproduction.

There is evidence that asexual reproduction has a long-term disadvantage when compared to sexual reproduction. This disadvantage is usually assumed to arise from the more efficient incorporation of advantageous mutations by sexual populations. We consider here the effect on asexual and sexual populations of changes in the fitness of harmful mutations. It is shown that the re-establishment of equilibrium following environmental change is generally faster in sexual populations, and that the mutational load experienced by the sexual population can be significantly less during this period than that experienced by an asexual one. Changes in the fitness of harmful mutations may therefore impose a greater long-term disadvantage on asexual populations than those which are sexual.

Animals↗

T-cell involvement in benign phase chronic myelogenous leukemia.

T cells from the peripheral blood of patients with chronic myeloid leukemia (CML) were cultured with phytohemagglutinin and T-cell growth factor (TCGF) in agar culture. These T-cell colonies were pooled and expanded further in liquid culture with TCGF and then simultaneously analysed for the E-rosette receptor with the monoclonal antibody OKT11 and for the presence of the Philadelphia (Ph1) chromosome. OKT11 analysis showed these populations to be composed 99.5% or more of T cells. In four of the seven patients the T-cell suspension showed 7/50 (14%), 3/36 (8%), 2/34 (6%), and 4/44 (9%) Ph1 metaphases. Furthermore, Ph1 metaphases were demonstrated in T-cell cultures in two patients when bone marrow metaphases simultaneously showed 90 and 100% Ph1 negative metaphases secondary to human leukocyte interferon therapy or combination chemotherapy. A minority of T cells in benign phase CML have the Ph1 abnormality despite reduced number of Ph1 metaphases in bone marrow from therapy.

Adult↗

Extraosseous osteogenic sarcoma of the parotid gland.

The first reported case of an extraosseous osteogenic carcinoma of the parotid gland is presented. The head and neck region is an unusual site for these unusual neoplasms, with approximately 5 per cent of all extraosseous osteogenic sarcomas originating in the soft tissues of the face and neck. The neoplasms may arise after a latent period following radiation therapy. The majority, however, arise de novo. As a group, extraosseous osteogenic sarcomas are very aggressive and lethal neoplasms with an average 5-year survival of 15.6 per cent (Rao et al., 1978).

Aged↗

Comparison of monoclonal and polyclonal antibodies directed against immunoglobulin light and heavy chains in non-Hodgkin's lymphoma.

A study comparing the usage of monoclonal and polyclonal antibodies specific for immunoglobulin light and heavy chains was performed on frozen-tissue sections of 30 B-cell non-Hodgkin's lymphomas. In 16 cases, monotypic staining for an immunoglobulin light chain was demonstrated with monoclonal antibodies using a three-step avidin-biotin peroxidase complex (ABC) method; 13 cases were positive for kappa. In 14 cases, no immunoglobulin light-chain production was demonstrated. Repeat staining of 11 of these 14 cases with polyclonal anti-sera by a direct immunoperoxidase method demonstrated monotypic staining for light chain in 10 cases, 9 of which were positive for lambda. In 22 of 30 non-Hodgkin's lymphomas, an immunoglobulin heavy chain was identified using monoclonal anti-sera. In eight cases, however, no heavy chain was found. Repeated staining with polyclonal sera of additional sections in three of eight cases demonstrated heavy-chain production in each case. Decreased sensitivity, especially for the detection of the lambda light chain, rendered this particular lot of monoclonal antibodies unsuitable for immunophenotyping non-Hodgkin's lymphomas. Variability of antigenic sites on the immunoglobulin molecule seems a likely explanation for these observations.

Antibodies, Monoclonal↗

Tumor burden assessment and its implication for a prognostic model in advanced diffuse large-cell lymphoma.

Previously untreated adult patients who presented with advanced diffuse large-cell lymphoma (DLCL) at diagnosis were studied to identify possible prognostic factors. One hundred five patients were seen between 1974 and 1981; 45 patients were stage III and 60 patients were stage IV. All patients received cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo). Stage III patients also received radiation therapy alternated with chemotherapy. Overall survival was 50% at 5 years and 43% at 8 years. Seventy-four patients achieved a complete remission (CR) and 37 are alive and disease-free with a median follow-up of 72 months. There was no difference in clinical outcome between stage III and stage IV. However, a proportional hazards model identified lactic dehydrogenase (LDH) level and tumor burden, among all clinical factors studied, as independent risk factors for survival. These two factors were also important for achievement of remission and relapse-free survival. Three distinct patient risk groups were identified with 5-year survival rates of 87%, 48%, and 20%, respectively. The measure of tumor burden proposed herein, along with LDH level, can be used for developing treatment programs, and for meaningful comparison of different treatment regimens, as well as assessment of prognosis.

Abdominal Neoplasms↗

Soft tissue tumors: unusual forms.

A variety of soft tissue tumors can occur in the head and neck area. Because, with the possible exception of rhabdomyosarcoma, they are seen less often in these sites than in the trunk and extremities, they can pose special problems in diagnosis, classification, and management.

Adolescent↗

Mate choice, monogamy and mutational load.

The classical Haldane mutational load for dominant mutations is 1 - e-alpha (where alpha = the mutation rate of the genome). This is independent of the fitness of the mutant heterozygotes. As alpha may be between 0.9 and 1.8 this may be too high for low fecundity species to bear. The load may be greatly reduced for mildly deleterious mutations if female choice (for males with few or no mutations) is present in a polygamous species. It is shown here that if females and males prefer partners with few or no mutations then the load may also be reduced in monogamous species. As in the polygamous model the effect is greatest if mutations are mildly deleterious.

Animals↗

Argentaffin endocrine carcinoma (carcinoid) of the pancreas with concomitant breast metastasis: an immunohistochemical and electron microscopic study.

A pancreatic carcinoid tumor that metastasized to the breast is reported. The breast tumor was originally diagnosed as adenocarcinoma of the breast. Silver impregnation revealed the presence of argentaffin cytoplasmic granules. Immunocytochemical studies demonstrated immunoreactivity for serotonin but not for lactalbumin, a marker for breast epithelial cells. These features, together with the electron microscopic observation of pleomorphic secretory granules, permitted recognition of the tumor as metastatic carcinoid. This report illustrates the importance of the combined histochemical, immunocytochemical, and electron microscopic studies of breast tumors with a carcinoid pattern.

Adult↗

Stage IV diffuse large-cell lymphoma: a long-term analysis.

A long-term analysis of the clinical outcome of previously untreated adult patients who presented with stage IV diffuse large-cell lymphoma at diagnosis was performed to identify possible prognostic factors. Sixty-one patients were seen between 1974 and 1981; all were treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin followed by cyclophosphamide, vincristine, prednisone, and bleomycin for a total of one year. Overall five-year survival was 48.5%, with a median follow-up of 53 months. Of the 56 patients evaluable for remission status, 41 achieved a complete remission, and 27 are alive and disease free. Clinical factors of prognostic importance for survival included age, constitutional symptoms, lactate dehydrogenase (LDH) level, presence of mediastinal disease, large-cell infiltration of bone marrow, and number of extranodal sites of disease. The proportional hazards model then identified age, number of extranodal sites, and, to a lesser extent, serum LDH level as independent risk factors for survival. Four distinct patient risk groups were identified using these three factors. Younger patients with only one extranodal site of disease and normal LDH levels responded well on this therapy, with 100% alive at five years. In contrast, survival was less than 30% at five years for patients in the lowest risk group. There were 11 relapses; LDH level, constitutional symptoms, and mediastinal disease predicted for relapse. Knowledge of these risk factors permits individualization of treatment planning and allows more meaningful comparisons with the results of treatment studies using other intensive regimens.

Adult↗

Crystals and alpha-1-antitrypsin-reactive globoid inclusions in an islet cell tumor of the pancreas.

An islet cell tumor of the pancreas with unusual light microscopic, ultrastructural, and immunocytochemical features is reported. In addition to secretory granules and positive immunostaining for pancreatic polypeptide, the tumor contained globoid intracytoplasmic inclusions by light and electron microscopy, which correlated with a positive immunoreaction for alpha-1-antitrypsin, and Reinke-like crystals.

Adenoma, Islet Cell↗

Bronchioloalveolar carcinoma: The significance of two histopathologic types.

A review of the pathologic material from 34 patients having bronchioloalveolar carcinoma has demonstrated two histopathologic types that have a bearing on the prognosis. Type 1 is associated with gross and microscopic mucus production, and is likely to be multicentric. Type 2 has lesser amounts of mucus, and is likely to be solitary. The 5-year survival of type 1 is 26%, and that of type 2 is 72%.

Adenocarcinoma, Bronchiolo-Alveolar↗

Males and the advantage of sex.

Most sexual populations are at a two-fold disadvantage to parthenogenetic populations. This is because males are produced in equal numbers to females and males contribute virtually no food supplies to the zygote. Females therefore "waste their energy" in the production of sons. Parthenogenetic females produce only daughters and therefore have a two-fold advantage. It is argued that female choice (of males) and male: male competition can reduce mutational loads and this may compensate for the two-fold disadvantage of males. The Haldane mutation load principle indicates a load of 2mu, where mu is the mutation rate per gamete. Female choice and male: male competition are capable of reducing this substantially. The effect is greatest with mildly deleterious mutations and is therefore dependent on the fitness of the mutations. This is in contrast to the Haldane principle load which is determined by the mutation rate only. As most mutations appear to be mildly deleterious the load in many sexual populations may be substantially below that indicated by the Haldane principle.

Animals↗

Combined modality therapy in Stage III and Stage IIIE diffuse large cell lymphomas.

Combined modality therapy consisting of CHOP-Bleo (cyclophosphamide, Adriamycin [doxorubicin], vincristine (Oncovin), prednisone, and bleomycin) and limited-field radiotherapy was given to 47 patients with Stage III and IIIE diffuse large cell lymphomas. Overall 5-year survival and disease-free survival figures are 64% and 53%, respectively. Twenty-nine patients achieved and maintained a complete remission during treatment; 92% of these patients are alive at 5 years, and 87% are disease-free. Prognostic factors were assessed for the entire group. Age, "B" symptoms, extranodal involvement, and extensive abdominal involvement had little effect on survival. However, the presence of mediastinal involvement and extensive abdominal involvement was associated with a poor response rate and survival.

Abdominal Neoplasms↗