I-J has been defined as a locus mapped in the murine major histocompatibility complex (MHC) which encodes serological markers found primarily on the surface of suppressor T cells (TS) and soluble suppressor factors (TSF). Recent studies have, however, revealed that there is no such specialized locus within the MHC at the DNA level. As the existence of I-J determinants at the protein level on functional T cells, T-cell clones and hybridomas has been confirmed by several serological and biochemical studies, this contradiction has raised serious arguments in the immunological community concerning the nature, origin and expression of I-J determinants. We have raised a number of monoclonal antibodies against the polymorphic structure of I-J molecules, and have studied the expression of I-J epitopes on T cells derived from irradiated bone marrow chimaeras in which stem cells of different genotype differentiated into T cells under the foreign host MHC environment. The results, presented here, indicate that I-J epitopes are not primarily determined by the MHC genes of the stem cells themselves, but are adaptively acquired by T cells differentiated in the chimaeric condition according to the environmental MHC phenotype. Thus, the serologically detectable I-J epitopes are found to be associated with inducible T-cell receptors recognizing self class II MHC antigens.

Animals↗

PubMedDate not supplied

A reappraisal of Mls genetics.

Although the minor lymphocyte stimulatory locus (Mls) system was originally described as a single-locus, multiple-allelic system, allelism among the genes which encode Mlsa, Mlsc and Mlsd has not been demonstrated formally. In this report, genetic linkage between genes encoding Mlsa and Mlsc was studied by testing responses of unprimed T cells, as well as Mlsa- and Mlsc-specific T cell clones, to the progeny of (AKR/J x C3H/HeJ) F1 x B10.BR [(Mlsa x Mlsc)F1 x Mlsb] crosses. In addition, the configuration of Mls genes expressed by CBA/J (Mlsd) was evaluated by examining the response pattern of a panel of Mlsd-specific clones to (CBA/J x B10.BR)F1 x B10.BR stimulators. Results of these segregation analyses indicated that the Mls system is composed of at least two independent and unlinked genes which encode, respectively, the determinants identified as Mlsa and Mlsc.

Alleles↗

PubMedDate not supplied

Mls determinants recognized by T cells.

The relationship among different minor lymphocyte stimulatory locus (Mls) determinants, Mlsa, Mlsb, Mlsc and Mlsd, remains unclear. Because of the high degree of cross-reactivity between Mlsa and Mlsd determinants, the weak stimulatory capacity of Mlsc, and the generally non-stimulatory nature of Mlsb, some investigators have recently suggested that Mls is composed of only a single expressed allele originally defined as the a and d alleles. In order to clarify the nature of Mls determinants, T cell clones positively selected for reactivity to the three stimulatory Mls determinants, Mlsa, Mlsc and Mlsd, were generated and their specificities defined by extensive genetic studies. The response pattern of these Mls-specific clones as well as the results of primary mixed lymphocyte responses indicated that: (i) Mlsa and Mlsc determinants recognized by T cells are distinct, demonstrating that polymorphism does exist within the Mls system; and (ii) Mlsd is not an independent Mls type since Mlsd determinants are composed of Mlsa and Mlsc determinants and anti-Mlsd T cell responses are, in fact, the sum of anti-Mlsa and anti-Mlsc responses.

Alleles↗

PubMedDate not supplied

Genetic relationships of Mlsa among polymorphic loci on distal mouse chromosome 1.

The segregation of Mlsa with respect to genes localized distally on mouse chromosome 1 was examined in two sets of recombinant inbred (RI) strains. In order to localize Mlsa, a linkage map based on analysis of both interspecific backcross mice and multiple sets of RI strains was utilized: (centromere) - Ren-1,2 - 10 centimorgans (cM) - At-3 - 8cM-Apo-A2/Ly-17 - 2cM - Spna-1 - 4cM - Akp-1 - (telomere). The Mlsa allele was mapped to a region that extended just centromeric of Ly-17 (one crossover in 40 RI strains) to just telomeric of Spna-1 (no crossover in 40 RI strains). The identification of multiple polymorphic loci in the region of Mlsa should allow precise gene localization and assist in efforts to clone this gene.

Alleles↗

PubMedDate not supplied

Evaluation of MTT assay in agarose for chemosensitivity testing of human cancers: comparison with MTT assay.

The MTT assay in agarose, a simple colorimetric test performed in double-layer agarose, has been evaluated for chemosensitivity testing of fresh tumor samples from human cancers in comparison with the MTT assay. The absorbance of cells from fibroblast cell lines or normal tissues was markedly reduced in agarose. The chemosensitivity of cells from a carcinoma cell line or fresh tumor tissues was not apparently affected by the presence of almost 50% of fibroblast or nonmalignant cells in the MTT assay in agarose, whereas it did so in the MTT assay. The frequency of the differences between chemosensitivity of fresh tumor samples in both assays was increased, when the tumor tissue cells contained a higher proportion of nonmalignant cells, i.e. vimentin-positive cells. In 173 patients with various carcinomas, in vitro sensitivity to 7 drugs in the MTT assay in agarose was significantly greater than that in the MTT assay. Further, the MTT assay in agarose had a higher accuracy for prediction of either sensitivity or resistance than the MTT assay in a total of 38 in vitro-in vivo correlations. These results indicated that the MTT assay in agarose was a more suitable technique for the application to chemosensitivity of fresh tumor samples from patients with various carcinomas as compared to the MTT assay.

Adult↗

PubMedDate not supplied

Increased uptake and prolonged retention of actinomycin D by concomitant hyperthermia related to cytotoxic enhancement.

We investigated the possible mechanisms of hyperthermic enhancement of actinomycin D (AMD) cytotoxicity in a neoplastic cell line. The hyperthermic enhancement of AMD cytotoxicity depended on both the temperature and the sequence of the administration. The percentage survival of simultaneous treatment of either 42 or 43 degrees C hyperthermia with 5 micrograms/ml AMD was 42% or 2.2%, respectively, and the amount of AMD in the DNA (DNA-bound AMD) of simultaneous hyperthermia at either 42 or 43 degrees C was 16.5 or 27.2 ng/10(6) cells, respectively. The percentage survival of sequential treatment of 5 micrograms/ml AMD following either 42 or 43 degrees C hyperthermia was 55 or 46%, respectively. The amount of DNA-bound AMD of sequential hyperthermia at either 42 or 43 degrees C was 10.8 or 21.7 ng/10(6) cells, respectively. In addition, the percentage survivals of the S-phase and G1-phase cells concomitantly treated with 43 degrees C hyperthermia and 5 micrograms/ml of AMD were 1.4 and 92%, respectively, and the amounts of DNA-bound AMD of these S-phase and G1-phase cells were 28.2 and 1.6 ng/10(6) cells. These findings suggested that an increased amount of AMD in DNA was responsible for the hyperthermic enhancement of AMD cytotoxicity. When the G1-phase cells were treated with 5 micrograms/ml AMD alone, without hyperthermia, the amount of AMD in acid-soluble fraction of the G1-phase cells was quite low (0.3 ng/10(6) cells). However, concomitant hyperthermia treatment with AMD at the G1-phase significantly increased the AMD amount (1.6 ng/10(6) cells at 42 degrees C, and 3.1 ng/10(6) cells at 43 degrees C) up to a level equal to that in asynchronous (1.7 ng/10(6) cells) and S-phase cells (2.1 ng/10(6) cells) simultaneously treated with hyperthermia and AMD. It was suggested that hyperthermia altered the membrane permeability of the G1-phase cells. The increase of the AMD amount in the DNA might thus be the result of higher intracellular drug concentration.

Animals↗

PubMedDate not supplied

The role of bcl-2 expression in breast carcinomas (Review).

The proto-oncogene bcl-2 is demonstrated to block a final common pathway leading to apoptosis and is expressed in more than half of human breast cancers. Invasive breast cancer has reduced bcl-2 immunostaining compared with normal breast epithelia and preinvasive breast lesions. As an inhibitor of apoptosis, bcl-2 should correlate with highly aggressive tumor biology and resistance to hormonal/cytotoxic therapy. However, high bcl-2 expression has been shown to associate with a number of favorable prognostic factors including ER positivity, PgR positivity, low histological grade, well-differentiated tumor, absence of c-erbB-2 and p53. Unexpectedly, numerous studies have shown that tumors with high bcl-2 expression are more responsive to hormone therapy and have more favorable disease-free and overall survival. The clinical significance of bcl-2 in tumorigenesis and prognosis of breast carcinomas from the data recently published are reviewed. Its role in modulation of hormonal/cytotoxic therapy and future directions are also discussed.

Breast↗

PubMedDate not supplied

Enhancement of cytotoxicity by hyperthermia after a long-term culture with 5-fluorouracil in transformed cells.

The cytotoxic effect of 5-FU (5-fluorouracil) was demonstrated to be enhanced by hyperthermia after treatment with 5-FU at even a comparatively low dose over fairly long periods. The cytotoxic effect of the combined treatment with 42 degrees C-hyperthermia and 1 microgram/ml 5-FU for 48 hrs, the cytotoxic effect of 42 degrees C-hyperthermia and 5 micrograms/ml 5-FU for 24 hrs, and the cytotoxic effect of 43 degrees C-hyperthermia and 1 and 5 micrograms/ml 5-FU for 8 hrs were studied. The maximally enhanced rate of 42 degrees C-hyperthermia after 5-FU treatment for 96 hrs was 48% after a 1 microgram/ml 5-FU treatment and 150% after 45 hrs with the 5 micrograms/ml 5-FU treatment. The maximally enhanced rate of 43 degrees C-hyperthermia after 5-FU treatment was 170% after 45 hrs with 1 microgram/ml 5-FU treatment and 180% after 24 hrs with 5 mg/ml 5-FU treatment. When V-79 cells were treated at the same temperature, the maximally enhanced rate with 1 microgram/ml 5-FU was almost equal to that of 5 micrograms/ml. Moreover, when each maximally enhanced rate was equalized, each concentration of FU (RNA)/RNA practically became equal, i.e., when the maximally enhanced rates were approximately 150 and 170-180%, FU (RNA)/RNA concentrations were about 40 and 15 ng/mg RNA, respectively. We thus concluded that FU (RNA)/RNA concentration might play an important role as an indicator of the effect of the combined treatment of 5-FU and hyperthermia.

Animals↗

PubMedDate not supplied

Cost effectiveness of radiofrequency catheter ablation versus medical treatment for paroxysmal supraventricular tachycardia in Japan.

This study evaluated the cost of performing radiofrequency catheter ablation in Japanese patients with paroxysmal supraventricular tachycardia refractory to antiarrhythmic drug therapy in comparison with the cost of continuing pharmacologic treatment. Twenty patients (mean age 44 +/- 14 years) underwent successful ablation: 15 patients with Wolff-Parkinson-White syndrome and five with atrioventricular nodal reentrant tachycardia. The mean duration of symptoms was 77 +/- 60 months. The patients had been treated with 2.6 +/- 1.7 antiarrhythmic drugs before undergoing ablation. Charges derived from hospital bills were compared with the outpatient charges for the year before ablation. The mean hospital stay for the ablation procedure was 4.3 +/- 0.5 days. The mean total charge for ablation was 982,806 yen +/- 103,195, and 5.7 +/- 0.7 times the outpatient charges in the previous year. The majority of radical cure charges were the costs of the electrode catheters used in the ablation procedure. All patients had a successful outcome and required no additional antiarrhythmic drug therapy. If medical treatment were continued without ablation, the mean total life-expectancy charges were estimated at 7,064,726 yen +/- 3,116,621, 41.0 +/- 19.2 times the outpatient charges. The total life charges of medical treatment were significantly more than the total ablation charges (p < 0.001). This study suggests that radiofrequency catheter ablation is of clinical benefit in treating paroxysmal supraventricular tachycardia, and markedly reduces the cost of definitive therapy. This strategy appears to be more economical than pharmacologic treatment.

Adult↗

PubMedDate not supplied

Squamous cell carcinoma of the breast. Report of a case diagnosed by fine needle aspiration cytology.

A 66-year-old woman presented with pure squamous cell carcinoma of the breast, a rare occurrence. The incidence of pure squamous cell carcinoma of the breast is lower than that of the mixed type. The preoperative diagnosis could be made by fine needle aspiration cytology. A modified radical mastectomy was performed. The patient was doing well, with no evidence of recurrence, 17 months after surgery.

Aged↗

PubMedDate not supplied

Prognostic value of nuclear grading assessed by image cytometry for node negative breast cancer patients.

BACKGROUND: Although nuclear grading is a useful prognostic factor for node-negative breast cancer, it is difficult to evaluate objectively. In this study, we show the heterogeneity of the nuclear area (NA), and predictive value of NA evaluated by image cytometry. MATERIALS AND METHODS: The NA of over 100 cancer cell nuclei were measured by two types of image cytometer on 182 primary lesions of node negative (nO) breast cancer patients. The mean NA of invasive and intraductal cells were measured on separated regions. The nuclei for evaluation were selected using three different methods: all cells, invasive cells alone, and larger cells. The prognoses were compared after the cases were divided at mean + SD/2. RESULTS: No differences were observed in the mean NA of each portion. The difference of disease free survival between the two subgroups by log rank test and the p-value of each method were, 0.82, 0.21 and 0.0076. CONCLUSIONS: Only when larger nuclei were selected, was NA a significant prognostic factor for node negative breast cancer patients. The cancer cells with larger nuclei possibly represent the malignant potential of each case.

Breast Neoplasms↗

PubMedDate not supplied

Apoptotic index correlates to bcl-2 and p53 protein expression, histological grade and prognosis in invasive breast cancers.

Apoptosis is considered to play a critical role in tumorigenesis. In order to clarify the significance of apoptosis in breast cancers, we quantitated apoptotic cells by light microscopy in 126 patients with invasive breast cancers. The expression of bcl-2, and p53, as regulators of apoptosis, was immunohistochemically analyzed. Apoptotic index (AI) detected in the patients ranged from 0 to 48 per mm2 of breast cancer cells (mean +/- SE, 11.0 +/- 0.97). Significantly highly AI was found for the tumors with grade 3 (p < 0.0001), high mitotic index (p < 0.0001), and bcl-2 negatively (p = 0.004) compared with those with grade 1 or 2, low mitotic index, and bcl-2 expression, respectively. Moreover, high AI was associated with larger tumor size (p = 0.008), positive lymph nodes (p = 0.01), p53 positivity (p = 0.01), and advanced TNM stage (p = 0.03). In survival analysis, we found that low AI, like bcl-2 and other conventional prognostic indicators, was significantly predictive of better prognosis in terms of both disease-free survival (DFS) and overall survival (OS) (each, p < 0.0001). In multivariate analysis, AI failed to retain an independent significant value for DFS or OS. Our results indicate that low AI is related to a number of clinicopathologic and biologic parameters known to predict a lower risk of recurrence and is associated with a favourable survival in invasive breast cancer. However, it was not an independent prognostic factor for clinical outcome in this patient series.

Apoptosis↗