Breast metastases from lung carcinomas: a report of three cases.

Tumours metastasising to the breast are very infrequent, with an incidence of 0.4-6.6% of all breast tumours. Occasionally a breast mass is the first indicator of a tumour arising elsewhere. Development of metastases to the breast from a lung cancer is very rare and the prognosis for such patients is poor. We present three patients who had metastases to the breast presenting clinically as the primary origin. It is important to distinguish a primary breast cancer from a metastasis, as different therapies are offered with considerably different outcomes.

Intra- and extracellular reactive oxygen species generated by blue light.

Blue light from dental photopolymerization devices has significant biological effects on cells. These effects may alter normal cell function of tissues exposed during placement of oral restorations, but recent data suggest that some light-induced effects may also be therapeutically useful, for example in the treatment of epithelial cancers. Reactive oxygen species (ROS) appear to mediate blue light effects in cells, but the sources of ROS (intra- versus extracellular) and their respective roles in the cellular response to blue light are not known. In the current study, we tested the hypothesis that intra- and extracellular sources of blue light-generated ROS synergize to depress mitochondrial function. Normal human epidermal keratinocytes (NHEK) and oral squamous cell carcinoma (OSC2) cells were exposed to blue light (380-500 nm; 5-60 J/cm(2)) from a dental photopolymerization source (quartz-tungsten-halogen, 550 mW/cm(2)). Light was applied in cell-culture media or balanced salt solutions with or without cells present. Intracellular ROS levels were estimated using the dihydrofluorescein diacetate (DFDA) assay; extracellular ROS levels were estimated using the leucocrystal violet assay. Cell response was estimated using the MTT mitochondrial activity assay. Blue light increased intracellular ROS equally in both NHEK and OSC2. Blue light also increased ROS levels in cell-free MEM or salt solutions, and riboflavin supplements increased ROS formation. Extracellularly applied ROS rapidly (50-400 muM, <1 min) increased intracellular ROS levels, which were higher and longer-lived in NHEK than OSC2. The type of cell-culture medium significantly affected the ability of blue light to suppress cellular mitochondrial activity; the greatest suppression was observed in DMEM-containing or NHEK media. Collectively, the data support our hypothesis that intra- and extracellularly generated ROS synergize to affect cellular mitochondrial suppression of tumor cells in response to blue light. However, the identity of blue light targets that mediate these changes remain unclear. These data support additional investigations into the risks of coincident exposure of tissues to blue light during material polymerization of restorative materials, and possible therapeutic benefits.

A fluorescein-linked immunoabsorbent assay for the detection of antibacterial antibodies in secretions and serum.

A rapid, quantitative solid-phase immunofluorescence assay has been developed to measure antibodies reactive with Streptococcus mutans in saliva and serum. Formalin killed bacteria were adsorbed to cellulose acetate discs and antibodies bound to the antigen-coated immunoabsorbent were detected by use of fluorescein-labeled antibody to human immunoglobulin isotypes. Quantitation was performed by placing the immunoabsorbent discs in a fluorometer. Low levels of naturally occurring antibodies reactive with S. mutans were easily detected in saliva and serum from normal human subjects.

Chemotherapy of hormone-refractory carcinoma of prostate with 5-fluorouracil, adriamycin, and mitomycin C.

A modification of the DMF protocol was used to treat 14 patients with hormone-refractory adenocarcinoma of the prostate. A subjective response of pain relief occurred in 71 per cent (10/14) of the patients. The median duration of the response in these patients was 4.2 months, and their median survival was 248 days. No patient experienced either an objective complete or partial response based on the criteria of the NPCP. However, an objective stable response was produced in 36 per cent (5/14) of the patients, and their median survival was 330 days. Patients entering the study with a performance status of less than or equal to 2 exhibited a longer median survival than patients with a performance status greater than 2. This regimen of 5-fluorouracil, doxorubicin (Adriamycin), and mitomycin C is reasonably well tolerated and appears to warrant consideration as a palliative therapeutic alternative in hormone-resistant prostate cancer.

Antigens of Streptococcus mutans implicated in virulence--production of antibodies.

The present studies assayed antibody activities in serum and saliva of animals immunized by different routes, with cells of S. mutans or cell-free preparations containing GTF, FTF, LTA and/or dextranase synthesized by S. mutans. The results show that the type of immunogenic preparation and the route of its administration can elicit different antibody response and may in part explain the disparity of results achieved by different investigators. The results further emphasize the need to use standardized preparations and carefully described protocols for vaccination.

Guidewire assisted cephalic vein cutdown for insertion of totally implantable access ports.

BACKGROUND: Totally implantable access ports (TIAP) placed by the cephalic vein cutdown technique have high failure rates. METHODS: We describe a guidewire assisted technique of the cephalic vein cutdown for TIAP placement that can be easily introduced catheter when difficulties in insertion of the catheter. The key point of the presented technique is the use of J guidewire to go beyond the stenosis and advancement of catheter through the guidewire into the superior vena cava. RESULTS: We used this technique for introducing the catheter in six patients without failure or complication. CONCLUSION: The presented technique is easy and simple. It can be used where there are difficulties in insertion of the catheter by cephalic vein cutdown method.

Structural integrity of host defense factors in dental plaque.

The structural integrity of immunoglobulin A (IgA), IgG, and IgM and lactoferrin in dental plaque fluid samples from two populations of Colombian children with contrasting levels of dental caries was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electrophoretic transfer to nitrocellulose. The immune factors or their fragments or both were detected with monospecific antibody conjugated with horseradish peroxidase. All the immune factors examined were extensively degraded, although there appeared to be small amounts of intact IgA and IgG in some samples. Analysis of the samples with antibody to secretory component showed that secretory IgA as well as serum IgA was degraded. IgG appeared to be cleaved into two major fragments, one fragment having a relative mobility similar to the F(ab')2 fragment of IgG and the other a relative mobility slightly greater than Fc. IgM and lactoferrin were virtually completely degraded. There was no apparent relationship between the fragmentation patterns of IgA and IgG in the plaque fluid samples from the two communities and their susceptibility to dental caries.

Case report of vasopressin-responsive diabetes insipidus associated with chronic myelogenous leukemia.

A sixth case in the world literature is reported of a 59-year-old male with diabetes insipidus (DI) associated with chronic myelogenous leukemia (CML). The patient is unique in that his CML was diagnosed 10 years before he presented with vasopressin-responsive DI. Radiation to the central nervous system failed to reduce the daily requirement of his need for vasopressin.

Maternal malnutrition does not affect fetal hepatic glycogen synthase ontogeny.

Maternal malnutrition late in pregnancy results in the reduced storage of fetal hepatic glycogen in the final days of gestation and an accentuation of normal birth-related hypoglycemia. It was of interest to determine whether or not low glycogen levels resulted when maternal malnutrition disrupted the normal ontogeny of fetal hepatic glycogen synthase, an important glycogenic enzyme. A defect in this enzyme would be expected to seriously affect prenatal and postnatal glycogen synthesis. For this study, livers were removed from fetuses from malnourished (50% of normal dietary intake) mice, as well as from ad libitum-fed mice, and used for the determination of hepatic glycogen, glycogen synthase activity, and glycogen synthase protein levels. In this paper we report that maternal dietary restriction late in pregnancy produces growth-retarded fetuses with severely reduced hepatic glycogen levels, but the normal ontogenic changes in the quantity and activity of hepatic glycogen synthase were not affected. It is especially significant that the accumulation of glycogen synthase occurred despite the minimal level of natural substrate available for the enzyme. These results suggest that the accumulation and activity of hepatic glycogen synthase during late gestation is related to developmental events rather than levels of substrate or glycogen.

Acute leukemia following combination chemotherapy for cancer of the lung.

A 64-year-old male with recurrent metastatic squamous cell carcinoma was successfully treated with intensive combination chemotherapy. His complete remission was maintained with a nitrosourea, nitrogen mustard and methotrexate for 3 years. While in remission the patient developed acute leukemia. It appears that this secondary malignancy was due to his prolonged chemotherapy.

Peutz-Jeghers syndrome with intestinal carcinoma: report of the association in one family.

The Peutz-Jeghers Syndrome is a rare, genectically inherited disorder. There are insufficient data to establish this syndrome as a precancerous condition, but documented cases of gastrointestinal cancer arising in this syndrome have been reported with an incidence of 2--3%. Since the syndrome is transmitted as an autosomal dominant and is associated with cancer, family members so afflicted may show an increased cancer risk. This is the first reported case of a father and son with both Peutz-Jeghers Syndrome and colonic carcinoma.

Effect of local and parenteral immunization on implantation of Actinomyces viscosus T6 in rats.

Groups of rats immunized in the vicinity of the major salivary glands or immunized intraperitoneally with Actinomyces viscosus T6 and their sham-immunized controls were infected with the homologous bacterium. Significantly higher levels of salivary and serum antibody were induced by intraperitoneal than by salivary gland immunization. There were also significant inverse correlations between the levels of salivary and serum antibody and the levels of implantation of A. viscosus T6. The level of implantation of A. viscosus T6 was significantly lower in the immunized animals than in the controls. However, antibody had limited capacity to inhibit the establishment of this bacterium.

Natural transmission of Streptococcus sobrinus in rats: saliva and serum antibody responses to colonization.

One hundred and twenty weanling rats fed diet NIH 2000 that were free of Streptococcus sobrinus and other mutans streptococci were employed in this study. Sixty rats were inoculated orally with S. sobrinus 6715. Each infected rat (donor) was paired and housed with an uninfected recipient. Saliva and serum samples were collected from 24 (12 donor and 12 recipient) rats at the baseline (day 0) and from groups of 12 recipients sacrificed on days 10, 24, 38, and 52, and the level of infection with S. sobrinus was monitored. Salivary immunoglobulin A (IgA) and IgG and serum IgM and IgG antibodies reactive with whole cells (WC), glucosyltransferase (GTF), and the serotype carbohydrate (g) of S. sobrinus were measured by an indirect enzyme-linked immunosorbent assay. Although the rats were free of S. sobrinus and other mutans streptococci at baseline, they exhibited salivary IgA and serum IgM antibodies reactive with S. sobrinus WC, GTF, and g and serum IgG antibodies reactive with WC and GTF. Infection of recipients with S. sobrinus did not induce salivary antibodies reactive with WC, GTF, or g. In contrast, increases in serum IgM and IgG antibodies reactive with WC and serum IgM antibodies reactive with g were observed.

T cell chronic lymphocytic leukemia: presence in bone marrow and peripheral blood of cells that suppress erythropoiesis in vitro.

The pathogenesis of the anemia associated with malignancy was investigated in a patient with T cell chronic lymphocytic leukemia. The plasma clot culture system was used as a measure in vitro of erythropoiesis. The patient's peripheral blood and marrow T lymphocytes obtained both before and after transfusion therapy suppressed erythroid colony formation by normal human bone marrow cells. Pretreatment of the patient's bone marrow T cells by antithymocyte globulin (ATG) and complement reversed this suppression. In addition, pretreatment of the patient's marrow cells with ATG and complement markedly augmented erythropoiesis in vitro. The expression of erythroid activity caused by the selective destruction of the suppressor T lymphocytes in the patient's bone marrow with ATG and the suppression of normal erythropoiesis by the patient's bone marrow and peripheral blood lymphocytes suggest that interaction between the malignant T cell and the erythropoietin-responsive stem cell is important in production of anemia in this patient.

Eosinophilic granulocytes as a possible source of vitamin B12-binding protein.

Leucocyte B12 and B12-binding capacity were measured by Simultrac radioassay in eosinophilic granulocytes, neutrophilic granulocytes and leucocytes obtained from patients with chronic granulocytic and lymphocytic leukaemia. It is shown that (a) eosinophils are a possible source of B12-binding protein similar to neutrophils and (b) granulocytes in myeloproliferative disorders and normal neutrophils have similar B12 and B12-binding capacity indicating that increased B12 and B12-binding capacity in myeloproliferative disorders arise from an increase in myeloid cell turnover.

Appearance of a nonfunctional isozyme of hepatic glycogen synthase in late gestation.

Glycogen levels, glycogen synthase activities, and glycogen synthase protein levels were determined in liver tissues obtained from 14- to 19-day-old fetal mice, newborn mice, and adult mice. The results of these experiments demonstrate a significant increase in the quantity of hepatic glycogen synthase beginning at Day 17 of gestation and reaching adult levels at birth. However, during the same time period, there is a dramatic decrease in total glycogen synthase activity suggesting that the accumulating glycogen synthase molecules are unable to transfer UDP-glucose to glycogen. These inversely coordinated changes in the quantity and activity of glycogen synthase are consistent with the suggestion that glycogen synthesis in the near-term fetal mouse is being maintained by preexisting enzyme, while accumulating enzyme molecules may represent a quiescent isozyme.

Effect of peroral immunization of humans with Streptococcus mutans on induction of salivary and serum antibodies and inhibition of experimental infection.

Naturally occurring antibodies reactive with Streptococcus mutans whole cells were assayed in whole saliva, parotid saliva, and blood samples collected from eight human volunteers. The levels and serotypes of indigenous S. mutans in plaque and whole saliva samples were also determined. After baseline sampling the teeth were cleaned and the subjects were inoculated with streptomycin-resistant S. mutans strains Ingbritt (serotype c) and OMZ65 (serotype g). The level of implantation and duration of colonization were determined in plaque and saliva, and antibodies reactive with these strains were monitored in saliva and serum. After the implanted bacteria were shed, the subjects wee immunized by the daily ingestion of an enteric-coated capsule containing 25 mg of Formalin-killed, freeze-dried OMZ65 cells for 3 days and inoculation was repeated. The levels of antibodies and of implantation and the duration of colonization were monitored as before. One month after the bacteria could no longer be detected, the immunization and inoculation cycle was repeated except that the subjects were immunized for 7 days. Five of the eight subjects were successfully colonized by strains Ingbritt and OMZ65. The remaining three did not become colonized with either strain. Strain OMZ65 implanted at a higher level than did strain Ingbritt. Oral immunization did not result in a detectable antibody response in saliva or serum to whole bacterial cells. However, after both the first and second immunizations there were marked reductions in the peak levels of infection and the duration of colonization of both OMZ65 and Ingbritt.

Specific and nonspecific immune factors in dental plaque fluid and saliva from young and old populations.

Separate samples of supragingival dental plaque overtly free of blood were centrifuged to obtain the free fluid phase (plaque fluid). Bound protein was eluted from the plaque bacteria and matrix by washing the plaque with a low-pH buffer. The plaque fluid, low pH eluate, and whole saliva were assayed for immunoglobulins A, G, and M, the third component of complement, lysozyme, lactoferrin, and lactoperoxidase. Concentrations of total protein and albumin were also determined. Antibody reactive with specific plaque bacteria was detected by indirect immunofluorescent microscopy. Specific and nonspecific immune proteins were present in plaque fluid from adult subjects at significantly greater concentrations than in their saliva, which suggests that these proteins are concentrated in dental plaque. The results indicate that both saliva and gingival exudate contribute to the immunological proteins found in the free fluid phase of dental plaque. The observation that immunoglobulin A antibody reactive with plaque bacteria could be detected in plaque fluid suggests that a wide variety of immunological reactions may occur in the dental plaque. These potential interactions between host, plaque bacteria, and their products could serve to influence the plaque flora and its ability to induce disease.

Immunochemical and functional studies of Actinomyces viscosus T14V type 1 fimbriae with monoclonal and polyclonal antibodies directed against the fimbrial subunit.

Each of five monoclonal antibodies (mAbs) prepared against the type 1 fimbriae of Actinomyces viscosus T14V reacted with a 54 kDa cloned protein previously identified as a fimbrial subunit. This purified protein completely inhibited the reaction of a specific anti-type-1-fimbria rabbit antibody with A. viscosus whole cells. Maximum values for the number of antibody molecules bound per bacterial cell ranged from 7 x 10(3) to 1.2 x 10(4) for the different 125I-labelled mAbs and was approximately 7 x 10(4) for 125I-labelled rabbit IgG or Fab against either type 1 fimbriae or the 54 kDa cloned protein. Although the different mAbs, either individually or as a mixture, failed to inhibit the type-1-fimbria-mediated adherence of A. viscosus T14V to saliva-treated hydroxyapatite, each rabbit antibody gave 50% inhibition of adherence when approximately 5 x 10(4) molecules of IgG were bound per cell. However, binding of each corresponding rabbit Fab had no significant effect on bacterial attachment unless much higher concentrations were used. These findings suggest that antibodies directed solely against the 54 kDa fimbrial subunit do not react with the putative receptor binding sites of A. viscosus T14V type 1 fimbriae. Instead, inhibition of attachment by the polyclonal antibodies may depend on an indirect effect of antibody binding that prevents the fimbria-receptor interaction.