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Biomedical subjects

K M Anderson

Publications and source records attributed to K M Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1986

Active tuberculosis after isoniazid chemoprophylaxis of Southeast Asian refugees.

The outcome of isoniazid chemoprophylaxis for tuberculosis was assessed in refugees from Southeast Asia. From July 1979 through June 1982, 2,795 tuberculin-positive refugees were prescribed isoniazid chemoprophylaxis at the time of their resettlement in King County, Washington. Through December 1983, 19 cases of active tuberculosis had arisen in those refugees. The annual incidence varied between 2.04 and 2.86 cases per 1,000 receiving treatment during the 4 yr after initiation of chemoprophylaxis (cumulative incidence, 9.66 per 1,000). Seven of the cases of tuberculosis occurring after isoniazid chemoprophylaxis were pulmonary, 1 was pulmonary and extrapulmonary (lymphatic), and 11 were extrapulmonary alone (lymphatic, 6 cases; pleural, 4 cases; soft tissue, 1 case). Fifteen of the 19 cases were culture positive, among which 8 M. tuberculosis isolates were susceptible to isoniazid and 7 were resistant. A case-control analysis showed that poor compliance, defined as taking isoniazid for 3 months or less, was associated with a sixfold increase in risk for subsequent isoniazid-susceptible tuberculosis but with no increased risk for subsequent isoniazid-resistant disease. Thus, active tuberculosis continued to occur with a low but relatively constant incidence after prescription of isoniazid chemoprophylaxis to Southeast Asian refugees. In this setting, poor compliance with chemoprophylaxis predisposed to isoniazid-susceptible, but not to isoniazid-resistant tuberculosis. There is a need to improve the approach to prevention of tuberculosis in Southeast Asian refugees.

Adolescent↗
PubMed1986

Tuberculosis screening in Washington state male correctional facilities.

The four major penal institutions for men in Washington state were surveyed in June 1983, to assess the quality of tuberculosis screening and the proportion of residents who were reactors. A total of 4,744 medical charts of current residents were reviewed of which 4,269 (90.0 percent) had skin test results recorded. The proportion of inmates residing in the four institutions during 1983 who were reactors was 12.5 percent. To describe the demographic characteristics and health status of reactors and nonreactors more fully, a detailed data abstraction was performed for those inmates newly admitted during 1982. The proportion of this subgroup of 1,176 men entering the prison system during 1982 who were reactors was 14.2 percent. There was no evidence of tuberculosis transmission within the institutions. Three converters were recognized. However, all three conversions were identified upon reentry of inmates following periods of release. This study supports an earlier recommendation for skin testing upon entry or reentry for residents, and only upon initial hiring of employees. The Washington State Department of Corrections was advised to continue skin testing upon entry or reentry for residents and only upon initial employment of personnel.

Adolescent↗
PubMed1986

Rat ventral prostate cell lysis at 2 degrees C.

In order to physically separate epithelial from nonepithelial cells, well-minced rat ventral prostate at 2 degrees C was passed through a tissue sieve, and the disrupted tissue suspended and washed several times before centrifugation on a Ficoll gradient. While limited separation of single prostate epithelial and nonepithelial cells and small aggregates could be achieved, the yield of intact undamaged cells was low, and many nuclei contaminated the 2 major cell fractions obtained from the gradient. During subsequent experiments, it became apparent that most single cells released from prostates minced at 2 degrees C rapidly lysed, yielding cytoplasmic debris and cell nuclei. Yet the morphology of red and white blood cells, examined by light microscopy, was unaffected, suggesting a soluble factor was not responsible. These results indicated that mechanical dissociation of rat ventral prostate at 2 degrees C with release of single cells was accompanied by a powerful prostate cell-associated lytic 'event', affecting both epithelial and connective tissue cells, without destruction of cell nuclei or accompanying red and white blood cells. Some properties of this process are described in this report.

Animals↗
PubMed1986

Megestrol acetate: first-line therapy for advanced breast cancer.

Megestrol acetate as initial hormonal therapy produced a 40% objective response rate in 53 patients with advanced breast cancer; another 26% achieved stable disease. For 19 patients with visceral-dominant disease, the response rate was 42%. To investigate the effect of the order of sequential hormonal therapy, records of 66 patients treated with tamoxifen before megestrol acetate or with megestrol acetate before tamoxifen were reviewed retrospectively. Of the 24 patients who were given megestrol acetate first, nine (38%) had objective response to primary therapy, and four (17%) to secondary therapy. Among the 42 patients treated with tamoxifen first, there were nine (21%) objective responses to primary therapy and eight (19%) responses to secondary therapy. Results show that megestrol acetate is effective first-line hormonal therapy for advanced breast cancer. Megestrol acetate can be used as primary hormonal therapy and tamoxifen as secondary hormonal therapy, as an alternative to the more usual reverse order. One may also consider megestrol acetate for some advanced breast cancer patients with visceral-dominant disease.

Antineoplastic Agents↗
PubMed1985

Identification of prostate and other cancers by two-dimensional protein electrophoresis.

Some cancers are so undifferentiated as to preclude their identification, and this hinders selection of an appropriate therapy. The systematic analysis and cataloguing of electrophoresed proteins from identified cancers and their comparison with the protein patterns from histologically indeterminate cancers should provide a general means of identifying the latter.

Adenocarcinoma↗
PubMed1985

Qualitative analysis of Coomassie-blue-stained proteins from normal prostate, benign prostatic hypertrophy, or adenocarcinoma of the prostate, separated by two-dimensional protein electrophoresis.

Samples from nine normal prostates (N), ten benign hypertrophic prostates (BPH), and eight adenocarcinomas of the prostate (ACP), obtained from the National Prostatic Cancer Project were analyzed by two-dimensional (2D)-protein electrophoresis. Qualitative analysis of Coomassie-blue-stained acidic proteins between pI 3.5 and 6.8 yielded these results: The total number of enumerated proteins was 136 (N), 107 (BPH), and 147 (ACP). Ninety-two denoted proteins were deemed common to the three kinds of samples, three were considered present in N and BPH, 7 in BPH and ACP, and 28 in N and ACP. Thirteen, five, and 20 proteins were detected only in N, BPH, or ACP. These proteins cannot be considered "unique" to their respective samples, since amounts of protein that do not exceed the minimum sensitivity of the dye may be present in the other samples. The similarity in the patterns of proteins from these three types of prostate samples is consistent with the following hypothesis: The distribution of proteins from histologically ambiguous prostate samples will correlate more closely with these protein profiles than with those associated with cancers originating from other organs.

Adenocarcinoma↗
PubMed1985

Parathyroid adenomas evaluated by Tl-201/Tc-99m pertechnetate subtraction scintigraphy and high-resolution ultrasonography.

Thallium-201/technetium-99m pertechnetate subtraction scintigraphy of the parathyroid glands was performed in a prospective study of 33 patients who had undergone bilateral neck exploration for elevated serum calcium and serum parathyroid hormone levels. In 31 cases, the Tl-201/Tc-99m subtraction technique yielded an overall sensitivity of 81%, specificity of 99%, and accuracy of 94% for identifying solitary parathyroid adenomas. Tl-201/Tc-99m subtraction scintigraphy correctly identified 73% of parathyroid adenomas weighing less than 499 mg, 79% of those weighing 500-1,499 mg, and 100% of adenomas weighing more than 1,500 mg. In a subgroup of 24 patients with solitary parathyroid adenomas who underwent both scintigraphy and high-resolution sonography, the sensitivity, specificity, and accuracy of both procedures were similar.

Adenoma↗
PubMed1985

Metastatic breast cancer from an occult primary provisionally identified by steroid receptor content and two-dimensional protein electrophoresis: some problems associated with the use of the latter technique.

Occult primary breast cancer in a patient presenting with undifferentiated metastatic adenocarcinoma in an inguinal lymph node was provisionally diagnosed by the steroid receptor content of its metastases and by the sclerotic pattern of osseous metastases. This diagnosis was supported by the presence of several proteins electrophoresed in 2 dimensions that may be common to other identified adenocarcinomas of the breast. These proteins appear to be absent from a representative adenocarcinoma of the ovary and of the uterus, at least at the level of sensitivity provided by the dye used to detect them. Some clinical implications for the use of two-dimensional protein electrophoresis in identifying undifferentiated cancers are considered.

Bone Marrow↗
PubMed1984

Nuclear protein synthesis in a temperature-sensitive Chinese hamster ovary cell line at 40 degrees C.

We examined the incorporation of radioactive amino acids into nuclear proteins occurring at nonpermissive conditions in tsH1 Chinese hamster ovary cells with a temperature-sensitive defect in cytosol nonmitochondrial protein synthesis. In leucine-free medium at 40 degrees C, total cellular protein synthesis declined by 1-1.5%/min. As reported by others, preincubating these cells at 42 degrees C for 5-10 min sharply increased the rate of decline. The synthesis of acidic nuclear proteins at nonpermissive conditions (40 degrees C + 300 micrograms/ml cycloheximide) was demonstrated by the nuclear incorporation of 3H-tryptophan. Radioactivity, seen by autoradiography to be associated with these isolated Triton-X-100-washed nuclei, was released after incubating labelled nuclei with proteolytic enzymes. During incubation of tsH1 cells at nonpermissive conditions, pulse/chase experiments were consistent with the loss of some nuclear radioactivity into the cytoplasm. The distribution of cytosol and nuclear proteins, labelled at permissive or nonpermissive conditions and separated by isoelectric focusing, differed quantitatively and probably qualitatively, confirming the residual synthesis of acidic nuclear proteins at 40 degrees C in the presence of cycloheximide. Most newly synthesized acidic proteins retained by nuclei from cells labeled at nonpermissive conditions were present in a transciptionally active chromatin fraction. Although under these conditions the apparent rate of cellular RNA synthesis was unchanged, inhibiting residual cycloheximide-resistant nuclear protein synthesis with puromycin proportionately reduced RNA synthesis. Preincubating cells with 20 micrograms/ml of actinomycin D did not inhibit residual labelling of nuclear proteins; effects on residual nuclear labelling of impaired mitochondrial respiration were ambiguous. Nuclear proteins labelled under nonpermissive conditions probably included some of the 'prompt' heat shock proteins recently described. Provided certain assumptions are correct, our results are consistent with very limited protein synthesis associated with and even intrinsic to cell nuclei. They also suggest that this residual cycloheximide-resistant protein synthesis could be concerned with optimum synthesis or processing of certain nuclear RNA species.

Animals↗
PubMed1983

The distribution of acidic coomassie blue-stained proteins from uninvolved human liver, hepatoma, normal colon, primary colon cancer, and colon metastases to the liver, determined by two-dimensional protein electrophoresis.

The distribution of Coomassie blue-stained proteins from uninvolved regions of 4 human livers, from 1 hepatocellular carcinoma, and from 4 samples each of uninvolved colon, primary adenocarcinoma of the colon, and colon cancer metastatic to the liver was analyzed by two-dimensional protein electrophoresis. From a comparison of acidic proteins between pI 3.5 and 6.5, we conclude (1) that the majority (66 of 82) of denoted acidic proteins from 4 normal liver samples were represented in the hepatocellular carcinoma. Fifty-one of 58 proteins denoted in the 4 colon samples were detected in each of the 4 primary colon cancers; (2) that the "normograms" of proteins from normal colon and normal liver differed in many details, and their dissimilar patterns identified the source of the sample; (3) that hepatoma and primary adenocarcinoma of the colon were easily distinguished by their distribution of proteins; (4) that colon cancer metastatic to the liver contained a majority (50/58) of acidic proteins enumerated in primary colon cancer. These results indicate that uninvolved liver and colon and their primary or secondary cancers can be identified by their distribution of electrophoresed acidic proteins.

Adenocarcinoma↗
PubMed1983

Provisional "normograms" for identifying adenocarcinomas of the prostate or colon and hepatocellular carcinoma derived from their distribution of proteins separated by two-dimensional electrophoresis.

The distribution of proteins in samples from 8 prostate and 4 colon adenocarcinomas and 1 hepatoma was analyzed by 2-dimensional protein electrophoresis. Composite "normograms" based upon their distribution of proteins were developed from these patterns. Particular attention was paid to acidic proteins between pI 3.5 and 5.9. Of 161 proteins enumerated, 23 of the first 135 were present in prostate cancers, compared with 68 in colon cancer and 85 in the hepatoma. The 26 proteins denoted from nos. 135 to 161 were prostate associated, and none was evident in the colon or hepatoma samples. Twenty-seven prostate, 20 colon, and 48 liver cancer proteins were "unique" to each of the 3 cancers, respectively. The patterns of protein associated with each type of cancer were so dissimilar that with this technique no difficulty should be experienced in distinguishing these carcinomas originating from 3 different types of "stem" cells without obligatory recourse to microscopy.

Adenocarcinoma↗
PubMed1983

Effects of castration and replacement of androgen on the separation of rat ventral prostate cells by Ficoll gradient centrifugation.

When regressing or growing (hypertrophic) cells from collagenase-digested ventral prostates were centrifuged on isokinetic Ficoll gradients for 6-8 min, they distributed into four fractions. Because of changes in epithelial cell morphology and density following castration to induce regression and replacement of androgens to cause cell growth, and contrary to results with normal rat ventral prostate, stromal cell fraction 2 was contaminated to a greater extent with regressing epithelial cells, as judged by their morphology and binding of radioactive androgens. However, centrifugation for 3 min increased the purity of epithelial cell fraction 4, although the yield of desired cells was reduced. Most cells from endocrine-manipulated rats were viable, as judged by exclusion of trypan blue and the initial incorporation of 3H-uridine. Cells centrifuged on a similar gradient of Percoll separated by a 'sieving' effect, which inverted the order of cellular fractions and removed red blood cells from fraction 2. Metrizamide offered no advantages, compared with Ficoll or Percoll. Neither physiologic nor pharmacologic amounts of testosterone returned the morphology of isolated epithelial cells to normal. To obtain consistent results with prostates from normal or hormone-manipulated rats, one should take care to select an active preparation of collagenase, avoid the use of very old animals, cool the tissue after it is dissociated, and do not apply undigested clumps of cells or overload the gradient. If attention is paid to these details, populations enriched in viable regressing or growing prostate epithelial or stromal cells can be obtained from hormonally manipulated rats.

Androgens↗
PubMed1982

Mithramycin impairs the release of 45Ca from bone induced by prostaglandin E2 or multiple myeloma sera. Implications for a novel means of local tumor control.

Some tumors release factors able to activate host osteoclasts. Mithramycin at sub-tumoricidal doses inhibits the release of calcium mediated by osteoclasts. If invasion of bone by a cancer requires activation of these cells, their intermittent "blockade' might impede the development of metastases to bone or their local extension. Fetal rat bones prelabelled with 45Ca were cultured in the presence of 10(-7) M prostaglandin E2, sera from normal individuals, or from patients with multiple myeloma. Additional samples preincubated for 3 h with 1 microgram/ml of mithramycin, were washed before culture. Compared with controls, prostaglandin E2 stimulated the release of 45Ca by 28% (5 experiments) and mithramycin inhibited release by 15% (3 experiments). Preexposure to this cytotoxic antibiotic before culture with PGE2 reduced the augmented release. Sera from 4 patients with multiple myeloma were incubated with 45Ca-labelled bones, some pretreated with mithramycin. An additional 29% release of 45Ca (4 experiments) was prevented by mithramycin. These results are consistent with the hypothesis that augmented release of 45Ca due to stimulatory factors such as prostagladins or factors in sera from patients with multiple myeloma can be partially inhibited by pretreatment with mithramycin. Possibly, intermittent blockade of host osteoclasts can impair formation of metastases to bone by cancers dependent upon their activation for this event, or reduce the extent of local invasion by established metastases. Modifying the behavior of a cancer by altering the host-response to factors which it releases represents a potential alternative to cytotoxic chemotherapy.

Animals↗
PubMed1981

Two-dimensional protein electrophoresis and the identification of histologically indeterminate human cancers.

It is proposed to identify histologically indeterminate human cancers by comparing their qualitative content of stained proteins, separated by two-dimensional electrophoresis, with patterns of proteins from a series of identified human cancers of comparable or different stem cell origin. The hypothesis to be tested is that in cancer, biochemical ontogeny, reflected in the distribution of cellular and tissue proteins, will recapitulate phylogeny, albeit in a manner less organized than normal. Patterns of protein from cancer cells, whether histologically identified or not but originating from embryologically similar stem cells, are expected to exhibit greater homology, compared with protein profiles of cancer cells derived from stem cells of different embryologic origin. Normal or cancer cell proteins common or unique to one or more cell sources can be identified, and subsets of proteins that characterize cancer cells of specific stem cell origin identified. There are reasons to believe that cancer cells rarely, if ever express properties inconsistent with the basic cellular commitment of their stem cell of origin. Photo-optical scanning and computer-assisted analysis will greatly facilitate collating the many hundreds of discrete proteins, among which those used to characterize different cancer cells are to be found.

Electrophoresis, Polyacrylamide Gel↗