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Biomedical subjects

K Anderson

Publications and source records attributed to K Anderson.

At least 379 records · Page 21Linked to original sources

Mucin histochemistry of cystitis glandularis and primary adenocarcinoma of the urinary bladder.

We describe the histochemical properties of mucin in three cases of cystitis glandularis affecting the urinary bladder. Of particular importance is the positive staining reaction that was obtained with the periodate borohydride/potassium hydroxide/PAS (PB/KOH/PAS) technique, indicating the presence of O-acetylated sialic acids. This reaction has been regarded as unique to the epithelial mucins in the normal terminal ileum and large intestine. Therefore, cystitis glandularis represents a true mucous metaplasia of large intestinal type. A case of primary adenovillous carcinoma of the bladder associated with cystitis glandularis also produced O-acetylated sialomucin, whereas a primary adenocarcinoma of urachal origin did not. The demonstration of O-acetylated sialic acid producing glandular epithelium in the bladder cannot be assumed to represent a metastasis from a colorectal cancer. The PB/KOH/PAS staining technique may provide a means of distinguishing between primary adenovillous and primary urachal carcinoma of the bladder.

Adenocarcinoma↗

Early precursors of site-specific cancers in college men and women.

Physical and social characteristics recorded at college physical examination and reported in subsequent questionnaires to alumni in 1962 or 1966 by 50,000 former students from Harvard University and the University of Pennsylvania were reviewed for their relationship to major site-specific cancer occurrence. The records of 1,359 subjects who died with a major site-specific cancer in a 16- to 50-year follow-up period and of 672 subjects who reported such a cancer by mail questionnaire in 1976 or 1977 were compared with those of 8,084 matched classmates who were known to be alive and free of cancer at the time subjects with cancer had died or had been diagnosed. Cigarette smoking, as reported both in student years and years as alumni, predicted increased risk for cancers of the respiratory tract, pancreas, and bladder. Student coffee consumption was associated with elevated risk for leukemia, but it was unrelated to cancers of the pancreas and bladder. Male students with a record of proteinuria at college physical examination experienced increased risk of kidney cancer, and those with a history of tonsillectomy experienced increased risk of prostate cancer. Students who at college entrance reported occasional vague abdominal pain were at elevated risk for pancreatic and colorectal cancers in later years. Increased body weight during college was associated with increased risks of kidney and bladder cancers, whereas for alumni this index was associated only with kidney cancer. Increased weight-for-height during college (but not in 1962 or 1966) predicted increased occurrence of female breast cancer. Jewish students experienced elevated risk for subsequent cancers of the female breast, colon, and combined colorectum. These and other findings are presented as clues deserving further exploration for any etiologic significance that they may hold for the cancer sites studied.

Body Weight↗

Adult acute lymphoblastic leukemia phenotypes defined by monoclonal antibodies.

Pretreatment peripheral blood and/or bone marrow blasts from 90 adults with acute lymphoblastic leukemia (ALL) were analyzed as part of a prospective treatment protocol study. Specimens were tested by immunofluorescence cytofluorometry for reactivity with the following monoclonal antibodies (MoAbs): BA-1 (B cell antigen); T101, OKT11 (pan-T cell antigens [T]); 3A1 (T cell antigen); MCS-2 (myeloid antigen); J5 common ALL antigen (CALLA); BA4 (Ia antigen [Ia]); BA-2 (lymphohematopoietic antigen). Four major phenotypic groups were identified: B lineage ALL (BA-1+T-) (64%), T lineage ALL (T+BA-1-MCS-2-) (13%), unclassified ALL (BA-1-MCS-2-CALLA-T-) (9%) and myeloid antigen ALL (MCS-2+CALLA-T-) (7%). An additional group of patients, miscellaneous ALL (7%), was comprised of cases with unusual marker profiles. In B lineage ALL, all cases tested were Ia+MCS-2-, and the vast majority were CALLA+ (84%). In T lineage ALL, 42% expressed CALLA or Ia positivity. In unclassified ALL, the predominant phenotype was Ia+BA-2+. In myeloid antigen ALL, two of four tested were 3A1+ and all cases evaluated were BA-1-. Patients with myeloid antigen ALL were older (median age, 66 years) than patients in the other groups. The T lineage ALL group had higher leukocyte counts (median WBCs, 183,000/microL) and an increased incidence of anterior mediastinal mass at presentation. All patients received identical induction therapy. In CALLA+B lineage ALL, 30 of 46 (65%) achieved a complete remission. While the number of patients evaluated was small, 9 of 9 CALLA-B-lineage ALL and only two of six myeloid antigen ALL cases responded with a complete remission. The data suggest that these MoAbs are useful in the characterization of adult ALL.

Adult↗

Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer.

The majority of patients with advanced prostatic cancer respond either to castration or estrogen therapy. In an attempt to identify an alternative hormonal therapy, 25 symptomatic stage D prostate cancer patients were treated with megestrol acetate as initial hormonal therapy. Thirty-three patients were evaluable for response as defined by the National Prostatic Cancer Project criteria. Partial remission was observed in 11 patients and stable disease in 5, with an overall response rate of 70%. The projected median duration of response and survival were 10 and 20 months, respectively. Weight gain was common, but only two patients showed evidence of fluid retention. Gynecomastia, thromboembolic episodes, and gastrointestinal side effects were not observed in this group of patients, though two patients had increased pain shortly after therapy was initiated. Thus, in advanced prostatic cancer, megestrol acetate is effective primary therapy with minimal side effects.

Aged↗

Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels.

Estrogen (ER) and progesterone receptor (PR) levels in human breast cancer have been shown to have value in predicting response to a variety of hormonal therapies. However, the relationships between steroid receptor levels and tumor response and survival in patients treated with progestational agents for primary hormonal therapy have not been clearly defined. Forty-three advanced breast cancer patients, whose tumors had been assayed for ER and PR were treated with megestrol acetate as initial hormonal therapy. Twenty-five patients had ER and PR levels greater than 10 femtomole/mg cytosol protein, and the median ER and PR levels for the entire group were 114 fmol/mg and 100 fmol/mg, respectively. The overall response rate (complete and partial) was 46%, with a median duration of response of 66 weeks. Seventy percent of patients whose ER and PR were greater than 10 fmol/mg responded: Step-wise discriminant analysis showed that ER and PR were significantly related to response and that PR was the best predictor of response (P = .0034). Similarly, both ER and PR were significantly related to survival (P = .0001 for PR and P = .021 for ER). These data indicate that megestrol acetate is effective primary hormonal therapy in advanced breast cancer patients, and that ER and PR levels were significantly related to response and to survival duration. PR proved to be the best predictor of response in this group of patients.

Aged↗

Computer-implemented nutrition support of phenylketonuria.

This project demonstrates that computers can fill diet prescriptions for nutrition support but only if nutritionists who know how to fill diet prescriptions do the programming. The computer can provide information that is required to improve nutrition support, as well as save time that the dietitian can use in patient education. The computer, however, cannot replace the dietitian. It merely performs mathematical calculations. Establishment of the diet prescription, choice of products, and the use of the final formula and foods require trained judgment used in conjunction with appropriate clinical and laboratory data.

Dietetics↗

Effect of a sulfonium analog of dopamine on the depolarization-induced release of [3H]acetylcholine from mouse striatal slices.

P3 have synthesized a chemical analog or dopamine in which the amino group has been replaced by a charged dimethylsulfonium group. The dopaminergic activity of this drug was evaluated by determining its ability to inhibit the depolarization-evoked release of [3H]acetylcholine from mouse striatal slices. The slices were preincubated with [3H]choline (0.1 microM) and then superfused in physiological medium. [3H]Acetylcholine release was induced by exposure of the slices to a high potassium medium (12.5 mM) for 5 min. The sulfonium analog of dopamine, dopamine, and apomorphine inhibited the evoked [3H]acetylcholine release with IC50 values of approximately 10, 2.0, and 0.3 microM respectively. The inhibition by the sulfonium analog was reversed by fluphenazine (1 microM), suggesting that the inhibition of [3H]acetylcholine release was due to the activation of dopaminergic receptors. The sulfonium analog also inhibited the uptake of [3H]dopamine into striatal slices and caused the release of exogenously taken up [3H]dopamine from these slices. The release of [3H]dopamine by the sulfonium analog was inhibited by cocaine (3 microM), suggesting that the drug-induced release of [3H]dopamine was dependent on the carrier-mediated uptake of the sulfonium analog into dopaminergic neurons. The inhibition of the evoked [3H]acetylcholine release by high concentrations (30 and 60 microM) of the sulfonium analog did not appear to be mediated by endogenous dopamine release, since the analog still inhibited [3H]acetylcholine release from slices after reserpine-alpha-methyl-p-tyrosine treatment. However, the inhibitory effect of the sulfonium analog at 10 microM was reduced by reserpine-alpha-methyl-p-tyrosine treatment, suggesting that the inhibition at lower concentrations was mediated through endogenous DA release. These results suggest that a charged compound can act as a substrate for the dopamine carrier and can activate the dopamine receptor regulating acetylcholine release. They also indicate that the nitrogen on the dopamine molecule is not essential for dopamine agonist activity.

Acetylcholine↗

Metastatic carcinoma with an unknown primary.

The patient is a 54-year-old white female who was well until 3 weeks prior to admission when she noted vague right upper quadrant pain exacerbated by meals. She lost 12 lbs over that period of time. She complained as well of posterior scalp, left hip, and back pain on initial presentation. Physical examination at the time of admission to hospital showed a middle-aged female in no acute distress. Her vital signs were normal. There was a 1.5 X 1.5-cm firm, tender nodule over the occiput. There was no peripheral adenopathy. The breasts, lungs, and heart were normal. The liver was 14 cm in span. The remainder of the physical examination including a pelvic examination was unremarkable. On admission, the only abnormal laboratory studies were SGOT 106, SGPT 139, and alkaline phosphatase 190. Her chest X ray, flat plate of the abdomen, and mammograms were all normal.

Adenocarcinoma↗

Biological and macromolecular properties of murine cells persistently infected with MHV-JHM.

A persistently-infected neuroblastoma culture [Neuro-2A( JHMV )] was established with the murine hepatitis virus JHM [MHV-JHM]. After 100 days of passage, the endogenous virus [Neuro-2A( JHMV ) end] released by this culture was unable to induce the syncytia typical of MHV-JHM and the endogenous virus was not temperature-sensitive. The Neuro-2A( JHMV ) culture was cured of virus production by passage under neutralizing antibody [Neuro-2A( JHMV )Ab]. The Neuro-2A( JHMV ) and the Neuro-2A ( JHMV ) Ab cultures were as susceptible to heterologous infection with mengovirus and vesicular stomatitis virus as the uninfected Neuro-2A culture. However, the Neuro-2A ( JHMV ) and Neuro-2A( JHMV ) Ab cultures were partially resistant to homologous superinfection by MHV-JHM and the closely related MHV-A59. Virus related to MHV-JHM was rescued from the antibody-cured cells by cell fusion. The synthesis of MHV-JHM specific antigens by Neuro-2A( JHMV ) cells, Neuro-2A( JHMV ) Ab cells and 17 Cl-1 cells infected by Neuro-2A( JHMV ) end was studied by SDS-PAGE. The genomic RNAs of MHV-JHM and Neuro-2A( JHMV ) end were compared by oligonucleotide mapping. The results of the protein and RNA studies indicated that the genome of Neuro-2A( JHMV ) end was substantially modified from the genome of MHV-JHM, but the modifications did not significantly alter the molecular size of the viral-specific proteins.

Animals↗

Protein synthesis in cells infected by murine hepatitis viruses JHM and A59: tryptic peptide analysis.

The structural and intracellular proteins of the murine hepatitis viruses MHV-JHM and MHV-A59 were studied by tryptic peptide mapping. The results demonstrated that the virions contained three distinct proteins: the two related chains of the E2 complex, the nucleocapsid protein and the heterogeneous E1 complex. Five distinct virus-specific proteins were synthesized by infected cells. Three of the five intracellular proteins contained tryptic-peptides with properties similar to the three structural proteins. Models describing the evolution of the proteins are proposed. Although the pathogenic properties of MHV-JHM and MHV-A59 differ greatly, the tryptic peptide maps of the corresponding proteins of these MHV strains were remarkably similar.

Electrophoresis, Polyacrylamide Gel↗

The use of penile tumescence measures with incarcerated rapists: further validity issues.

The use of penile tumescence to categorize and assess the treatment of sex offenders has gained increasing popularity. Recent publications have expanded the use of tumescence measures for the classification of rapists. The majority of studies in the past using mainly subjects seeking treatment or admitting to difficulties in controlling rape urges have shown the technology to be a valuable asset in classification. The present investigation, however, points out the limitations of using this technology in certain populations. The responses of incarcerated rapists and incarcerated nonrape offenders were compared. Analysis of the data indicated that there were no significant differences between the responses of rapists and nonrapists and that the rape index proposed by Abel et al. (1978) did not reliably classify incarcerated rapists. This paper points out the limitations of penile tumescence assessment with certain populations and discusses possible reasons for the failure to discriminate in this investigation.

Adult↗

Early precursors of urogenital cancers in former college men.

Physical and social characteristics recorded at college physical examination or reported at subsequent alumni questionnaire in 1962 or 1966 by 47,271 male former students from Harvard University and the University of Pennsylvania were reviewed for their relationship to risk for cancers of the kidney, bladder, prostate and testis. The records of 213 subjects who died with 1 of these cancers in a 16-50 year followup period and of 280 subjects who reported such a cancer by mail questionnaire in 1976 or 1977 were compared with those of 1,972 matched classmates who were known to be alive and cancer-free at the time subjects with cancer had died or were diagnosed. Students with a record of proteinuria at college physical examination experienced increased risk of kidney cancer. Higher levels of body weight during college were associated with elevated risks of kidney and bladder cancers; however, increased weight in 1962/1966 related only to kidney cancer. A history of cigarette smoking as reported by questionnaire in 1962/1966 predicted increased occurrence of bladder cancer. Students with a history of tonsillectomy at college entrance experienced increased risk of prostate cancer, and those who reported cancer history in 1 or both parents were at increased risk for testicular cancer. These and other findings are presented as clues deserving further exploration for any etiological significance they may hold for the cancer sites studied.

Aged↗

Differential effects of mecamylamine on the nicotine induced changes in amine levels and turnover in hypothalamic dopamine and noradrenaline nerve terminal systems and in the secretion of adenohypophyseal hormones in the castrated female rat. Evidence for involvement of cholinergic nicotine-like receptors.

The effects of mecamylamine on the nicotine induced changes in hypothalamic catecholamine (CA) levels and turnover in female rats ovariectomized for one month have been evaluated using a quantitative microfluorimetric approach to measure CA levels in sections of brains treated according to the Falck-Hillarp procedure for the cellular demonstration of CA. In the same group of animals the serum prolactin, LH, FSH, TSH, GH and corticosterone levels were measured using radioimmunoassay procedures. The nicotine treatment induced a significant depletion of amine stores and an increase of amine turnover in dopamine (DA) and noradrenaline (NA) nerve terminals of the median eminence and of the peri- and paraventricular and dorsomedial NA systems of the hypothalamus using the tyrosine hydroxylase (TH) inhibition model. Mecamylamine (2 X 1 mg/kg) partly counteracted the nicotine induced reduction of amine stores in peri- (anterior part) and paraventricular NA nerve terminal systems as well as the nicotine induced increase of NA turnover in these systems, but not the action of nicotine on the CA systems of the median eminence. Nicotine (4 X 2 mg/kg) significantly and markedly reduced prolactin, LH, TSH, and GH secretion increased corticosterone secretin but did not influence FSH secretion. These effects were partly counteracted by mecamylamine (2 X 1 mg/kg) in the case of prolactin, LH and TSH secretion but not in the case of GH and corticosterone secretion. Taken together the results show that mecamylamine treatment (2 X 1 mg/kg) differentially counteract nicotine induced changes of amine levels and turnover in peri- (anterior part) and paraventricular NA nerve terminal systems indicating that the cholinergic nicotine-like receptors located in peri- (anterior part) and paraventricular areas may be more susceptible to the blocking activity of mecamylamine than those located in the median eminence area. Furthermore, the inhibitory effects of nicotine on prolactin, LH and TSH secretion are differentially counteracted by mecamylamine. In conclusion, other inhibitory systems than the tuberoinfundibular DA neurons in the MPZ and LPZ must also be involved in mediating the inhibitory effects of nicotine on prolactin, LH and TSH secretion and different types of cholinergic nicotine-like receptors may exist.

Animals↗

Predictors of drug-resistant Mycobacterium tuberculosis.

Drug susceptibility testing is usually performed when Mycobacterium tuberculosis organisms are recovered from Asian immigrants or from patients whose sputum remains culture positive despite several months of antituberculosis medication. Alcoholism, previous antituberculosis treatment, history of adverse reactions to previous treatment, and patient unreliability have also been suggested as risk factors, but the ability of these factors to predict the presence of drug-resistant organisms has not been assessed. Starting in January 1980, the Washington State Tuberculosis Laboratory began testing every positive M. tuberculosis culture for drug resistance. This enabled us to prospectively evaluate the sensitivity and specificity of 7 risk factors for drug resistance in consecutive patients. From January 1, 1980, through December 31, 1982, cultures from 803 patients were positive for M. tuberculosis; 766 of these (95%) were tested for drug resistance. The incidence of resistance was 13% (101/766). Of the 101 patients with drug-resistant organisms, 61 (60%) were Asian, supporting the need to routinely test Asian immigrants for drug-resistant disease. The ability of the other risk factors to separate the 40 non-Asians (40%) with drug-resistant disease from the group of 513 non-Asians with drug-sensitive organisms was poor. All risk factors were insensitive and had a high false positive rate. These results demonstrate that the presence of drug-resistant disease in non-Asians cannot accurately be predicted. This finding suggests that all cultures of M. tuberculosis should be tested for drug sensitivity, and that in areas where the incidence of drug resistance is sufficiently high, initial treatment should be with 3 drugs until drug susceptibility is known.

Antitubercular Agents↗

Radioprotection of normal tissues against gamma rays and cyclotron neutrons with WR-2721: LD50 studies and 35S-WR-2721 biodistribution.

The ability of WR-2721 to protect mice against two modes of death following whole-body radiation with 137Cs gamma rays or d(22)+Be neutrons was examined. For single fractions, 400 mg/kg WR-2721 was administered prior to irradiation. In two-fraction exposures, the dose was 275 mg/kg given prior to each fraction. Dose modification factors (DMFs) were calculated as ratios of LD50 values. For single fractions of gamma rays, the DMF was 1.74 for the LD50/7 end point and for LD50/30, the DMF for single fractions was 2.25. For two fractions 3 hr apart, it was 1.88. For single fractions of cyclotron neutrons, the DMF was 1.32 for LD50/7. Measured with the LD50/30 end point, the DMF for single neutron doses was 1.41 and for two fractions, 1.19. Substantial radioprotection of bone marrow and intestinal epithelium against cyclotron neutrons was seen in these investigations. Biodistribution studies were done following ip injection of 35S-labeled WR-2721 into C3H mice bearing RIF-1 tumors. Blood levels peaked at 10 min after injection and declined thereafter. Most normal tissues achieved maximum levels of 35S at 30 to 60 min postinjection and high concentrations were retained in most tissues for up to 2 hr. Assuming that all 35S is in parent compound or dephosphorylated radioprotective metabolites, the concentration of protector (milligram per gram tissue) in various organs at 30 min postinjection ranked as follows: kidney greater than submandibular gland much greater than liver = lung greater than gut greater than heart much greater than blood greater than skin greater than tumor greater than brain. High levels of 35S were achieved and retention times were long in certain normal tissues which respond at early or late times postradiation and may be dose limiting in radiotherapy: kidney, liver, salivary gland, and lung. These combined observations suggest that there is potential for protecting dose-limiting, late-responding normal tissue in the radiotherapy of human cancer with both neutrons and conventional radiotherapy.

Amifostine↗

Early precursors of pancreatic cancer in college men.

From college data on 50,000 male former students, the records of 126 men who died of pancreatic cancer in a 16-50 yr follow-up period were compared with those of 504 surviving classmates with respect to physical and social characteristics. Return mail questionnaires received from 30,000 surviving alumni in 1962 or 1966 also were reviewed for characteristics that might predict altered risk of pancreatic cancer. Strong positive associations were found for cigarette smoking as reported both during college (p less than 0.001) and at time of questionnaire return (p = 0.03). Smoking 10 or more cigarettes per day during college corresponded to a relative risk of 2.6 with 95% confidence limits 1.5 to 4.6, and a positive smoking history at questionnaire return yielded a relative risk of 2.4 (1.1-5.1). No association was found for collegiate coffee drinking, either before or after adjustment for cigarette smoking. The relative risk for coffee drinking adjusted for smoking was 1.1 (0.7-1.8). In contrast, collegiate tea consumption was associated with a reduction in pancreatic cancer risk. The relative risk for tea drinking adjusted for smoking was 0.5 (0.3-0.9). Men who at college physical examination complained of occasional abdominal pain or discomfort had increased relative risk of pancreatic cancer (3.1 : 1.1-9.0) in the follow-up period.

Adolescent↗