Radio-chemotherapy for invasive carcinoma of the bladder.
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Biomedical subjects
Publications and source records attributed to P Griffin.
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The purposes of this participatory research project were to describe the experiences of thirteen lesbian and gay educators and to empower the participants through collective reflection and action. Each participant was interviewed and given a copy of her or his audio-tape and transcript. Using these materials, each participant developed a profile of themselves to share with the other participants. During a series of group meetings that spanned fifteen months, participants discussed their experiences, searched for common themes, and planned two collective actions. This chapter describes the professional experiences of these lesbian and gay educators and the process of empowerment that changed their lives.
This report describes the physical, chemical, and biological characterization of recombinant human relaxin (rhRlx) used as a probe to establish the disulfide pairing in native human relaxin. This strategy is necessary since native human relaxin is only available in the nanogram range. The relaxin molecule is composed of two nonidentical peptide chains, an A-chain 24 amino acids in length and a B-chain of 29 amino acids, linked by two disulfide bridges with an additional disulfide linkage in the A-chain. Native relaxin isolated from human corpora lutea was compared to rhRlx by reversed-phase chromatography, partial sequence analysis, mass spectroscopy, and bioassay. The potency of rhRlx was established by its ability to stimulate cAMP from primary human uterine endometrial cells. Native relaxin isolated from human corpora lutea was equipotent to chemically synthesized relaxin, which in turn was equipotent to rhRlx. A tryptic map was developed for rhRlx to confirm the complete amino acid sequence and assignment of the disulfide bonds. The three disulfide bonds (CysA10-CysA15, CysA11-CysB11, and CysA24-CysB23) were assigned by mass spectrometric analysis of the tryptic peptides and by comparison to chemically synthesized peptides disulfide linked in the two most probable configurations. In addition, the observed amino acid composition and sequence of rhRlx was in agreement with that predicted from the cDNA sequence with the exception that the A-chain amino terminal was pyroglutamic acid. The migration of rhRlx upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis was consistent with a monomeric structure, and the identity of the band was demonstrated by immunoblotting.
The role of pyroglyphid mites in house dust allergy is well established and the major allergens from the common house dust mites (Dermatophagoides species) have been characterized. There is, however, relatively little progress in the understanding of the human IgE response to non-pyroglyphid storage mites, allergenic crossreactivity with other mite species and extent of environmental exposure. We studied 196 individuals from an urban environment who were not occupationally exposed to storage mites and found a 24% prevalence of specific IgE antibody to Dermatophagoides pteronyssinus and a 14% prevalence of RAST positivity to at least one of three storage mites, Acarus siro, Lepidoglyphus destructor and Tyrophagus longior. All individuals with a positive RAST to storage mites had specific IgE to D. pteronyssinus. RAST inhibition studies with the eight sera with greater than 2% RAST binding to both families of mites showed considerable crossreactivity between D. pteronyssinus and the storage mites A. siro and T. longior and limited crossreactivity between D. pteronyssinus and L. destructor. This suggests that at least some of the response to storage mites observed by direct RAST is a consequence of crossreactivity with the more abundant D. pteronyssinus.
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We have explored the antigenic and allergenic relationship between the house dust mite Dermatophagoides pteronyssinus and three species of storage mite, Glycyphagus destructor, Acarus siro, and Tyrophagus longior. Crossed immunoelectrophoresis demonstrated that all the mite extracts contained multiple antigens but that there was only limited cross-reactivity between the different species. Six sera were obtained from workers exposed to storage mites and with occupationally related lower respiratory tract symptoms. All workers had specific IgE to D. pteronyssinus and to one or more of the storage mites. The pattern of reactivity varied between the different sera, two responded primarily to D. pteronyssinus and A. siro and four sera to D. pteronyssinus and G. destructor. Only weak responses were observed to T. longior. RAST-inhibition and affinity-absorption experiments demonstrated that D. pteronyssinus had at least three groups of distinct allergenic determinants, determinants specific to D. pteronyssinus, determinants shared with A. siro, and determinants shared with G. destructor. Similarly, both A. siro and G. destructor have specific allergenic determinants and determinants shared with D. pteronyssinus. The findings demonstrate the complexity of the immunologic responses to the different mite species.
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When injected into 12-day-old suckling rats, dexamethasone caused a precocious disappearance of Fc gamma receptors from enterocytes of the proximal small intestine. However, dexamethasone appeared to be necessary for the maintenance or production of such receptors in foetal rat gut cultured in vitro.
Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.
The time course of Fc gamma receptor expression on isolated enterocytes of the small intestine of rat fetuses and sucklings has been studied. This was achieved principally using indicator sheep red blood cells (SRBC) sensitized with rabbit IgG in an erythrocyte-antibody rosette assay which detects receptors located mainly on the lateral and basal plasma membrane, and in a more limited way using binding of rabbit IgG to metabolically inhibited gut as detected by immunofluorescence and which detects receptors located on the apical brush border. From the time they were first detectable in the rosette assay (20-day-old fetuses) to the time they disappeared (22-day-old sucklings) such receptors were found always to be acid pH dependent and restricted to enterocytes from the proximal region. Acid pH, Fc-dependent binding of rabbit IgG to metabolically inhibited gut was first detectable at 21 days gestation and there were indications that receptors differentiate on enterocytes in a proximal to distal direction. This was also indicated by electron microscope studies using rabbit PAP injected into the duodenum of 21-day-old fetuses. Such studies also provided evidence for the receptor-mediated translocation of IgG across the duodenum of the fetal rat in a manner similar to that described for older sucklings.
The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0 X 5-6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0 X 3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents.
The stimulated contractile function of aerobic isolated adult rat heart cells was assessed by laser light diffraction. Cells were maintained for up to 8 h by attachment to a cover slip and continuous perfusion in a chamber on the microscope stage. On stimulation such cells beat as though unattached. Cells showed a negative staircase which was reduced by increasing Ca or isoproterenol. Ryanodine caused a positive staircase on stimulation, which was enhanced by increasing Ca or isoproterenol or by using cells from younger rats. For beats of constant contraction duration, there was a linear relationship between the magnitude of cell shortening and the velocity of shortening, independent of the concentration of extracellular Ca. We conclude the following. 1) The beat characteristics of isolated cells are very similar to those of papillary muscle. 2) Attachment of cells need not alter their unloaded shortening characteristics. 3) Cells appear to contract against an internal load, to an extent determined by the degree of myofilament activation. 4) Cells from young rats require less extracellular Ca than those from adult rats for the same beat magnitude.
One hundred sixty patients with grade 1 transitional-cell carcinoma of the bladder were evaluated and treated at the Massachusetts General Hospital, Boston. The mean follow-up period was 57 months. There were 92 new patients and 68 patients who had a history of transitional-cell carcinoma. Fifty-three patients (33%) never had another transitional-cell carcinoma. Sixty-eight (43%) of the remaining 107 patients had recurrent Ta grade 1 transitional-cell carcinoma. In 32 patients (20%) disease progressed in grade, in seven patients (4%) invasive transitional-cell carcinoma developed, five patients underwent cystectomy, and one patient died of transitional-cell carcinoma. High-risk factors included positive results of cytologic studies after therapy and three or more recurrences. Multiple therapies were used, but it is impossible to determine if anything other than transurethral resection altered the course in these patients. The data suggest that patients with low-risk factors and Ta grade 1 tumors might be followed up with a quarterly cytologic examination and cystoscopy once or twice a year, unless a change in symptoms occurs.
Cells obtained from freshly resected human breast cancer were grown in vitro utilizing the soft agar technique. The effects of adding an antiestrogen (tamoxifen, TAM) and 17 beta-estradiol alone or simultaneously on cell growth were assessed. The addition of TAM (10(-6) M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%). The degree of inhibition caused by TAM was significantly higher in the ER-positive tumors that also contain the progesterone receptor (PgR) as compared to those that lacked that receptor (i.e., PgR negative) (46.2 +/- 2% versus 36.2 +/- 1.2% inhibition, P less than 0.01). The simultaneous addition of 17 beta-estradiol (10(-8) M) neutralized the inhibitory effect of TAM (10(-6) M) in the majority of tumors. With the presence of serum in the medium, the addition of 17 beta-estradiol alone resulted in an enhancement of cell growth in 6 of 17 tumors. However, because of the confounding effects of serum in the medium, we studied the individual effect of 17 beta-estradiol (10(-8) M) when added alone under serum-free conditions. Of 20 tumors studied, 17 beta-estradiol significantly enhanced cell growth in 12. There was a 67.8 +/- 12.6% increase in the number of colonies formed in these 12 responding tumors. One of these 12 responding tumors was ER negative as well as PgR negative, while the rest were all ER positive. These in vitro studies demonstrate that this approach can provide valuable information on endocrine mechanisms controlling the growth of human breast cancer.
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Minocycline, a broad-spectrum, highly lipid soluble tetracycline that has generated interest in the treatment of chronic prostatitis, was evaluated for its possible ability to be concentrated in benign prostatic hyperplasia. Drug levels in the prostate, plasma, fat, muscle and urine were measured in patients undergoing open prostatectomy after preoperative intravenous minocycline. The concentrations of the drug in the prostate and serum were close (4.16 versus 3.01 microgram. per gm.), while drug levels in striated muscle and fat were consistently lower (2.92 and 0.77 microgram. per gm). Higher preoperative doses of drug yielded higher tissue levels. Drug delivery closer temporally to the operation yielded higher serum and prostatic levels as opposed to striated muscle and fat, suggesting a rapid diffusion of the drug into benign prostatic hyperplasia.
The records of 30 patients who had suffered from vertebral osteomyelitis were reviewed. They conformed to a constant pattern, though varying in tems of: (i) the severity of the disease due to host-organism interrelationship; and (ii) age distribution. Causative organisms could not always be identifed, though all lesions settled with conservative measures of rest and antibiotics. A high proportion of the patients who were followed up for more than one year were back at work. The anatomical distribution of the lesions can be explained by our knowledge of the vascular supply to the vertebral bodies.