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Biomedical subjects

J Brooks

Publications and source records attributed to J Brooks.

At least 73 records · Page 4Linked to original sources
PubMed1995

Distribution of 239,240Pu and 238Pu concentrations in sediments from the Ob and Yenisey Rivers and the Kara Sea.

The major sources of plutonium isotopes in the environment are from nuclear weapons testing via global and close-in (debris) fallout, nuclear fuel reprocessing and fabrication plant effluents. Measurements of differences in the Pu isotopic ratios (239Pu/240Pu, 238Pu/239,240Pu and 241Pu/239,240Pu) have yielded information not only on the time horizons for sedimentary deposits but also on the sources of Pu. We have measured 238Pu, 239,240Pu and 137Cs concentrations in the surficial sediments of the Ob and Yenisey Rivers (Russia) and the Kara Sea. The downcore variations of 238Pu and 239,240Pu concentrations have also been measured in some sediment cores. A comparison of the sediment core inventories of 239,240Pu along with the 238Pu/239,240Pu activity ratios with those expected from global fallout at the study sites allows us to estimate the relative amounts of reactor-derived 238Pu and 239,240Pu from the dumped reactor sites in the study area. In surficial sediment samples, the 239,240Pu concentrations vary between 9.4 and 627 mBq kg-1, with a mean of 250 mBq kg-1. The 238Pu/239,240Pu activity ratios vary between 0.009 and 0.065 with an average value of 0.034 +/- 0.003. This range can be compared to the average 238Pu/239,240Pu activity ratio of 0.030 for the year 1993 from nuclear weapons testing and SNAP fallout obtained from soil studies, indicating very little additional sources of 238Pu to the sediments in the study area. In sediment cores, the maximum depths at which 239,240Pu was detected varied between 6 and 12 cm. These depths yield average apparent sedimentation rates in the coastal Kara Sea between 1.5 and 3.0 mm yr-1 (assuming Pu input since 1952, and no sediment mixing).

Arctic Regions↗
PubMed1995

The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation.

Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbaric oxygen and carbogen. R3230Ac mammary adenocarcinomas were implanted into Fisher 344 rats. Arterial blood gases, blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres; atm) 100% oxygen, normobaric carbogen or hyperbaric (3 atm) carbogen (HBC) +/- bretylium. HBO reduced the mean level of low pO2 values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO2 values from 0.82 to 0.51 (P = 0.002) an increased median pO2 from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Sympathetic-mediated vasoconstriction during hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobaric carbogen breathing.

Adenocarcinoma↗
PubMed1995

Phase II study of carboplatin and continuous infusion bleomycin followed by cisplatin and 5-fluorouracil in recurrent head and neck cancer.

BACKGROUND: Recurrent squamous cell carcinoma of the head and neck is poorly responsive to most chemotherapy regimens. Carboplatin and bleomycin are effective single agents with non-overlapping toxicity; therefore, we sought to explore the efficacy of this regimen in a phase II study. In the second stage of the study, patients who did not respond to carboplatin and bleomycin were given treatment with cisplatin and 5-fluorouracil (5-FU). PATIENTS AND METHODS: Patients with recurrent squamous cell carcinoma of the head and neck were treated with carboplatin 400 mg/m2 followed by bleomycin 15 units intravenously as a continuous infusion for 4 days. Patients with no tumor response after 3 cycles of carboplatin and bleomycin were crossed-over to receive cisplatin 100 mg/m2 and 5-FU 1000 mg/m2/day continuous infusion for 5 days. RESULTS: Among the 20 carboplatin-bleomycin patients evaluable for toxicity, no cases of grade 4 granulocytopenia were reported and grade 3 or 4 thrombocytopenia developed in only three patients. Three partial responses occurred among the 19 patients (16%) [95% C.I. 0% to 32%] evaluable for response to carboplatin-bleomycin. None of the 11 patients crossed-over to cisplatin and 5-FU had a major response. CONCLUSION: The combination of carboplatin and bleomycin is well tolerated in patients with recurrent head and neck cancer, but the activity does not appear to be superior to the activity of either agent alone. Patients who did not respond to carboplatin and bleomycin were also resistant to the cisplatin and 5-FU regimen.

Adult↗
PubMed1995

The relationship between decidualization and prolactin mRNA and production at different stages of human pregnancy.

Within the human utero-placental unit only decidualized stromal cells express mRNA for prolactin. However, it is not clear if the level of prolactin production is related to the number of decidualized cells or the capacity of individual decidual cells to synthesize prolactin, either or both of which parameters may change during pregnancy. In the present study, prolactin production at different stages of human pregnancy was examined using quantitative in situ hybridization to assess decidual prolactin mRNA abundance, immunocytochemistry to examine the prolactin content inside decidual cells and RIA to measure decidual prolactin output into amniotic fluid. Throughout pregnancy the proportion of stromal cells showing positive immunostaining and mRNA for prolactin increased. There was a parallel increase in decidual cell size which was correlated with an increase in prolactin gene expression and intensity of immunostaining for prolactin in individual decidual cells. These changes in decidual cells were consistent with the changes in the concentration of prolactin in amniotic fluid. These results suggest that there is a close link between the level of prolactin gene expression and production of prolactin by individual decidual cells, which in turn is directly related to the process of decidualization that continues throughout human pregnancy.

Amniotic Fluid↗
PubMed1995

Variable histology of anastomotic biopsies with detectable prostate specific antigen after radical prostatectomy.

Progressive elevation of the prostate specific antigen (PSA) level after radical prostatectomy for adenocarcinoma is generally considered as irrefutable evidence of recurrent tumor. We assessed the results of 62 biopsies of the vesicourethral anastomosis in 41 men who had 3 or more consecutive PSA levels of 0.4 ng./ml. or greater after radical prostatectomy and no evidence of metastatic disease. The median PSA at the time of the first biopsy was 2.2 ng./ml. (range 0.4 to 50). Histological confirmation of recurrent cancer was established after 1 biopsy procedure in 39% of the patients and after 1 or more biopsy procedures in 59%. Biopsy was positive in 78% of 23 patients with an abnormal digital rectal examination, 40% of 5 with an abnormal transrectal ultrasound only, and 23% of 13 with a normal digital rectal examination and ultrasound. Among the patients with and without biopsy proved tumor recurrence there were no significant differences between the pathological stage or histological grade of the primary tumors, the month after surgery of the first detectable PSA level, the PSA doubling time, the month after surgery of the positive biopsy or the last negative biopsy, and the PSA level at the time of the positive biopsy or the last negative biopsy. In 6 cases benign prostatic tissue only was recovered from 1 or more biopsy specimens. This experience demonstrates that in patients with a detectable PSA after radical prostatectomy recurrent cancer may be difficult to document by biopsy of the vesicourethral anastomosis.

Anastomosis, Surgical↗
PubMed1994

T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.

Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11-restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11-positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.

Amino Acid Sequence↗
PubMed1994

Superovulation and embryo recovery in ewes treated with gonadotrophin-releasing hormone agonist and purified follicle-stimulating hormone.

Chronic treatment with gonadotrophin-releasing hormone (GnRH) agonist eliminates luteinizing hormone (LH) pulses and inhibits maturation of Graafian follicles in sheep. Since the presence of 'dominant' follicles may inhibit superovulatory responses, an experiment was conducted to determine whether a GnRH agonist could be used in conjunction with follicle-stimulating hormone (FSH) to induce a superovulatory response with production of normal embryos. Twenty-four Welsh Mountain ewes were chronically treated with GnRH agonist by means of a subcutaneous minipump. Twelve of the ewes were given 12 mg progesterone intramuscularly (i.m.) twice daily for four days; all ewes were then given 672 micrograms (total) of highly purified FSH continually infused intravenously for either 72 h (Group A) or 96 h (Group B) in a 2 x 2 experimental design (n = 6). Ovulation was then induced with 750 I.U. human chorionic gonadotrophin injected i.m. (Day 0) and all ewes were inseminated into the uterus with > 100 x 10(6) fresh sperm on Day 0. Embryos were flushed from the uterus, and ovaries were inspected at laparotomy on Day 5. Pretreatment with progesterone did not affect any of the parameters measured and data were pooled accordingly. There were no differences between Groups A and B in the number of ovulations or the number of embryos recovered, although there were more large unruptured follicles in Group A animals (8.8 +/- 0.8 v. 3.1 +/- 0.7, P < 0.001). The embryo recovery rate was higher in Group A ewes (52.5 v. 26.4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regulation of gonadotrophin-releasing hormone receptor mRNA expression in the sheep.

To investigate the regulation of the sheep gonadotrophin-releasing hormone receptor (GnRH-R) gene expression, two different treatment regimes were used. Experiment 1 examined the effects of twice daily injections of ovine follicular fluid (oFF, 1.5 ml s.c.) as a source of inhibin, and daily GnRH antagonist injections (Nal-Glu.HOAc, 2 mg s.c.) on days 9-12 of the oestrous cycle. Luteolysis was induced on day 12 with prostaglandin (PG) and the ewes killed at two different stages; day 12 (luteal) and 18 h after PG injection. Experiment 2 examined the effect of a single injection of oestradiol benzoate (100 micrograms i.m.) 18 h before death in luteal phase ewes and ewes chronically implanted with the GnRH agonist, buserelin. In both experiments, pituitaries were removed at death for determination of pituitary GnRH binding, LH content and levels of GnRH-R and LH beta mRNA. In addition in experiment 1, follicles > or = 2.5 mm were dissected from the ovaries for determination of oestradiol content. In experiment 1, oFF treatment during the luteal phase completely inhibited follicle oestradiol production but was without effect on the other parameters measured. After cessation of oFF treatment and induction of luteolysis, a significant (P < 0.05) increase in plasma LH occurred but the normal follicular increase in both GnRH-R mRNA levels and GnRH binding seen in control ewes was prevented. GnRH antagonist treatment alone or in combination with oFF also inhibited follicle oestradiol production, prevented the increase in GnRH-R mRNA, completely inhibited GnRH binding and significantly decreased LH beta mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Immunophenotypic differences between putative hematopoietic stem cells and childhood B-cell precursor acute lymphoblastic leukemia cells.

Acute leukemia cells express myeloid, B-lymphoid and T-lymphoid lineage specific antigens. Many acute leukemias express the hematopoietic progenitor cell antigen CD34. Three proposed models of the normal human hematopoietic stem cell include CD34+ Thy-1low Lin-, CD34+ CD38-, and CD34+ HLA-DR-. The patterns of expression of CD34, Thy-1, CD38, HLA-DR, and multiple lineage-specific antigens on 49 consecutive pediatric B-cell precursor acute lymphoblastic leukemia (ALL) cases submitted for immunophenotyping (36 at first diagnosis, 13 at relapse) were analyzed. CD34+ expression was observed in 67% of the cases. CD34+ expression correlated with Thy-1low expression and expression of myeloid antigens (p < 0.001 and < 0.025, respectively). The CD34+ Thy-1low phenotype was observed in 65% of the cases; the CD34+ CD38- or CD34+ HLA-DR- phenotypes were observed in only three cases. Examples of heterogeneous expression of CD34 and Thy-1 were found in six cases, but CD38 expression was always bright and homogeneous in all positive cases. The data from this analysis indicates that the CD34+ CD38- or CD34+ HLA-DR- phenotypes would be more useful than the CD34+ Thy-1low phenotype for distinguishing normal hematopoietic stem cells from leukemic cells in childhood B-cell precursor ALL.

ADP-ribosyl Cyclase↗
PubMed1994

Interleukin-11 expression in donor bone marrow cells improves hematological reconstitution in lethally irradiated recipient mice.

Lethally irradiated mice were transplanted with syngeneic bone marrow cells infected with a recombinant retrovirus vector containing the human interleukin-11 (hIL-11) cDNA under the control of the human cytomegalovirus (CMV) immediate early promoter. The hIL-11 RNA transcript from the vector was detected in the spleen and bone marrow of the recipient mice, and hIL-11 protein accumulated in their serum. The hematological reconstitution of these mice was compared with recipient mice rescued with bone marrow infected with the parental retrovirus vector not containing the hIL-11 cDNA. The hIL-11-expressing mice had an accelerated recovery of circulating platelets and red and white blood cells. Three months after the transplantation, bone marrow was harvested from the mice and used to rescue other lethally irradiated recipients. The hIL-11 mRNA and protein were also detected in these secondary recipients, and the mice showed improved hematological reconstitution relative to a control group. No abnormal cell proliferation or other histopathology was observed in the hIL-11-expressing mice.

Animals↗