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Biomedical subjects

J Wass

Publications and source records attributed to J Wass.

At least 19 recordsLinked to original sources
PubMed2006

Use of physiological doses of human growth hormone in haematological patients receiving intensive chemotherapy promotes haematopoietic recovery: a double-blind randomized, placebo-controlled study.

In vivo and in vitro studies suggest human growth hormone (hGH) receptors on bone marrow stem cells may be biologically active and could be exploited to promote haemopoetic recovery after intensive chemotherapy. Patients with haematological malignancies receiving intensive chemotherapy and requiring hospitalization were randomized in a double-blind, placebo-controlled single-centre trial. Patients were randomly assigned to receive either hGH 500 microg/day or placebo, for 6 weeks. There was no significant difference in patient characteristics at baseline between the placebo and treatment arms. Patients treated with hGH showed significantly faster recovery of platelets to 25 x 10(9)/l (median of 16 versus 19 days; P = 0.03) compared to the placebo-controlled arm (hazard ratio 1.47 favouring hGH, 95% confidence interval (CI), 1.03-2.08). Time to relapse did not differ significantly between arms. There was no change in the anthropometric parameters at the start and end of hGH/placebo therapy. The study drug was well tolerated. Treatment with hGH in physiological doses improves platelet recovery, but is not associated with a lower relapse rate or improved anthropometric parameters in patients receiving intensive chemotherapy.

Adolescent↗
PubMed2002

Lymphoplasmacytoid lymphoma presenting as severe osteoporosis.

We report four cases presenting with severe osteoporosis which on further investigation were found to have an underlying lymphoplasmacytoid lymphoma (LPL). Common secondary causes of osteoporosis were excluded in each case. Three of the cases responded to treatment with a biphosphonate. As these lymphomas share some common pathological and clinical features with multiple myeloma (MM) an association with osteoporosis is likely to represent more than a coincidental finding. The incidence of osteoporosis occurring with LPL will become clearer if routine imaging is carried out in patients at presentation. Issues relating to the treatment of the osteoporosis as well as the lymphoma arise in patients that present in this way. Based on the model of bone disease in MM, correlating serum levels of osteoclast activating cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor (TNF) with the actual finding of bone disease provides a basis for future research into the pathogenesis and management of bone disease in these rare forms of low grade non-Hodgkin's lymphoma.

Aged↗
PubMed2002

Gender- and age-related differences in osteoclast formation from circulating precursors.

A number of bone diseases characterised by excessive osteolysis (e.g. osteoporosis and Paget's disease) exhibit a marked gender difference in prevalence and are more common in the elderly population. Bone resorption is carried out by osteoclasts, which are formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. In this study, we have determined whether there are gender- and age-related differences in osteoclast formation from circulating precursors. Peripheral blood mononuclear cells (PBMCs) were co-cultured with UMR106 osteoblast-like cells in the presence of macrophage-colony stimulating factor (M-CSF) and 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) or cultured alone in the presence of sRANKL (soluble receptor activator of nuclear factor kappa B ligand) and M-CSF. As assessed by the formation of tartrate resistant acid phosphatase (TRAP)-positive (TRAP(+)) and vitronectin receptor-positive (VNR(+)) multinucleated cells (MNCs), there was no difference in the number of circulating osteoclast precursors in males and females. Lacunar resorption carried out by osteoclasts formed from these precursors was generally increased in males compared with females (P=0.03). An increase in the number of TRAP(+) and VNR(+) MNCs formed from male PBMCs was noted in response to 1,25(OH)(2)D(3) (P<0.005). An increase in lacunar resorption in cultures of PBMCs (10(5) per well) from males was also noted in response to 10(-9) M 1,25(OH)(2)D(3) (P<0.05) and sRANKL (P=0.05), but not M-CSF. The addition of dexamethasone resulted in a marked increase in osteoclast formation and lacunar resorption in both males and females. Post-menopausal females and males of comparable age showed similar levels of osteoclastogenesis. Pre-menopausal women showed similar levels of osteoclastogenesis but less resorption (P=0.01) compared with males of comparable age. These results show that there are specific gender/age-related differences in osteoclast formation and bone resorption and have implications for evaluating osteoclastogenesis in skeletal diseases such as primary osteoporosis and Paget's disease.

Adult↗
PubMed2000

Criteria for cure of acromegaly: a consensus statement.

In February 1999, a workshop was held in Cortina, Italy to develop a consensus defining the criteria for cure of acromegaly. The workshop was sponsored by the University of Brescia and hosted by the Italian Society of Endocrinology. Invited international participants included endocrinologists, neurosurgeons, and radiotherapists skilled in the management of acromegaly. This statement summarizes the consensus achieved in these discussions.

Acromegaly↗
PubMed1999

Respiratory muscle strength in Cushing's syndrome.

The effect of Cushing's syndrome on respiratory muscle strength is unknown. Therefore, we studied 10 consecutive patients with severe Cushing's syndrome. The respiratory muscles were assessed using maximal inspiratory and expiratory mouth pressures (MIP, MEP), maximal sniff transdiaphragmatic pressures (max sniff Pdi), and maximal sniff esophageal pressures (max sniff Pes). Maximal quadricep strength was also assessed. The patients demonstrated an overall mean MIP 92 cm H(2)O, SD 19 (mean 105% of predicted; SD, 23%), mean MEP 134 cm H(2)O, SD 35 (mean 99% of predicted; SD, 25%), mean max sniff Pdi 107 cm H(2)O, SD 12 (mean 78% of predicted; SD, 10%) and mean max sniff Pes of 92 cm H(2)O, SD 11 (mean 92% of predicted; SD, 11%). Quadriceps muscle strength was reduced in all 10 patients: mean 26 kg, SD 9 (mean 49% of predicted strength, SD 21%). Respiratory muscle weakness was not found, despite the presence of severe quadriceps impairment. We conclude that major weakness of the respiratory muscles is not usual in Cushing's syndrome.

Adult↗
PubMed1995

Malignant degeneration of a mature cystic teratoma five decades after discovery.

Malignant degeneration of mature cystic teratomas has been reported in 1-3% of cases. A patient with the unusual occurrence of a stage IIIC squamous cell carcinoma arising in a mature teratoma over 50 years after initial diagnosis is presented. The patient was treated with pelvic radiotherapy. The role of serum squamous cell carcinoma antigen in detecting degeneration of mature cystic teratomas at an early stage is considered.

Aged↗
PubMed1995

A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome.

OBJECTIVE: The diagnosis of Cushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single in-patient sleeping midnight cortisol to a standard 48-hour in-patient low-dose dexamethasone suppression test (LDDST) during the same admission. DESIGN: A retrospective analysis was performed on 150 patients investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Cushing's syndrome. PATIENTS: One hundred and fifty patients with a diagnosis of Cushing's syndrome were analysed: 110 with Cushing's disease; 12 with tumours with ectopic ACTH secretion; 8 with ACTH dependent Cushing's syndrome of so far undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with adrenocortical nodular hyperplasia. Twenty normal volunteers and nine patients with non-endocrine conditions were also investigated as controls. MEASUREMENTS: Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prior to this date. RESULTS: In all the control subjects the sleeping midnight cortisol was < 50 nmol/l, below the lowest standard of the routine in-house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70-2000 nmol/l. In contrast, in three cases, all of whom had proven Cushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to < 50 nmol/l following the LDDST. CONCLUSION: In this series of 150 cases, a single in-patient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly different from normal subjects. In contrast, the low-dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in-patient. We recommend that a low-dose dexamethasone suppression test should not be used alone for confirmation of Cushing's syndrome since it may miss 2% of cases.

Adolescent↗
PubMed1994

Karyotypic analysis of a heterogeneous human transitional cell carcinoma of the bladder.

The UCRU-BL-17 (BL-17) series of xenografts, tissue culture sublines, and cloned cell lines (Fig. 1) shows a range of heterogeneous growth characteristics both in vitro and in vivo (Table 1) and represents a model of human bladder cancer heterogeneity. Cytogenetic analysis was undertaken to determine if specific chromosome changes correlated with particular aspects of the heterogeneous phenotypes. The BL-17 sublines and cloned cell lines shared many common chromosome abnormalities. Indeed, the cloned cell lines showed nearly identical karyotypes despite their marked differences in growth characteristics. Karyotypic evolution with passage through the nude mice was apparent, however. This evolution occurred at the specific chromosome regions of 1p12, 3cen-3p21, and 6cen-6q21. Whether the heterogeneity of karyotype between the BL-17 cell lines resulted from the existence of multiple clones in the original patient tumor or from karyotypic instability through passage in nude mice is uncertain, but in either case the specificity of karyotypic evolution observed suggests that 1p12, 3cen-3p21, and 6cen-6q21 are hotspots for rearrangement in the BL-17 tumor. No specific correlations between chromosome abnormalities and biologic characteristics could be made, but several unique karyotypic features arose in the progression to two of the sublines, BL-17/23 alpha and BL-17/0/X2A, coinciding with a loss of anchorage-independent growth by BL-17/23 alpha and a change in growth in vivo from a solid tumor to a fluid-filled tumor by BL-17/0/X2A.

Aged↗
PubMed1993

Translocation (Y;1)(q12;q21) in acute leukemia.

This report documents one patient with myelodysplasia evolving into acute leukemia who showed a t(Y;1) translocation confirmed by in situ hybridization. Most of the q arm of the Y chromosome was translocated to an additional q arm of chromosome 1, resulting in trisomy 1q. To our knowledge only four other cases with this t(Y;1) have been reported.

Adult↗
PubMed1993

Undergraduate medical education.

Pressures from students and teachers, from professional bodies, and from changes in the way health care is delivered are all forcing a rethink of how medical students should be taught. These pressures may be more intense in London but are not confined to it. The recommendation the Tomlinson report advocates that has been generally welcomed is for more investment in primary care in London. General practitioners have much to teach medical schools about effective ways of learning, but incentives for teaching students in general practice are currently low, organising such teaching is difficult and needs resources, and resistance within traditional medical school hierarchies needs to be overcome. Likewise, students value learning within local communities, but the effort demanded of public health departments and community organisations is great at a time when they are under greater pressure than ever before. The arguments over research that favour concentration in four multifaculty schools are less clear cut for undergraduate education, where personal support for students is important. An immediate concern is that the effort demanded for reorganising along the lines suggested by Tomlinson will not leave medical schools much energy for innovating.

Community Medicine↗
PubMed1993

Heat-shock gene expression and cell cycle changes during mammalian embryonic development.

Synchronized regulation of cell division during gastrulation is essential for the regional proliferation of cells and pattern formation of the early CNS. The neural plate and neuroectoderm cells are a rapidly dividing and differentiating population of cells with a unique and rapid heat-shock response. Heat shock and the heat-shock genes were studied during neural plate development in a whole rat embryo culture system at 9.5-11.5 days. A lethal shock can cause cell death and severe developmental defects to the forebrain and eye during organogenesis. Heat shock can also result in acquired thermotolerance whereby cell progression is delayed at the G1/S and S/G2 boundaries of the cell cycle. This delay in cell cycle progression caused an overall lengthening of the cell cycle time of at least 2 hr. The heat shock genes may therefore function as cell cycle regulators in neuroectoderm induction and differentiation. The kinetics and expression of the hsp genes were examined in neuroectodermal cells by flow cytometry and Northern analysis. The levels of hsp mRNA 27, 71, 73, and 88 were identified following exposure at 42 degrees C (nonlethal), 43 degrees C (lethal) and 42 degrees/43 degrees C (thermotolerant) heat shock. Examination of hsp gene expression in the neural plate showed tight regulation in the cell cycle phases. Hsp 88 expression was enhanced at Go and hsp71 induction at G2 + M of the cell cycle. Cells exposed to a thermotolerant heat shock of 42 degrees C induced hsp71 mRNA expression in all phases of the cell cycle with the mRNA levels of hsp27, 73, and 88 increased but relatively constant. Following a lethal heat shock, dramatic changes in hsp expression were seen especially enhanced hsp71 induction in late S phase. The regulated expression of hsps during the cell cycle at various phases could play a unique and important role in the fate and recovery of neuroectoderm cells during early mammalian embryo development.

Animals↗
PubMed1993

Characterization of a new human bladder cancer cell line, UCRU-BL-28.

A new human bladder cancer cell line, UCRU-BL-28 has been established and characterized from a relapsed, cisplatin resistant, grade II, stage T4 tumor. This line is tumorigenic in nude mice and reflects the pathology of the original tumor. The morphology, the expression of tumor-associated antigens and EGF receptors, and the ability to grow both in an anchorage independent manner and in the absence of serum is explored. The BL-28 line has 71-74XXY chromosomes, with del 5q, der(9) and i(19q). Further studies on the molecular basis of bladder cancer, chemosensitivity to cisplatin, growth factor production and tissue invasion are under way.

Biomarkers, Tumor↗
PubMed1991

Inhibitory effect of norcantharidin on K562 human myeloid leukemia cells in vitro.

Mylabris, the dried body of the Chinese blister beetle, has been used as a Chinese medicinal for over 2000 years. Its active constituent, cantharidin, has antitumor properties and causes leukocytosis. Norcantharidin (NCTD), the demethylated form of cantharidin, is easier to synthesize and is less toxic. NCTD irreversibly reduced the clonogenic efficiency of parental and drug-resistant K562 sublines, with drug-resistant sublines showing greater susceptibility to NCTD than parental cells. NCTD inhibited DNA synthesis by blocking cells at the G2/M phase of the cell cycle. The data suggest that NCTD may be suitable in the treatment of drug-resistant leukemia.

Antineoplastic Agents↗
PubMed1989

Cytogenetic abnormalities in benign lymphoid hyperplasia: a dual-parameter study using chromosome analysis and flow cytometry.

This is a prospective study of lymphoid tissue showing benign reactive hyperplasia (18 lymph nodes and 2 tonsils), using cytogenetic analysis of cells stimulated with T- or B-cell mitogens. The reason for this study was the detection of an abnormal chromosomal population in cells from an enlarged lymph node excised from a 7-year-old female who on further investigation was found to be clinically well and after one year's close follow-up had not developed any further signs or symptoms of malignancy. In addition, DNA content was measured by flow cytometry (FCM) on fresh cell suspensions in 17 cases and fixed cell suspensions in 3 cases. Structural and numerical clonal chromosome abnormalities were found in 9 of the 20 samples, but no common specific defect was identified. FCM showed an abnormal DNA content in 10 of the 20 samples studied; 3 of these showed clonal chromosome abnormalities. Surface membrane immunoglobulin studies were carried out on 15 of the 20 samples using cell suspensions and frozen tissue sections. In 5 of the 15 cases, monoclonal surface immunoglobulin was detected. There was no direct correlation between the surface membrane immunoglobulin studies and the chromosome and FCM analyses. We conclude that aneuploidy is a common feature in reactive lymphoid tissue, but both cytogenetics and FCM are needed to identify it.

Aneuploidy↗
PubMed1989

Characterization of cell lines derived from a multiply aneuploid human bladder transitional-cell carcinoma, UCRU-BL-13.

A series of cultured cell lines (designated UCRU-BL-13) has been established from different serial passages of a multiply aneuploid human bladder transitional-cell carcinoma xenografted in nude mice. Serial passage of the xenografts in vivo and of the cell lines in vitro was accompanied by shifts in the tumor ploidy, with dominance of different major peaks. Despite this, the expression of tumor markers remained constant, and consistent chromosomal markers were observed both in the 8th xenograft passage and in a subline in tissue culture established over a year apart. Chromosomal numbers reflected the predominant aneuploid peaks observed; consistent numerical and structural changes included a marker derived from chromosome 1, 8p-, -10, 11q+, and 17q+. The cell line derived from the initial xenograft comprised a mixture of transitional, adenocarcinoma and squamous carcinoma cells in early passage, but adenocarcinoma cells were absent from later passages. The lines expressed the B-blood-group antigen, histocompatibility antigens, receptors for transferrin and EGF, and reacted with a series of monoclonal antibodies (MAbs) directed to malignant human epithelial cell lines. These lines provide a model for studying the evolution of tumor heterogeneity and drug resistance in bladder carcinoma exhibiting multiple aneuploidy.

Aneuploidy↗
PubMed1989

Site-specific growth of the prostate xenograft line UCRU-PR-2.

A xenografted small-cell, undifferentiated prostate (SCUCP) cancer line, UCRU-Pr-2, was implanted at different sites within nude mice to examine the effect of local environmental factors on tumor growth and behavior. All tumors that grew were small-cell carcinomas. Fragments implanted within muscle and under the kidney capsule were locally invasive; however, tumors that grew subcutaneously or intraperitoneally showed no invasion. UCRU-Pr-2 did not grow in the spleen or the liver. No induced metastases were observed in the lung after intravenous injection. The sites of implantation did not allow the outgrowth of subpopulations as detected by the parameters used: light and electron microscopy, expression of tumor markers, levels of hormone production, and DNA flow cytometry. Electron microscopy, which showed both glandular and neuroendocrine differentiation within the same cell, does not support a dual-cell origin of SCUCP.

Animals↗