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Biomedical subjects

S Walter

Publications and source records attributed to S Walter.

At least 19 recordsLinked to original sources

Monocyte chemotactic cytokine gene transfer modulates macrophage infiltration, growth, and susceptibility to IL-2 therapy of a murine melanoma.

Tumor-derived chemotactic factors have been identified and suggested to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of a tumor-derived chemotactic factor molecularly identified as monocyte chemotactic protein (MCP; alternative designations are JE and MCAF) by gene transfer in a murine melanoma. After gene transfer, MCP-producing melanoma clones showed a marked (twofold) increase in the percentage of tumor-associated macrophages compared with control clones and with the parent line: for instance, the percentage of tumor-associated macrophages was 20.9 +/- 1.5, 29.4 +/- 2.3, and 47.6 +/- 2.5 for the parent line, the control V14 clone, and the MCP-producing L12 clone, respectively. MCP-producing cells were tumorigenic but exhibited a slower growth rate in vivo (e.g., doubling time of 2.9 and 6.6 days for the control V14 and the MCP-producing L12 clone, respectively) with a prolongation of survival time. The in vitro growth rate of melanoma clones was unaffected by MCP gene transfer. The same difference between MCP-producing and control cells, in terms of macrophage infiltration and growth rate, was detected after implantation in athymic mice. Whereas the in vivo growth rate of MCP-expressing tumors was slower, after i.m. inoculation of small cell numbers (10(2) cells) MCP-producing cells were slightly, but significantly, more tumorigenic. Local administration of IL-2 had modest, but definite, antitumor activity in this model; MCP-producing cells were less susceptible to local IL-2 immunotherapy. These results demonstrate that a tumor-derived chemotactic cytokine can indeed play a role in the regulation of mononuclear phagocyte recruitment in neoplastic tissues and emphasize how tumor-associated macrophages can exert a dual influence in tumor-host interactions.

Animals

The gene encoding the cellulase (Avicelase) Cel1 from Streptomyces reticuli and analysis of protein domains.

Streptomyces reticuli produces an unusual cellulase (Avicelase), with an apparent molecular weight of 82 kDa, which is solely sufficient to degrade crystalline cellulose. During cultivation the processing of the Avicelase to a truncated enzyme (42 kDa) and an inactive protein (40 kDa) correlated with the occurrence of an extracellular protease. After its purification this 36 kDa protease cleaved the S. reticuli Avicelase in vitro in the same manner. Using antibodies raised against the Avicelase and its truncated form (42 kDa) and gene libraries of S. reticuli DNA in the Escherichia coli phage vectors lambda gt11 and Charon 35, the Avicelase gene (cel1) was identified. Further subcloning and DNA-sequencing revealed a G+C rich (72%) reading frame of 2238 bp encoding a protein of 746 amino acids. The transcriptional start site was mapped about 180 bp upstream from the GTG start codon. A signal sequence of 29 amino acids was identified by aligning the deduced amino acids with the characterized N-terminus of the 82 kDa Avicelase. Comparison of the N-terminal amino acids from the purified proteins with the amino acid sequence derived from the Avicelase gene revealed that the truncated enzyme (42 kDa) corresponds to the C-terminal region whereas the inactive proteolytically derived protein (40 kDa) represents the N-terminal part of the 82 kDa Avicelase. Comparisons with amino acid sequences deduced from known cellulase genes indicated the presence of three putative protein domains: (i) an N-terminal part showing significant similarity with a repeat region of endoglucanase C from Cellulomonas fimi, recently shown to be a cellulose-binding domain; (ii) an adjoining region sharing homology with the N-terminal domains with unknown function of endoglucanase A from Pseudomonas fluorescens, endoglucanase D from Clostridium thermocellum and a cellodextrinase from Butyrivibrio fibrisolvens, and (iii) a C-terminal catalytic domain belonging to cellulase family E.

Amino Acid Sequence

Hypothermia, Wernicke encephalopathy and multiple sclerosis.

Neurological exacerbation observed in MS patients is usually related to a demyelinating process. We report two patients where hypothermia (32.4 degrees C and 32.5 degrees C) and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). The clinical features and the rapid efficiency of parenteral thiamine were suggestive of WE. Hypothermia is an exceptional symptom observed in MS and has been considered as resulting from hypothalamic demyelination; these two cases showed that WE which is another cause of reversible hypothermia, can be associated with MS.

Body Temperature Regulation

Transurethral prostatectomy compared with incision of the prostate in the treatment of prostatism caused by small benign prostate glands.

In a prospective, randomized study 60 patients with prostatism caused by small prostate glands (estimated weight < 20 g) had either transurethral prostatectomy (TURP, n = 31) or transurethral incision of the prostate (TUI, n = 29). Operating time and blood loss were significantly less in the group that underwent TUI. There were no differences between the groups in number of days with an indwelling catheter or days in hospital after operation. Eight patients in the TUI group required further operation, as did four in the TURP group, one of whom was discharged with a permanent indwelling catheter. In addition one patient developed a urethral stricture. Nine of the failures of treatment occurred within the first month. Fifty-one patients were followed up at 3 months and 47 were also seen at 12 months. Both operations significantly improved symptom scores and maximum flow rates compared with preoperatively, but the improvement in maximum flow rate was significantly better in the TURP group than in the TUI group. At 12 months TURP had also improved micturition time and voided volume, which TUI had not. Neither operation caused any significant change in sexual activity or erective potency postoperatively. Retrograde ejaculation was, however, seen in more than half of the patients in the TURP group, and only one in the TUI group. We recommend TUI for the treatment of prostatism caused by small prostate glands in patients who want to preserve normal ejaculation or are at poor surgical risk.

Aged

Cigarette smoking and pressure-volume characteristics of the lung.

This study was done to identify the immediate changes induced by cigarette smoking on the mechanical properties of the lung. Static compliance (C stat), static pressure-volume (Stat P-V) hysteresis, vital capacity (VC), frequency dependence of dynamic compliance (C dyn) and collateral ventilation (Coll V) of the lung were studied in six mongrel dogs. The smoking of one cigarette induced a fall in VC and static P-V hysteresis of the lungs. These changes indicate an increase in elastic recoil of the lung probably caused by inactivation of pulmonary surfactant. Frequency dependence of C dyn did not develop after smoking. Extensive collateral ventilation was seen in the lungs of all the experimental animals and in those of five other normal dogs, who had not been exposed to cigarette smoke. The significance of these findings are discussed.

Animals

Bronchial lability in allergic rhinitis.

The aim of this study was to assess the relationship between exercise bronchial lability and the changes in pulmonary function over a one year period in allergic rhinitis. Eighty four nonsmoking male medical students of whom twenty two were allergic rhinitics were studied. Pulmonary function status was significantly lower and exercise bronchial lability significantly higher in the allergics. Over a one year period the mean decline in the forced expiratory volume in one second (FEV1) was three times greater and in the forced expiratory flow rate in the middle half of the vital capacity (FEF 25-75%) 50% greater among the allergics. The change in FEV1 was positively related to the bronchial lability, indicating that greater bronchial lability was associated with less decline in pulmonary function in these subjects.

Adolescent

Blood basopenia as an indicator of ovulation.

Direct basophil counts were done on capillary blood samples in thirteen normal young women, during the different phases of their menstrual cycles. Mean basophil counts during the follicular and progestational phases were 36.6/cumm and 39.3/cumm respectively. A significant midcycle fall in counts of 36% and a premenstrual fall of 22% were observed. These changes are probably due to migration of the cells from the peripheral blood into the rupturing follicle of the ovary and into the ischemic premenstrual endometrium.

Adolescent

Macrophage infiltration and growth of sarcoma clones expressing different amounts of monocyte chemotactic protein/JE.

Tumor-derived chemotactic factors (TDCF) have been identified and thought to play a role in the regulation of macrophage infiltration in neoplastic tissues. The present study was designed to assess the in vivo relevance of the TDCF molecularly identified as monocyte chemotactic protein/JE, by investigating murine sarcoma clones expressing different levels of MCP/JE. The 1D3 clone derived from the B77 RSV-induced sarcoma expressed appreciable levels of MCP/JE mRNA and, concomitantly, chemotactic activity for mononuclear phagocytes. In contrast, the 5B11 clone from the same tumor had undetectable levels of MCP/JE transcripts and little or no chemotactic activity. The chemotactic activity of 1D3 cells was blocked by an appropriate specific antiserum. The in vitro growth rate of the 2 sarcoma lines was identical. Upon in vivo transplantation, the 1D3 clone showed a substantially higher level of tumor-associated macrophages (28.9%; range 21%-34%) than the 5B11 clone (16.6%; range 13%-20%). 5B11-induced tumors appeared earlier and grew faster than those induced by 1D3. The difference in growth rate and in macrophage infiltration between 1D3 and 5B11 clones was also evident upon transplantation into nude mice. These results are consistent with the hypothesis that TDCF, identified as MCP/JE, is one important determinant of macrophage infiltration in tumors.

Animals

[One year of experience with pulsed dye laser treatment of ureteral calculi].

During a period of one year, 18 patients with symptom-producing ureteric stones were treated with ureteroscopic laser lithotripsy. Pulsed dye laser was employed through a rigid ureteroscope. The laser emits impulses lasting for 2 microseconds with a wave-length of 504 nm. In 11 patients (61%), satisfactory disintegration could be observed and two further patients could be freed from stones by dormia extraction. In three patients treatment was concluded with ultrasound and two with ESWL = extracorporeal shock wave lithotripsy. Three slight perforations of the ureter did not require treatment apart from routine relief by a ureteric catheter or stent. With new thinner scopes, the technique can be simplified, trauma in the ureter reduced and the need for preparation of the ureter eliminated.

Adult

[Experience from the first year of treatment of renal calculi with extracorporeal piezoelectric shockwave lithotripsy].

The experience of the first year with piezoelectric extracorporeal lithotripsy is described. One hundred and eighty-eight patients commenced treatment of 194 renoureteric stone units (a total of 328 stones). Twelve per cent required analgesics during therapy. The median number of treatments was two (1-6) and median number of shock waves 4,200 (450-24,606). One hundred and twenty-three stone units had concluded treatment and control schedules at the follow up end date. After six months, 59% of the stone units were stone-free, while 17% had residual fragments up to 2 mm, and additional 15% had residual fragments between 2 and 6 mm. Only few and insignificant complications were observed. Extracorporeal shock wave lithotripsy by the Wolf Piezolith 2300 is a well-tolerated, effective, relative painless and not complicated treatment of renal stones, and an important part of modern treatment of staghorn- and ureteric stones.

Adult

[Prostatic hypertrophy: natural history. Subjective and objective changes during a 6-month period].

Out of 30 patients, referred consecutively, with symptomatic and urodynamic signs of benign hypertrophy of the prostate, 22 were observed for six months as regards symptom scoring, urine flow measurements, serum creatinine and culture from the urine. After the period of observation, 1/3 of the patients no longer wanted operation on account of subjective improvement. The symptom scoring in this group was significantly lower (p less than 0.01) than in the group which was subsequently submitted to operation, on the other hand, no difference in urine flow was demonstrated. No statistically significant alteration in symptom scoring or urine flow was observed during the period of observation but both parameters showed fluctuations. The variations in flow were no greater than in men with normal micturition. None of the patients developed acute retention or involvement of upper urinary tracts during the period of observation. This investigation speaks for a more observing attitude towards treatment of benign hypertrophy of the prostate. In cases where no absolute indications for operative treatment are present (episodes of retention of urine or involvement of the upper urinary tracts), the patient's subjective symptoms constitute an important factor in the indications for operation.

Aged

Psychosocial impacts in populations exposed to solid waste facilities.

This interdisciplinary study uses a parallel case study design to investigate psychosocial impacts in populations exposed to three solid waste facilities in Southern Ontario. Impacts are examined at three social scales: individual, social network and community levels. The objectives and design derive from a feasibility study recently completed by the same research team. A two stage approach is adopted. The first is an epidemiologic survey to determine the prevalence of psychosocial impacts in the populations within a prescribed area around each site. A disproportionate stratified (by distance) random sample of 250 households is surveyed at each site. Data on awareness, knowledge, concern and action regarding the site are also obtained. Scores on pre-validated health measurement scales will be compared with population norms to determine the frequency distribution above, within and below the range of normal. The second stage involves the use of qualitative methodologies to provide an in-depth analysis of the individual, social network and community level factors affecting psychosocial impacts and reactions to the situation. Depth interviews with a sub-sample of survey respondents explore individual perceptions, attitudes and actions. Focus groups composed of members of relevant organizations and discussion groups comprising non-members uncover social network and community perspectives in an interactional setting. Interviews and group sessions are taped and transcribed for content analysis of salient themes. Textual analysis of media reports and other relevant documentation provide insights regarding the informational environment and the community context of the issues.

Adaptation, Psychological

Neurodevelopmental therapy and upper-extremity inhibitive casting for children with cerebral palsy.

The purpose of this research was to study the effect of intensive neurodevelopmental therapy (NDT) and upper-extremity inhibitive casting, separately or in combination, on hand function, quality of upper-extremity movement and range of motion of 73 children with spastic cerebral palsy aged 18 months to eight years. There was no significant difference between intensive or regular therapy and casting or no casting for hand function, between intensive and regular NDT, or between intensive NDT plus casting and the other groups for quality of movement and range of motion. Casting led to increased quality of movement and wrist extension after six months. Casting with NDT improved the quality of upper-extremity movement and range of motion. There appear to be no immediate benefits from intensive therapy alone.

Arm

The role of macrophages in the regulation of primary tumor growth.

Tumor-associated macrophages (TAM) represent a population of tissue macrophages with peculiar biological, biochemical and phenotypic properties. Here we have briefly analyzed two different mechanisms involved in the regulation of the levels of TAM: the production of tumor-derived chemotactic factors for mononuclear phagocytes and in situ proliferation of TAM. Two clones selected from the murine sarcoma line B77 showed a different capacity to produce the tumor-derived chemotactic factor known as JE. Studies with these clones demonstrated a correlation between in vitro production of the protein JE, expression of JE mRNA and macrophage content in tumor tissues, suggesting that the production of chemotactic factors can play a role in the regulation of TAM accumulation. Moreover, it has been shown that TAM had high levels of proliferative activity compared to peritoneal exudate macrophages. In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, the expression of c-fms and macrophage-colony-stimulating factor (M-CSF) was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts, while sarcoma cells had high levels of M-CSF mRNA. Sarcoma-cell-conditioned medium had M-CSF activity on bone marrow cells: this activity was blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M-CSF secreted by sarcoma cells and acting on c-fms-expressing TAM. A better understanding of the regulation and function of TAM may provide a less empirical basis for a rationale design of therapeutic approaches.

Animals

A patient weighted symptom score system in the evaluation of uncomplicated benign prostatic hyperplasia.

A new scoring system is presented for use in patients with uncomplicated benign prostatic hyperplasia. The system is based on the patients' information on the magnitude of twelve symptoms related to bladder and voiding function (symptom score), and three questions related to sexual function. Furthermore the patients are asked to grade the impact of these symptoms on their daily lives (bother score). Multiplication of the two scores related to bladder and voiding function gives the total score. The score related to sexual function is used only for comparing the situation before and after treatment. The new patient weighted total score may assist in creating a solid base for the indication for and evaluation of surgical and non-surgical treatment of uncomplicated benign prostatic hyperplasia.

Humans