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Biomedical subjects

M Wick

Publications and source records attributed to M Wick.

13 recordsLinked to original sources
PubMed1992

Percutaneous ureteral occlusion with use of Gianturco coils and gelatin sponge. Part I. Swine model.

An animal model was developed to study ureteral occlusion produced by steel coils and gelatin sponge. A coil nest was formed in the ureter, and in all but one pig, gelatin sponge pledgets were incorporated in the coil nest. Animals were killed at 2 hours, 1 week, 1 month, and 2 months. High-grade obstruction was present immediately following the procedure in all animals and was documented to be persistent by means of antegrade nephrostograms obtained just prior to death. At gross examination after death, ureteral thickening and strictures were evident. Histologic studies helped confirm the presence of acute and chronic inflammatory changes. In the in vivo model, gelatin sponge was not found necessary for acute ureteral occlusion. However, in an ancillary in vitro study in which a rigid plastic tube was used, gelatin sponge was necessary in addition to coil occlusion to provide acute total obstruction. The authors' findings suggest that in a compliant ureter, coil occlusion alone produces sufficient mechanical occlusion. Long-term obstruction is probably due to mechanical obstruction and stricture formation.

Animals↗
PubMed1992

Inhibition of Fos- and Ras-induced transformation by mutant Fos proteins with structural alterations in functionally different domains.

We show that transformation-defective Fos proteins lacking either a functional leucine zipper (mutants L345 and J/R510s) or the 110 amino-terminal amino acids (mutant BR800) inhibit the induction of morphological transformation by v-Fos. Both types of mutants specifically repress transformation without any significant effect on cell proliferation. In contrast, several transformation-defective Fos mutants with structural alterations in the acidic region or the right half of the adjacent basic DNA contact site do not show any inhibition of transformation. This result, taken together with the repression of transformation by the leucine zipper-deficient mutants L345 and J/R510s, indicates that the interaction of Fos with proteins other than Jun is necessary for transformation. The leucine zipper-deficient mutants also inhibit Fos-mediated activation of AP-1-dependent transcription. This suggests that their inhibitory effect on transformation may at least in part be the result of the squelching of proteins other than Jun family members that are required for Fos-mediated transactivation. All three mutants were also found to inhibit transformation by the point-mutated H-ras oncogene from EJ carcinoma cells and to trigger a partial reversion of the transformed phenotype of Ras-transformed fibroblasts. These findings support the conclusion that Ras-induced transformation involves signal transduction pathways inducing the c-fos gene.

Cell Division↗
PubMed1991

Identification and partial characterization of angiogenesis bioactivity in the lower respiratory tract after acute lung injury.

Survival after acute lung injury (ALI) depends on prompt alveolar repair, a process frequently subverted by the development of granulation tissue within the alveolar airspace. Immunohistochemical examination of the intraalveolar granulation tissue confirmed that capillaries as well as myofibroblasts were the principal cellular constituents. We therefore hypothesized that angiogenesis factors would be present on the air-lung interface after ALI. To evaluate this hypothesis, bronchoalveolar lavage fluid from patients with ALI (n = 25) and patient controls (n = 8) was examined for angiogenesis bioactivity by its ability of induce endothelial cell migration. While lavage fluid from controls had no bioactivity, lavage fluid from 72% of patients with ALI promoted endothelial cell migration. Heparin affinity, ion exchange, and gel filtration chromatography resolved the bioactivity into at least two moieties. One appeared identical to the well characterized endothelial cell growth factor, basic fibroblast growth factor. The other was a 150-kD non-heparin binding protein that mediated endothelial cell migration and attachment in vitro, and the growth of new vessels in vivo. These data are consistent with the hypothesis that the growth of capillaries into the alveolar airspace results from angiogenesis factors present on the alveolar surface of the lung after ALI.

Acute Disease↗
PubMed1991

Myasthenia gravis: measurement of anti-AChR autoantibodies using cell line TE671.

Anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis (MG) can be quantitated using AChR extracted from the human rhabdomyosarcoma cell line TE671 (AChRTE671) as a practical alternative to AChR from human amputated limbs (AChRAMP). We compared the two antigen preparations using serum samples from different clinical groups of MG patients (n = 112) and various controls (n = 189). With two exceptions, both tests were positive or negative in the same patients. However, in the generalized MG group, the TE671 assay yielded significantly lower titers than the AChRAMP assay.

Adolescent↗
PubMed1990

A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma.

Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 X 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks. Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades III or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.

Adult↗
PubMed1990

In vivo radioprotective effects of recombinant human granulocyte colony-stimulating factor in lethally irradiated mice.

The purpose of this study was to investigate the in vivo radioprotective effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the effects of increasing doses of rhG-CSF on survival of mice receiving 700 cGy (LD100/30) single dose total body irradiation (TBI). While 1 microgram/kg to 100 micrograms/kg doses of rhG-CSF were not radioprotective, a dose-dependent radioprotection was observed at 200 micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four different rhG-CSF treatment regimens side by side for their radioprotective effects in LD100/30 irradiated mice. One hundred percent of control mice receiving phosphate buffered saline died within 21 days after TBI with a median survival of 14 days. The median survival was prolonged to 20 days and the actuarial 60-day survival rate was increased to 27% when mice received 2,000 micrograms/kg rhG-CSF 24 hours before TBI (P = .0002; Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24 days and the actuarial 60-day survival rate was increased to 33%, when mice were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was administered in two divided doses of 1,000 micrograms/kg given 24 hours before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen prolonged the median survival time of LD100/30 irradiated mice to more than 60 days and increased the actuarial 60-day survival rate to 62% (P = .0001; Mantel-Peto-Cox). By comparison, no survival advantage was observed when mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects were observed when mice were irradiated with 650 cGy (LD80/30). The presented findings provide conclusive evidence that rhG-CSF has significant in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.

Animals↗
PubMed1989

Myelin basic protein in the cerebrospinal fluid of patients infected with HIV.

The major pathological abnormalities of HIV encephalopathy are infiltrates of macrophages, multinucleated giant cells, microglial nodules and demyelination. Elevated myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) provide a marker for central nervous system demyelination. The purpose of this study was to investigate the possible role of CSF MBP as a useful and early marker for HIV encephalopathy. The CSF of 40 consecutive patients with HIV infection of various clinical stages was investigated, including 13 patients with clinical signs of HIV encephalopathy. CSF MBP was elevated in 2 patients (5.0 and 5.3 ng/ml), both of whom had moderate to severe HIV encephalopathy. The course of the disease was rapid in both patients. In the remaining 38 patients, CSF MBP levels were marginally elevated (n = 12) or normal (n = 26). Our results suggest that CSF MBP is not a sensitive marker for the diagnosis and evaluation of HIV encephalopathy, but may be an indicator of prognosis for the course of the disease. There were only few findings of elevated CSF MBP levels in patients with HIV encephalopathy in the current study, and this may be because the disorder progressed slowly in most patients. It is possible that CSF MBP levels in HIV encephalopathy may only be elevated with acute clinical deterioration but are normal in slowly progressive forms of demyelination, as seen in multiple sclerosis.

AIDS-Related Complex↗
PubMed1989

Testicular germ cell loss in children with renal failure.

Delayed puberty, hypergonadotropism, impaired spermatogenesis, decreased libido and infertility have been reported in males with chronic renal failure (CRF). The number of spermatogonia per seminiferous tubule was quantitated in 22 children with renal failure (RF) in this study using anti-neuron-specific enolase to selectively label these cells. Results were compared to those of puberty and age-matched controls and were subjected to statistical analysis. This study showed that: 1) Children and adolescents with RF have a significantly decreased number of spermatogonia per seminiferous tubule, compared to puberty and age-matched controls; 2) Germinal cell counts in infants with RF under 3 months of age compared to control infants do not reach statistical significance but are borderline; 3) Children with RF over 3 months of age have statistically fewer germinal cells than age-matched controls, a difference which appears to increase with age; 4) Not all children with RF have decreased numbers of spermatogonia while some have an absence of these cells; and 5) The number of spermatogonia per tubule is correlated with increasing age but is not correlated with the duration of RF.

Autopsy↗
PubMed1988

Hypercortisolism due to an autonomously functioning pituitary adenoma: limitations in diagnostic test procedures.

We report a patient with pituitary-dependent Cushing's syndrome in whom standard biochemical testing procedures failed to define the pituitary as the source of autonomous hormone secretion. Anomalous findings included: 1) wide variations of urinary steroid excretion during a 4-day dexamethasone suppression test, 2) a rise of the serum cortisol after the single dose (8 mg) overnight dexamethasone suppression test, 3) a diminished serum 11-deoxycortisol response to the metyrapone test, and 4) an absent plasma ACTH response to CRH. While the results of these studies were most consistent with an ectopic source of ACTH production, magnetic resonance imaging suggested that Cushing's syndrome was due to a pituitary adenoma. The adenoma was removed by transphenoidal surgery. However, serum and urinary steroid levels remained measurable for 2 weeks because of the perioperative use of im cortisone acetate. Subsequent im administration of 200 mg cortisone acetate again led to prolonged serum and urinary steroid responses to this compound, thus emphasizing the pitfalls that may accompany the perioperative use of cortisone acetate. This patient demonstrates the importance of performing multiple tests, including magnetic resonance image scanning, in evaluation Cushing's syndrome, since standard biochemical testing may not indicate pituitary ACTH hypersecretion as the cause.

Adenoma↗