Biomedical subjects

S Goldman

Publications and source records attributed to S Goldman.

At least 217 records · Page 12Linked to original sources

PubMed1993

Radiation treatment of epidermoid cancer of the anus.

PURPOSE: The purpose of this study was to evaluate our treatment results of anal cancer. METHODS AND MATERIALS: During the years 1985-1990, 82 patients with invasive epidermoid and cancer were referred to the Department of Oncology at Södersjukhuset. In 76 cases irradiation was used in the primary therapy, and in 43 cases bleomycin was administered concurrently. Fifteen of these tumors were situated in the perianus and 61 in the anal canal. Probability of survival, recurrence, and preservation of anal sphincter was analyzed according to Kaplan-Meier. Cox multivariate analysis was used in studying potential determinants of risk for treatment failure. RESULTS: Tumor-specific survival at 5 years was 71% for both anal canal and perianal cancer. Analyses with regard to cancer of the anal canal indicated that T4 tumors had significantly worse prognosis than those in stages T1-3. Overall survival was 73% and 79% at 5 years for T1 and T2 tumors and 73% and 18% at 4 years for T3 and T4 tumors. Corresponding figures for tumor specific survival were 79%, 79%, 82%, and 31%. Eighty-five percent of patients with T1 tumors, had a preserved anal sphincter after 4 years. For T2 and T3 tumors the corresponding figures were 62% and 60%. Also the multivariate analyses showed stage T4 to be a strong negative prognostic determinant. There was no firm evidence of a positive effect of bleomycin on the treatment results, but it increased the acute radiation toxicity. CONCLUSION: Primary radiotherapy of anal cancer yielded a high probability of survival, but in many cases sphincter amputation have been necessary. The role of bleomycin appears questionable.

Aged↗

PubMed1993

High expression in Escherichia coli of the gene coding for dihydrofolate reductase of the extremely halophilic archaebacterium Haloferax volcanii. Reconstitution of the active enzyme and mutation studies.

The gene coding for the enzyme dihydrofolate reductase of the extremely halophilic archaebacterium Haloferax volcanii was recombined into the Escherichia coli expression vector pET11d. Following induction, the enzyme was produced in large quantities and accumulated in the cells in an insoluble form. The enzymic activity could be efficiently reconstituted by dissolving the aggregate in 6 M guanidine hydrochloride followed by dilution into salt solutions. Mutants were produced in which Lys30 was converted to Leu (K30L), Lys31 was converted to Ala (K31A) and a double mutant in which both lysines were converted (K30L, K31A). The mutated enzymes were produced in E. coli, activated and purified to homogeneity. The effect of the salt concentration on the steady-state kinetic parameters was determined. It was found that the salt concentration affects the Km but not kcat of the various mutants.

Base Sequence↗

PubMed1993

Characterization of a CD34+ cell line established from a child with large cell cutaneous lymphoma.

BACKGROUND: Lymphoma presenting with skin involvement has heterogeneous morphology and rarely is seen in children. To study the pathogenesis of this disease, lymphoma cells from a child with B-cell large cell lymphoma of the skin were cultured in vitro. METHODS: Lymphoma cells cultured on a feeder layer under hypoxic conditions grew in vitro after a latency period of 2 weeks. Since interleukin-6 (IL-6) induces final differentiation of activated B-lymphocytes, the cell line was evaluated for the presence of IL-6 receptors and biologic response to IL-6. RESULTS: An Epstein-Barr virus (EBV)-negative cell line (UoC-B2) was established which expressed CD34, CD45, HLA-DR, CD19, CD20, sIgM, sIgD, and lambda light chain. Good general concordance was observed between the patient's lymphoma and the cell line by comparing the immunophenotype, genotype, and karyotype. The UoC-B2 cells expressed surface IgM but did not secrete IgM into the culture media even in the presence of supplemental IL-6. CONCLUSIONS: A B-lymphoid cell line (UoC-B2) was established from a child with primary cutaneous lymphoma. The cells expressed cell surface IgM and receptors for IL-6 but supplemental IL-6 had no effect on IgM production or cell proliferation.

Antigens, CD↗

PubMed1993

Identification of an ethylene-responsive region in the promoter of a fruit ripening gene.

Transcription of the E4 gene is controlled by an increase in ethylene concentration during tomato fruit ripening. To investigate the molecular basis for ethylene regulation, we have examined the E4 promoter to identify cis elements and trans-acting factors that are involved in E4 gene expression. In transgenic tomato plants a chimeric gene construct containing a 1.4-kilobase E4 promoter fused to a beta-glucuronidase reporter gene is rapidly induced by ethylene in ripening fruit. Deletion of E4 promoter sequences to 193 base pairs reduces the level of GUS activity but does not affect ethylene induction. Transient expression of E4 promoter-luciferase chimeric gene constructs containing various deletions, introduced into tomato fruit pericarp by particle bombardment, indicates that a positive ethylene-responsive region is localized between nucleotides -161 and -85 relative to the transcription start site. DNase I footprint analysis shows that a nuclear factor in unripe fruit interacts specifically with sequences in this element, from -142 to -110, which are required for the ethylene response. The DNase I footprint of this factor is reduced in ethylene-treated unripe fruit and undetectable in ripe fruit. Based on the correlation of a nuclear factor binding site with promoter sequences required for ethylene induction, we propose that this in vitro DNA-binding activity may represent a factor that is involved in ethylene-regulated E4 gene expression.

Base Sequence↗

PubMed1993

A comparison of management patterns after acute myocardial infarction in Canada and the United States. The SAVE investigators.

BACKGROUND: There are major differences in the organization of the health care systems in Canada and the United States. We hypothesized that these differences may be accompanied by differences in patient care. METHODS: To test our hypothesis, we compared the treatment patterns for patients with acute myocardial infarction in 19 Canadian and 93 United States hospitals participating in the Survival and Ventricular Enlargement (SAVE) study, which tested the effectiveness of captopril in this population of patients after a myocardial infarction. RESULTS: In Canada, 51 percent of the patients admitted to a participating coronary care unit had acute myocardial infarctions, as compared with only 35 percent in the United States (P < 0.001). Despite the similar clinical characteristics of the 1573 U.S. patients and 658 Canadian patients participating in the study, coronary arteriography was more commonly performed in the United States than in Canada (in 68 percent vs. 35 percent, P < 0.001), as were revascularization procedures before randomization (31 percent vs. 12 percent, P < 0.001). During an average follow-up of 42 months, these procedures were also performed more commonly in the United States than in Canada. These differences were not associated with any apparent difference in mortality (22 percent in Canada and 23 percent in the United States) or rate of reinfarction (14 percent in Canada and 13 percent in the United States), but there was a higher incidence of activity-limiting angina in Canada than in the United States (33 percent vs. 27 percent, P < 0.007). CONCLUSIONS: The threshold for the admission of patients to a coronary care unit or for the use of invasive diagnostic and therapeutic interventions in the early and late periods after an infarction is higher in Canada than in the United States. This is not associated with any apparent difference in the rate of reinfarction or survival, but is associated with a higher frequency of activity-limiting angina.

Angina Pectoris↗

PubMed1993

Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma.

Certain types of human papillomavirus (HPV) are associated with anogenital carcinomas, including carcinomas of the anal canal. Whereas several serological studies have found an association between papillomavirus antibody responses and cervical carcinoma, the antibody response against papillomavirus antigens among patients with anal carcinoma has not been investigated. The present study has examined the antibody responses to a panel of papillomavirus-derived antigens and compared the serological profile with the histology and HPV carrier state of the tumor, as well as with the stage and prognosis of the disease. Sera from 64 patients with anal cancer and from 79 healthy blood donors were studied in ELISA for the presence of IgA and IgG antibodies to 5 previously described HPV16-derived synthetic peptide antigens. Serum IgA antibodies to a peptide antigen derived from the E2 region of HPV16 were found in 89% of patients with anal cancer as compared to 24% of controls (p = 0.0001). The IgA reactivity to the 4 other antigens showed only low and non-significant increases in mean titer. Serum IgG responses were similar among patients and controls. Among patients who had progressive disease, 21/21 were seropositive for IgA anti-E2 at diagnosis, as compared to 36/43 patients who were in remission after a mean follow-up of 41 months (p = 0.05). Forty-seven cases of anal carcinoma were also studied for the presence of HPV by in situ hybridization using a probe mix of 7 anogenital HPV types. Sixteen patients (35%) carried HPV in their anal cancer and one patient had an HPV-positive benign lesion adjacent to the tumor. Patients with HPV-carrying anal cancer were significantly younger than those with HPV-negative anal cancers (mean age: 57 and 68 years, respectively, p = 0.03). No differences in seroreactivity or HPV carrier state were seen depending on the stage or histological type of the tumor.

Aged↗

PubMed1993

Effects of recombinant human interleukin-11 on hematopoietic reconstitution in transplant mice: acceleration of recovery of peripheral blood neutrophils and platelets.

We have examined the effects of recombinant human interleukin-11 (rhIL-11) on the recovery of peripheral blood cell counts and proliferation of progenitors and hematopoietic stem cells (day 12 colony-forming units-spleen-CFU-S12) in vivo using a mouse bone marrow (BM) and spleen cell transplantation model. Recovery of leukocytes was accelerated in animals receiving daily administration of rhIL-11 (100 micrograms/kg/d) and reached normal levels by day 14 posttransplantation. This increased total leukocyte count reflected mainly an increase in neutrophils. Neutropenia (absolute neutrophil count [ANC] < 1,500) was present in control transplant mice for 14 to 15 days, while in the rhIL-11-treated group, neutrophils recovered to normal by days 8 to 10 and continued to increase until day 19. Animals treated with rhIL-11 had only 1 day with ANC demonstrated < 500. Correspondingly, rhIL-11 treatment increased granulocyte-macrophage progenitors (CFU-GM) derived from both spleen and BM cells. Higher doses of IL-11 increased CFU-GM nearly threefold and CFU-Mix fourfold to fivefold, while increasing burst-forming units-erythroid to a lesser degree. BM and spleen cellularity were both increased in IL-11-treated mice, but no increase in CFU-S12 was noted. In addition, in vivo daily administration of IL-11 increased peripheral platelet counts by threefold over control transplant mice at day 10 posttransplantation during the post-irradiation platelet nadir. Further treatment led to platelet counts higher than normal 18 days posttransplantation when control animals had just attained normal platelet counts. IL-11 can accelerate the recovery of the peripheral blood leukocytes, mainly neutrophils, and platelets in transplant mice, effects that may be clinically useful in future applications for BM transplantation and chemotherapy-related cytopenias.

Animals↗

PubMed1993

Reversible striatal hypermetabolism in a case of Sydenham's chorea.

We studied a 10-year-old girl with Sydenham's chorea (SC) using positron emission tomography (PET) with fluorodeoxyglucose (FDG). Choreic movements involved the head and the left side of her body. PET showed increased glucose metabolism in the right caudate nucleus and putamen. Three months after complete recovery, striatal glucose metabolism had returned to normal in the caudate nucleus. In the right putamen, glucose metabolism had decreased compared to that in the first study but remained elevated compared to that of normal young adults. We propose that the transient striatal hypermetabolism may have been due to increased afferent inputs to the striatum as a consequence of striatal or subthalamic nucleus dysfunction.

Basal Ganglia↗

PubMed1993

Brain glucose metabolism and dopamine D2 receptor analysis in a patient with hemiparkinsonism-hemiatrophy syndrome.

We report findings on brain glucose metabolism and dopamine D2 receptors generated by positron emission tomography (PET) in a 67-year-old woman with right hemiparkinsonism-hemiatrophy syndrome (HP-HA). PET with [18F]-fluorodeoxyglucose (FDG) showed marked glucose metabolism asymmetry. There were significant reductions in glucose uptake at the level of the basal ganglia and, to lesser extent, in the fronto-parietal cortex contralateral to the clinically involved side. These changes were different from those found in a patient with hemi-Parkinson's disease who was scanned under similar conditions. Because the patient with HP-HA had only minimal response to levodopa therapy, we evaluated post-synaptic dopaminergic structures using PET with [18F]-fluoroethylspiperone (FESP). No striatal binding asymmetry was found in FESP/PET, which suggests a sparing of striatal dopamine D2 receptors. The changes in FDG uptake which we found were in brain areas relevant to the clinical features of HP-HA syndrome. In addition, our study provides evidence that FDG/PET may help to differentiate HP-HA syndrome from hemi-Parkinson's disease. In most instances, since HP-HA is associated with a more benign clinical course than Parkinson's disease, this distinction is of clinical important.

Aged↗

PubMed1993

Prognostic significance of serum concentration of squamous cell carcinoma antigen in anal epidermoid carcinoma.

The prognostic significance of pre-treatment serum concentration of squamous cell carcinoma antigen (SCCAg) was investigated in a population of 60 patients with anal epidermoid cancer. Serum concentration was determined during the period 1985-90. The patients were followed until December 1991. An antigen level above 2.0 ng/ml was classified as elevated. Thirty-eight patients had T1-2 tumours, while 22 had T3-4 tumours. Sixteen of the 20 patients (80%) with an elevated SCCAg concentration relapsed or had residual tumour after conclusion of primary therapy, compared to 8 of 40 (20%) with a normal concentration (P = 0.00001). Six patients of 40 (15%) with a normal SCCAg had died at the end of follow-up compared to 10 of 20 (50%) with an elevated value (P = 0.006). For patients with T1-2 tumours 2 of 29 (7%) with a normal SCCAg had died with or from their cancer compared to 3 of 9 (33%) with an elevated value (P = 0.14); for T3-4 tumours these figures were 3 of 11 (P = 0.14); for T3-4 tumours these figures were 3 of 11 (27%) and 7 of 11 (64%) respectively (P = 0.009). Actuarial survival analyses for patients with normal vs elevated SCCAg concentration showed that the projected five year overall survival was 81% for those with a normal level and 43% for those with an elevated level (P = 0.004). For tumour specific survival the figures were 83% vs 45% (P = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

PubMed1993

A modest increase in serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration may influence pregnancy rate and pregnancy loss in in vitro fertilization-embryo transfer (IVF-ET) patients.

PURPOSE: Our purpose was to study the effect of a modest increase in preovulatory serum progesterone (P4) levels in hyperstimulated patients and its association with pregnancy rate and pregnancy loss following in vitro fertilization (IVF) and embryo transfer (ET). PATIENTS: Only patients with mechanical factor and three transferred embryos were included in the present study. They were divided into two groups according to two critical breakpoints for P4 serum levels on the day of hCG administration: serum P4 below 0.6 ng/ml in 28 cycles (group I) and > 0.6 ng/ml in 80 cycles (group II). SETTING: The setting was the IVF program at Carmel Medical Center, Haifa, Israel. RESULTS: The pregnancy rate per embryo transfer was 53% (15/28) in group I and 10% (8/80) in group II (P < 0.025). Of 15 pregnancies achieved in group I, 14 were ongoing pregnancies, compared to 4 of 8 ongoing pregnancies in group II (P < 0.03). CONCLUSIONS: Our findings suggest that a very modest increase in serum P4 levels on the day of hCG administration is associated with lower pregnancy and ongoing pregnancy rates in IVF-ET.

Adult↗

PubMed1993

Studies on the use of thyroid hormone and a thyroid hormone analogue in the treatment of congestive heart failure.

In heart failure, cardiac output is insufficient to meet the needs of the body for oxygen delivery. Available data suggest that alterations in thyroid hormone metabolism may contribute to defective myocardial performance. Accordingly, thyroid hormone or a thyroid hormone analogue that improves cardiac performance might be useful in the treatment of heart failure and has been studied. Experimental and theoretical results of these studies are reviewed and indicate that thyroid hormone increases cardiac output by a combination of effects on the heart and peripheral circulation, specifically by increasing myocardial contractile performance and decreasing venous compliance. In the rat postinfarction model of heart failure, treatment with low doses of thyroxine (1.5 micrograms/100 g) for 3 days produced a positive inotropic response, including an increase in rate of change of left ventricular pressure and a decrease in left ventricular end-diastolic pressure. These changes could be attributed to conversion to triiodothyronine, the active intracellular form of thyroid hormone. When treatment with thyroxine was continued at the same or higher doses (3 to 15 micrograms/100 g) for 10 to 12 days, heart rate increased and improvement in left ventricular end-diastolic pressure was not sustained. More favorable results were obtained with 3,5-diiodothyropropionic acid, a cardiotonic thyroid hormone analogue administered at doses of 375 microgram/100 g, given in combination with captopril. Thus, triiodothyronine or a thyroid hormone analogue may be a useful adjunct to other measures in the treatment of heart failure.

Animals↗

PubMed1993

Triiodothyronine (T3) modulates hCG-regulated progesterone secretion, cAMP accumulation and DNA content in cultured human luteinized granulosa cells.

Ample clinical evidence indicates that women with thyroid disorders frequently exhibit menstrual disturbances and impaired fertility. In order to characterize the nature of thyroid hormone action in the ovary, the direct effects of triiodothyronine (T3) were investigated in vitro using a culture system of human luteinized granulosa cells. The presence of T3 receptors was also searched in such cells. The cell cultures were maintained in serum-free Ham's F-10 medium in the absence or presence of hCG, with or without graded doses of T3 (10(-11)-10(-7) M), and cell proliferation (assessed by DNA content) as well as cell function (cAMP accumulation and progesterone secretion) determined. T3 alone stimulated cell proliferation. hCG, on the other hand, was anti-mitogenic and T3 combined with hCG inhibited cell growth even further, reaching levels below those reached by either control or hCG alone. Exposure of cells to T3 markedly enhanced hCG-induced cAMP accumulation. Addition of 1-methyl-3-isobutylxanthine (MIX) abolished the cAMP-stimulatory effect elicited by T3, suggesting that the thyroid hormone may act, as MIX, by inhibiting phosphodiesterase. T3 was devoid of any influence on basal progesterone secretion, but inhibited hCG-induced secretion of the steroid. The effects of T3 are not accounted for by changes in cell number since the influence of thyroid hormone on cAMP and steroid secretion were expressed per microgram DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Different morphology and proliferative ability of cumulus and granulosa cells originating from cystic follicles aspirated from stimulated in vitro fertilization patients.

OBJECTIVE: To investigate the morphology and proliferative ability of cumulus and granulosa cells (GCs) originating from cystic follicles and normal-sized follicles after ovarian stimulation. DESIGN: Granulosa cells, cumulus cells, and follicular fluid (FF) were aspirated from cystic follicles and normal-sized follicles from the same ovary. Morphology and proliferative ability of cumulus and GCs were assessed by Giemsa stain and thymidine incorporation, respectively. Cell proliferation was assessed in medium or FF originating from cystic follicles or normal-sized follicles. RESULTS: An oocyte was found in 40% of the cystic follicles versus 68% in the normal-sized follicles. Changes in dispersion and adhesion properties were observed in cystic versus normal aspirated corona cumuli complex. Proliferative ability was consistently lower in GCs originating from cystic follicles versus normal-sized follicles. Proliferation of GCs originating from normal-sized follicles or cystic follicles was inhibited or increased when grown in FF from cystic follicles or FF from normal-sized follicles, respectively. Differences in embryo quality were significantly in favor of oocytes originating from normal-sized follicles. Although the fertilization rate of those oocytes appeared to be higher, the difference was not of statistical significance. CONCLUSIONS: Inhibition of GC proliferation in FF from cystic follicles can be reversed by incubating cells in FF from normal-sized follicles. We conclude that factors in the FF may affect cell proliferation.

Cell Division↗

PubMed1993

Functional differentiation in progesterone secretion by granulosa versus cumulus cells in the human preovulatory follicle and the effect of different induction of ovulation protocols.

OBJECTIVE: To investigate P secretion by granulosa cells (GCs) versus cumulus cells derived from human preovulatory follicles. DESIGN: Cells were recovered by aspiration of preovulatory follicles in 44 women participating in an IVF program. Induction of ovulation was performed using clomiphene citrate, hMG and hCG (group I), hMG/hCG (group II), buserelin acetate/hMG/hCG (group III), or Decapeptyl/hMG/hCG (group IV). SETTING: Laboratories of the IVF Unit at the Department of Obstetrics and Gynecology, Carmel Medical Center, Haifa, Israel. MAIN OUTCOME MEASURES: Secretion of P was examined after cultures for 96 hours under nonstimulated and hCG stimulated conditions. RESULTS: Progesterone secretion by GCs derived from all four groups was found to be higher compared with the respective cumulus cells. However, although the ratios of P secretion by GCs versus cumulus cells in groups I, II, and III were very similar, a significantly lower value was observed in group IV. The response of GCs to hCG in terms of P secretion was higher with at least one dose of hCG in groups I and IV compared with groups II and III. The response of cumulus cells to hCG was absent regardless of the treatment protocol used in vivo. CONCLUSION: Our results demonstrate that in the human preovulatory follicle, GCs and cumulus cells differ in their capacity to secrete P as well as in their response to hCG. They further suggest that the mode of induction of ovulation affects the relative capacity of GCs and cumulus cells to secrete P and their ability to respond to hCG.

Adult↗

PubMed1993

Benign retroperitoneal fibrosis and renal cell carcinoma.

We report benign retroperitoneal fibrosis associated with renal cell carcinoma in a 56-year-old woman. Based on the preoperative evaluation and initial surgical exploration, the retroperitoneal mass was assumed to be metastatic renal cell carcinoma and chemotherapy rather than surgical resection was offered to the patient. A second opinion was sought and repeat exploration revealed a resectable cell carcinoma and retroperitoneal tissue that was pathologically benign idiopathic retroperitoneal fibrosis. This report emphasizes that a patient with an otherwise resectable primary tumor must undergo multiple, deep biopsies of retroperitoneal masses before making a presumptive diagnosis of malignant retroperitoneal fibrosis secondary to metastatic cancer.

Biopsy↗

PubMed1993

Posttraumatic cervical dystonia.

Posttraumatic cervical dystonia has been described as a distinct syndrome with some similarities to idiopathic nontraumatic cervical dystonia (torticollis). We describe five patients in whom cervical dystonia developed immediately after relatively mild trauma to the neck. Four of the five patients had persistent contractions of all cervical muscles including the trapezius muscles, which almost completely prevented motion of the neck and resulted in muscle hypertrophy. The condition persisted unabated in all patients for the entire period of follow-up (duration, 1 1/2 to 3 years). Pharmaceutical interventions, which had been used previously for idiopathic nontraumatic cervical dystonia, failed to benefit these patients. Two patients who received injections of botulinum toxin had no more than mild benefit. Selective denervation was inapplicable because of the widespread involvement of all cervical muscles in all but one patient. Physical therapy was essentially ineffective. Because of the unusual features and possible medicolegal setting, clinicians may tend to diagnose this condition as a psychogenic disorder or litigation-oriented behavior. The clinical picture, however, is consistent with an organic dystonia that may render the patient functionally and occupationally disabled.

Accidents, Traffic↗

PubMed1993

Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin-releasing hormone agonist and outcome of in-vitro fertilization.

The present study was undertaken to assess whether the increase in serum progesterone concentration following the administration of human chorionic gonadotrophin (HCG) may have predictive value on the in-vitro fertilization (IVF) success rate. Progesterone concentration on the day of HCG administration and the increase in progesterone concentration on the following day were evaluated in 140 consecutive patients undergoing IVF with embryo transfer. Stimulation protocol in all study patients entailed intranasal administration of short-acting gonadotrophin-releasing hormone agonist (GnRHa) buserelin and human menopausal gonadotrophin. A pregnancy rate of 37.2% was achieved when at least three embryos were transferred. The only significant difference between conception and non-conception cycles was found in serum progesterone concentrations after HCG administration (P < 0.01), whereas the mean progesterone concentration on the day of HCG did not differ. No difference in other hormonal or cycle parameters was observed. The increase in progesterone concentration was significantly greater in the group of patients who achieved pregnancy than in the group who did not (2.2 +/- 0.2 versus 1.6 +/- 0.1 ng/ml, respectively; P < 0.01). A critical breakpoint in serum progesterone was arbitrarily determined at 1 ng/ml. An increase in progesterone concentration > or = 1 ng/ml when three or more embryos were transferred was associated with a positive predictive value for pregnancy of 40.4% (sensitivity of 94.7%), whereas a negative predictive value of 86.7% was obtained when this value was < 1 ng/ml. These findings indicate that an adequate rise in serum progesterone following HCG administration provides useful information about the possible outcome of the treated cycle.

Adult↗