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Biomedical subjects

A Adler

Publications and source records attributed to A Adler.

At least 73 records · Page 4Linked to original sources
PubMed1997

Characterization of soluble gp130 released by melanoma cell lines: A polyvalent antagonist of cytokines from the interleukin 6 family.

gp130 acts as a common transducing signal chain for all receptors belonging to the interleukin (IL)-6 receptor family. The IL-6-related cytokines [IL-6, IL-11, oncostatin M (OSM), leukemia inhibitory factor, ciliary neurotrophic factor, and cardiotrophin] often modulate tumor phenotype and control the proliferation of many tumor cell lines. We demonstrate that melanoma cell lines release, in vitro and in vivo (when transplanted in nude mice), soluble gp130 (sgp130), a potential antagonist of cytokines from the IL-6 family. Biochemical analysis revealed that sgp130 derived from melanoma patients' sera or from culture supernatants of melanoma cell lines is a Mr 104,000 protein that resolved after deglycosylation as a Mr 58,000 protein. PCR and Northern blot analysis only identified one gp130 membrane mRNA, suggesting that the soluble form of gp130 is generated by proteolytic cleavage. OSM reproducibly increases sgp130 released by melanoma cell lines, whereas leukemia inhibitory factor stimulates the production of sgp130 in only one of three cell lines tested. This tumor-derived sgp130 is functional because it binds in solution to the IL-6-soluble IL-6 receptor (gp80) complex. Recombinant sgp130 inhibits the growth inhibitory activity of the IL-6-soluble IL-6 receptor complex and OSM on some melanoma cell lines. Therefore, this soluble gp130 represents a natural antagonist of cytokines from the IL-6 family.

Animals↗
PubMed1996

A model for the incorporation of intracytoplasmic sperm injection into a private practice in vitro fertilization program.

OBJECTIVE: To describe a method for the training of personnel and the implementation of intracytoplasmic sperm injection (ICSI) into an IVF program. The results of the first 75 cycles are reviewed. DESIGN: Retrospective review of the first 75 consecutive ICSI procedures. SETTING: Private, community-based IVF program. MAIN OUTCOME MEASURES: The fertilization rate, damage rate, ongoing pregnancy rate (PR), and implantation rate were measured. RESULTS: Nine percent of the injected oocytes were damaged. The fertilization rate was 60%, and the cleavage rate was 98%. Fifty-nine percent of the cycles resulted in an ongoing pregnancy, and the implantation rate per embryo was 26%. CONCLUSIONS: A high initial PR can be obtained with ICSI using a systematic training regimen.

Adult↗
PubMed1996

[High-resolution magnetic resonance tomography by means of an endorectal coil--the results in rectal tumors].

PURPOSE: To assess the value of high-resolution MRI of the rectum using an endorectal coil. METHODS: 10 volunteers and in 31 patients with suspected rectal tumors were examined. In 17 patients (n = 17) with rectal carcinoma, of which 15 subsequently underwent radical surgery, the preoperatively obtained tumor stage was compared with histology. In 12 patients (n = 12) with rectal adenoma (severe and medium graded epithelial dysplasias according to the WHO) who underwent endoscopy the results of the endorectal surface coil examination were compared with endoscopy and histology. In 4 patients (n = 4) with large rectal adenomas the surface coil was used before and as follow-up after endoscopic electro laser resection and the absence of adenoma after therapy also in the deeper layers of the rectal wall could be confirmed. RESULTS: Visualization of anatomical structures of rectum and adjacent structures is improved by the use of the endorectal surface coil. The diagnosis of carcinoma and adenoma of the rectum and the documentation of the exact extension can be reached with high accuracy (85%). CONCLUSION: MRI with an endorectal surface coil may play an important role in the preoperative diagnosis of rectal carcinoma. This method is useful for primary diagnosis and follow-up of large rectal adenoma after endoscopic electro laser resection.

Adenoma↗
PubMed1996

Impedance imaging of lung ventilation: do we need to account for chest expansion?

Electrical impedance tomography (EIT) uses surface electrical measurements to image changes in the conductivity distribution within a medium. When used to measure lung ventilation, however, measurements depend both on conductivity changes in the thorax and on rib cage movement. Given that currently available reconstruction techniques assume that only conductivity changes are present, certain errors are introduced. A finite element model (FEM) is used to calculate the effect of chest expansion on the reconstructed conductivity images. Results indicate that thorax expansion accounts for up to 20% of the reconstructed image amplitude and introduces an artifact in the center of the image tending to "move" the reconstructed lungs closer together. Although this contribution varies depending on anatomical factors, it is relatively independent of inspiration depth. For certain applications in which one is only interested in changes in the level of physiological activity, the effect of the expansion can be neglected because it varies linearly with impedance changes. We conclude that chest expansion can contribute significantly to the conductivity images of lung ventilation and should be taken into account in the interpretation of these images.

Algorithms↗
PubMed1996

Hypertension and diabetes among Siberian Yupik Eskimos of St. Lawrence Island, Alaska.

CHANGING DIETS AND LIFESTYLES contribute to an increase in the prevalence of cardiovascular disease and diabetes in Alaska Natives. To examine the problem in detail, we have begun a systematic screening of various ethnic groups by carrying out a pilot study of Siberian Yupik Eskimos ages 39 and over. Mean LDL and HDL levels were 157 mg/dl and 63 mg/dl. Mean fasting insulin was 7.0 microunits/ml; and mean BMI, 27.1. Fasting insulin level was significantly related to both diastolic blood pressure and fasting triglyceride levels, but not to systolic blood pressure, total cholesterol, LDL cholesterol, or HDL cholesterol levels. Of the 66 people screened, 27% had evidence of hypertension.

Adult↗
PubMed1995

Relationship between an index of tidal flow and lower respiratory illness in the first year of life.

The ratio of time to tidal peak flow (Tme) to total tidal expiratory time (Te) has been reported to be decreased in infants who later develop wheezing lower respiratory tract illness (LRI) in the first year of life. The relationship between Tme/Te to the subsequent occurrence of LRI was studied in 98 infants in whom the first measurement of pulmonary function (PFT) was made before the age of 6 months and before the occurrence of any LRI. Occurrence of LRI was evaluated by standardized questionnaires at well-baby visits, through biweekly telephone calls to mothers, and review of all visits to physicians. Tme/Te was derived from 10 tidal breathing loops during stable respiration. Partial expiratory flow-volume curves were obtained with the rapid compression technique, and passive respiratory mechanics were evaluated by the single breath occlusion technique. Analysis of Tme/Te was stratified by age (< or = 10 weeks, > 10 weeks to 6 months) to take into account the age-related decline in Tme/Te. Among 80 infants first tested at < or = 10 weeks, Tme/Te was 12.4% shorter in those who developed a LRI vs. those who did not (P = 0.46); for 18 infants tested after 10 weeks, the difference was 1.9% (P = 0.39). Among male infants, the decrease in Tme/Te was observed only for those studied at < or = 10 weeks (16%, P = 0.16). For females, decreases were observed for those tested at < or = 10 weeks (11%, P = 0.83) and those tested after 10 weeks (17.5%, P = 0.09). Poisson regression analysis which included data for multiple measurements of Tme/Te over the first year of life and adjusted for age-at-test and maternal smoking during pregnancy also demonstrated a greater decrease in Tme/Te in female infants who subsequently develop an LRI (P = 0.08). Level of Tme/Te was not consistently related to level of respiratory system resistance (RRS) or flow at functional residual capacity (VFRC). Level of VFRC has been shown previously to be related to the occurrence of LRI and in this study to RRS(P = 0.007). The results indicate (1) a shortened Tme/Te is only weakly associated with the development of LRI in the first year of life; (2) this ratio is a less precise and an epidemiologically less useful measure than is VFRC to investigate groups of infants with and without LRI and without clinically significant underlying lung disease.

Age Factors↗
PubMed1995

Intracytoplasmic sperm injection: a novel treatment for all forms of male factor infertility.

OBJECTIVE: To demonstrate the effectiveness of intracytoplasmic sperm injection to treat male factor infertility and to report on the achievement of fertilization and pregnancy compared with standard in vitro insemination. DESIGN: Controlled clinical study. SETTING: Couples suffering from male factor infertility treated in an academic research environment. PATIENTS: Two hundred twenty-seven couples in whom the male partners were presumed to be the cause of repeated failed attempts at IVF or whose semen parameters were unacceptable for conventional IVF. INTERVENTIONS: Oocytes for this study were harvested after superovulation with GnRH agonist and gonadotropins. After removing the cumulus cells, a single spermatozoon was injected directly into the cytoplasm of metaphase II oocytes, and the outcome was analyzed in terms of semen parameters and origin of semen sample. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates (PRs) in relation to sperm parameters and origin of semen sample. RESULTS: Two hundred twenty-seven couples were treated by intracytoplasmic sperm injection resulting in an ongoing pregnancy rate of 37.0% per retrieval (84/227). There were 47 singleton pregnancies (5 of which were vanishing twin pregnancies), 30 twin gestations, 6 triplet pregnancies, and 1 quadruplet pregnancy. The concentration of the total motile spermatozoa present in the ejaculate as well as the origin of the samples influenced the fertilization rate but not the pregnancy outcome. CONCLUSIONS: Intracytoplasmic sperm injection can be used successfully to treat couples who have failed IVF or who have too few spermatozoa for conventional methods of in vitro insemination. Sperm parameters do not clearly affect the outcome of this technique.

Adult↗
PubMed1995

Cystic fibrosis gene mutations do not affect sperm function during in vitro fertilization with micromanipulation for men with bilateral congenital absence of vas deferens.

OBJECTIVE: To assess the effects of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations on sperm function and fertility in men with bilateral congenital absence of the vas deferens. DESIGN: Prospective. SETTING: Division of urologic microsurgery and associated hospital-based IVF unit. MAIN OUTCOME MEASURES: Fertilization and pregnancy rates. PATIENTS: Men referred to our fertility unit for treatment of bilateral congenital absence of the vas deferens, using sperm surgically retrieved from the epididymis with IVF and micromanipulation. RESULTS: Of 45 men with bilateral congenital absence of the vas, 54% (19/35) tested were found to be carriers of CFTR gene mutations, with one compound heterozygote. Epididymal sperm from men affected with CFTR mutations fertilized 19% (29/152) of oocytes, whereas men without mutations fertilized 22% (44/204) of oocytes. Pregnancy rates (PRs) were 36% (5/14) for cycles involving men with CFTR mutations and 33% (5/15) for other patients with congenital absence of the vas deferens but without detectable CFTR mutations. CONCLUSIONS: The presence of detectable CFTR mutations does not affect fertilization rates or PRs for men with bilateral congenital absence of the vas deferens when IVF and micromanipulation are applied.

Cystic Fibrosis↗
PubMed1995

Micropuncture retrieval of epididymal sperm with in vitro fertilization: importance of in vitro micromanipulation techniques.

OBJECTIVES: To evaluate the importance of in vitro micromanipulation techniques, specifically intracytoplasmic sperm injection (ICSI), for the fertility treatment of men with congenital absence of the vas deferens (CAV) or other unreconstructable male reproductive tract obstruction. METHODS: Results using ICSI during in vitro fertilization (IVF) were compared to previously published results of IVF alone and IVF with other micromanipulation techniques at the same infertility center. Main outcome parameters evaluated were: fertilization rate per oocyte, clinical pregnancy rate, and ongoing pregnancies and deliveries. RESULTS: IVF with ICSI yielded a fertilization rate per oocyte of 140 of 312 (45%) and a clinical pregnancy rate of 14 of 27 (52%) per cycle of sperm and egg retrieval. Ongoing pregnancies or deliveries have occurred for 13 of 27 (48%) cycles with ICSI. These results were better than our previously published results of IVF alone or in conjunction with the micromanipulation techniques of subzonal insertion (SuZI) or partial zona dissection (PZD) that yielded a 119 of 631 (19%; P < 0.0001) fertilization rate, clinical pregnancy rate of 14 of 51 (27%; P < 0.001) and ongoing pregnancy or delivery for 12 of 51 cycles (24%; P < 0.001). CONCLUSIONS: Epididymal sperm retrieval should be performed only when micromanipulation is available in conjunction with IVF to maximize chances of fertilization and subsequent pregnancies. The use of ICSI for epididymal sperm appears to maximize chances of pregnancy for couples with surgically unreconstructable obstructive male infertility.

Cytoplasm↗
PubMed1995

Intracytoplasmic sperm injection in dysmorphic human oocytes.

Fertilisation and development of dysmorphic human oocytes recovered from hyperstimulated ovaries have been evaluated following intracytoplasmic sperm injection (ICSI) for treatment of male infertility. A total of 2968 oocytes at metaphase II of meiosis were injected, of which 806 (27.2%) were dysmorphic at the light microscopic level. Cytoplasmic abnormalities included granularity, areas of necrosis, organelle clustering, vacuoles, and accumulating saccules of smooth endoplasmic reticulum. Anomalies of the first polar body and zona pellucida, as well as non-spherical shapes of oocytes, were also noted. Contrary to previous findings linking some dysmorphisms to non-assisted fertilisation failure, in this study no single abnormality led to a reduction in the fertilisation rate, nor was fertilisation compromised in oocytes with multiple abnormalities. The incidence of normal fertilisation (two pronuclei and two polar bodies) was 69% in both the dysmorphic and non-dysmorphic oocytes. While overall pregnancy and implantation results were not altered in the group of patients (n = 242) in whom at least one dysmorphic oocyte was injected, exclusive replacement of embryos which originated from dysmorphic oocytes led to a higher incidence of early pregnancy loss. It is concluded that aberrations in the morphology of human oocytes--most probably a product of controlled ovarian stimulation--are of little or no consequence to fertilisation or early cleavage after ICSI. It is possible, however, that these embryos have a reduced potential for implantation and further development.

Embryo Implantation↗
PubMed1995

Endoscopic resection of large colorectal adenomas: a combination of snare and laser ablation.

BACKGROUND AND STUDY AIMS: Endoscopic resection of large colorectal adenomas is still not a standard procedure, treatment with a high diathermic snare is considered as difficult and risky, and the main disadvantage of laser vaporization is the unavailability of histological evaluation. We studied a combined technique that enjoys the benefits of both techniques and avoids the disadvantages and risks of each. PATIENTS AND METHODS: In a prospective study, we combined the techniques of high-frequency snare resection as a preparatory method and Nd: YAG laser vaporisation as a second-stage treatment. In 72 patients, we resected 79 adenomas, most of them in the rectum (81.0%) and with a tubulovillous histology (69.6%), with a mean volume of 9.4 cm3 (1.5-29.0 cm3) and a base diameter ranging from 20 mm to 80 mm. RESULTS: After using the combined technique of preparatory mucosectomy as a first step and laser vaporization as the second step, follow-up evaluation was possible in 50 out of 72 patients (69.4%). Fourteen patients had a local relapse of adenoma (28.0%), with dysplasia histologically of the same grade or a lower one compared to the original grade, after a mean of 1.4 years. Since these local recurrences were diagnosed at a size of a few millimeters (less than 3 mm), a further session of laser treatment eliminated the material completely without complications. No colorectal carcinomas were observed. CONCLUSIONS: The high clinical long-term success of our combined electro-laser resection is not only a result of complete endoscopic adenoma resection, but also of a strong control regimen. This technique is applicable to the treatment of large colorectal adenomas with curative intent.

Adenoma↗
PubMed1995

Development and implementation of intracytoplasmic sperm injection (ICSI).

The purpose of this paper is to elucidate the experimental steps that led to the development of intracytoplasmic sperm injection (ICSI) and its application in the human. ICSI has become the most successful micromanipulation procedure for treating male infertility. A total of 355 in vitro fertilization (IVF) cycles utilizing ICSI are described; 180 couples were previously treated in 509 IVF cycles but achieved no fertilization and 175 couples could not be treated by IVF because of extremely poor semen parameters. Of the 3063 metaphase II (M II) oocytes retrieved, 2970 were injected with a survival rate of 93.6%, yielding 1917 bipronuclear zygotes (64.5%). In 148 patients, a foetal heart was evidenced by ultrasound; 11 of these patients miscarried between 7 and 13 weeks of gestation. The ongoing pregnancy rate was 38.6% (137/355) per retrieval and 40.5% (137/338) per embryo replacement. At the time of writing, there were 22 deliveries and one therapeutic abortion for a trisomy 21 chromosomal abnormality. In addition, 66 singleton, 37 twin, 10 triplet and 1 quadruplet pregnancies were ongoing. The concentration of motile spermatozoa in the ejaculate only slightly influenced the fertilization rate (P < 0.001) and the pregnancy outcome (P < 0.01). A preliminary injection procedure utilizing intracytoplasmic injection of isolated sperm heads was performed in 35 M II human oocytes with resultant fertilization and cleavage rates of 74% and 73% respectively. Skills in ICSI were acquired by injecting hamster and unfertilized human oocytes with human sperm. ICSI can be used to successfully treat couples who have failed IVF or who have too few spermatozoa for conventional in vitro insemination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

In vitro cell-mediated immune responses induced by a polyvalent allogeneic melanoma vaccine.

Peripheral mononuclear cells (PMNC) from 18 melanoma were monitored for vaccine-related changes in their immune responses by measuring functional activity and phenotypic expression of PMNC prior to- and following 4-6 vaccinations. Assays included: cytolytic responses directed against melanoma cell lines included in the vaccine (M20, M14, HM54 and SKMel28), control melanoma (SKMel23) and non-melanoma (SKCo1, K562 and Daudi) cell lines. Direct lytic responses were significantly enhanced following vaccine treatment, mainly against M20 cell line and was further augmented following In Vitro Stimulation (IVS) by Mit-C-treated M20 or M14 cells. No evidence was found of augmentation of NK or LAK activity by vaccine treatment. Significantly enhanced proliferative responses to of vaccine-treated patients' PMNC to melanoma cell lines were also observed. The human melanoma cell lines used for vaccine preparation (M14, M20 and SKMel28) are high expressors of HLA class I, while high expression of HLA-DR only on M20 cells. Cell surface markers' study indicate a shift in CD4/CD8 ratio from 1.1 to 2.1 and increase in CD25 and HLA-DR positive cells. In M20-stimulated cultures of post-vaccine patients' PMNC the predominant phenotype was CD3+/CD4+. In conclusion, we have demonstrated that treatment with polyvalent allogeneic melanoma vaccine significantly augments T-cell mediated CD3+/CD4+), anti-melanoma lytic and proliferative responses, non-MHC-restricted.

Adult↗
PubMed1995

Allogeneic human liposomal melanoma vaccine with or without IL-2 in metastatic melanoma patients: clinical and immunobiological effects.

The aim of this pilot study was to assess the clinical and immunological effects of human allogeneic liposomal melanoma vaccine alone or combined with Interleukin-2 (IL-2) in patients with metastatic melanoma. Four concurrent treatment arms were included: vaccine alone (A); vaccine combined with systemic IL-2 (B); vaccine combined with low-dose liposomal regional IL-2 (C); and low-dose regional IL-2 as in group C but without vaccine (D). Vaccine was prepared from semisynthetic phospholipids (dimyristol phosphatidylcholine and dimyristol phosphatidylglycerol) and membranes of six human melanoma cell lines. The latter were chosen as expressing MHC class I and II antigens and a "mosaic" of melanoma-associated antigens (MAAs) as detected by MoAbs R24, p97, CF21 and TA99. Nine of the 24 patients had objective clinical responses: of the ten patients treated with liposomal vaccine and low dose regional IL-2 (arm C), three had complete responses (CR) and three had partial responses (PR); of the five patients treated with liposomal, low-dose regional liposomal IL-2 only (arm D), three had PRs. No clinical responses were seen in patients treated by vaccine alone (A) nor in patients treated by vaccine and systemic IL-2 (B). Patients' in vivo and in vitro cellular immune responses were closely monitored. Conversion to positive cutaneous delayed type hypersensitivity (DTH) to membrane vaccine (without liposomes) was induced only in the six clinical responders of arm C. Positive DTH correlated with augmented in vitro proliferative lymphocyte responses stimulated by melanoma cell lines and membrane preparation and with the augmented cytolytic activity against melanoma cell lines.

Adult↗
PubMed1995

[Comparative imaging of HIV associated diseases of the hepatobiliary system in computerized tomography and cholangiography].

With the incidence of AIDS being on the rise, diagnostic work-up of hepatobiliary disease in these patients is of increasing interest. 57 x-ray cholangiograms and computed tomographic studies of 13 AIDS-patients with clinical signs of cholangitis were reviewed. Nine patients had abnormal cholangiographic findings. Computed tomography of 8 patients revealed hepatobiliary disease in six cases. Of three patients with cholangiograms reflecting bile duct dilatation of neoplastic aetiology, CT was required in two for definite diagnosis. Cholangiography is the method of choice for diagnosing AIDS-associated cholangitis, whereas computed tomography compares favourably in depicting neoplastic disease of the hepatobiliary system. Follow-up of AIDS-associated cholangitis usually delineates unchanged radiologic findings.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Radioisomorphisms of sclerosing cholangitis].

For differentiation of Primary Sclerosing Cholangitis (PSC) from AIDS-associated cholangitis (AAC), 95 CT or Cholangiography studies of 37 patients were reviewed and signs of biliary disease analysed. Only two each of PSC and AIDS-subjects were free from biliary lesions compatible with some kind of sclerosing cholangitis. Subgroup analysis revealed wide overlapping of morphological findings in PSC and AAC. We conclude that radioisomorphism of etiologically different forms of sclerosing cholangitis may indicate pathophysiologically similar courses.

AIDS-Related Opportunistic Infections↗