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Biomedical subjects

S C Jacobs

Publications and source records attributed to S C Jacobs.

At least 73 records · Page 4Linked to original sources
PubMed1995

Satellite cell activation after muscle damage in young and adult rats.

BACKGROUND: Level exercise leads to focal structural damage in muscle fibers and to an increase of creatine kinase in the blood. We questioned whether it also induces activation of young and adult muscle satellite cells toward proliferation. METHODS: Rats of two different ages, 6 and 16 weeks, were forced to run on a level treadmill and killed at different time intervals. The temporal profile, up to 3 weeks, of muscle damage was investigated by quantification of the focally disturbed fiber area in longitudinal sections of the m. soleus. Bromodeoxyuridine (BrdU) was injected before death to determine the labeling index of satellite cells. Labeled and unlabeled satellite cells, myonuclei, and fibers were counted in cross sections of the belly part of the muscles. RESULTS: The muscle fiber damage differed in both amount and temporal profile between young and older animals. Damage was already visible immediately after running. However, whereas in the younger animal the amount of damage increased gradually in time until 8% at 48 hours and disappeared to almost control levels at 1 week after running, in the older animals the amount of damage was lower but remained present for at least 2 weeks. The cell kinetic data on both groups showed a proliferation response of satellite cells throughout the muscle. The effects were most pronounced in the older rats. In these rats a large increase of the labeling index was found between 24 hours and 1 week, whereas the total number of satellite cells was consistently higher from 2 days on until 2 weeks after running. In the younger animals roughly the same time pattern was observed. CONCLUSION: Since the damage differed in amount and time between the two age groups, we conclude that the quick and huge proliferation response is due to leakage of mitogenic factors through small membrane disruptions that are generated during the exercise itself.

Albumins↗
PubMed1995

Reversion of human prostate tumorigenic growth by azatyrosine.

OBJECTIVES: Azatyrosine, an antibiotic isolated from a Streptomyces species, has been previously shown to have antitumor activity against ras- and neu-transformed fibroblasts and human epithelial cells. In this study, we investigated the effect of azatyrosine on human prostate cancer cell growth and the reversion potential of this antibiotic on prostate tumorigenic cell lines. METHODS: Three androgen-independent human prostate cancer cell lines (TSU-Prl, DU-145, and PC-3) were cultured in the presence of azatyrosine and their growth rates were determined over a 7-day period. Following exhaustive treatment with azatyrosine for 5 weeks, three azatyrosine-resistant colonies were cloned from the PC-3 cell line and were subsequently established as stable cell lines. The growth characteristics of these azatyrosine-resistant clones were examined both in vitro and in vivo to establish their "potentially revertant" profiles. RESULTS: Incubation with azatyrosine (for 7 days) resulted in greater than 95% in vitro growth inhibition of the three parental prostate cancer cell lines. Analysis of the biologic properties of these azatyrosine-resistant cell lines revealed: (1) a significant reduction in in vitro growth rates; (2) a decreased rate of DNA synthesis as measured by thymidine uptake; and (3) a decreased ability for colony formation in soft agar. Moreover all three azatyrosine-resistant clones exhibited suppressed tumorigenicity in severe combined immunodeficient (SCID) mice when compared with the parental cell line. An important observation was that one revertant clone demonstrated complete loss of tumorigenicity. On the basis of this biologic behavior, these cell lines were characterized as revertants. Cytogenetic analysis revealed gross chromosomal differences between the revertant clones and the parental cell line. Northern hybridization analysis demonstrated elevated expression of the K-rev-1 and bcl-2 but not the rrg mRNA transcripts in the revertant cell lines. CONCLUSIONS: These results suggest that azatyrosine inhibits prostate tumorigenic growth; it has a high reversion efficiency on human prostate cancer cells; and the K-rev-1 suppressor gene and the bcl-2 proto-oncogene could be potentially involved in the reversion mechanism mediated by azatyrosine. This reversion of prostate cancer cells to an apparently nontumorigenic phenotype points to a potentially significant therapeutic role for azatyrosine in the treatment of advanced prostate cancer.

Adenocarcinoma↗
PubMed1995

The effects of cognitive impairment on 9-year mortality in a community sample.

Using 9-year mortality data on a community sample of 3,560 adults aged 40 and over, this study assessed the effects of cognitive functioning and one-year declines in cognitive functioning on mortality controlling for comorbid chronic medical illness, physical disability, and psychiatric illness. The study determined the 9-year vital status and, among the decreased, date of death of respondents who were first interviewed in 1980 by the New Haven Epidemiologic Catchment Area Study. Mortality risk by cognitive functioning, as assessed by the Mini-Mental State Examination (MMSE), was estimated using Cox Proportional Hazards Models controlling for baseline assessments of physical and mental health. For both men and women, lower scores on the MMSE decreased the risk of survival, although the effect was stronger for younger respondents than older respondents. Decline in MMSE scores over the course of one year had no additional effect on mortality beyond the resulting MMSE score. Cause-specific mortality was also examined.

Adult↗
PubMed1995

African swine fever virus gene j13L encodes a 25-27 kDa virion protein with variable numbers of amino acid repeats.

The African swine fever virus (ASFV) j13L gene encodes a 177 amino acid protein (19.0 kDa) with a putative transmembrane domain between residues 32 and 52. There is a potential signal peptide cleavage site at residue 54 and several possible motifs for phosphorylation and myristylation. Rabbit antisera raised against a synthetic peptide from the C terminus of the j13L ORF identified proteins of 25-27 kDa in cells infected with a recombinant vaccinia virus expressing the j13L ORF, in ASFV-infected cells and in purified extracellular ASF virions. In ASFV-infected cells the j13L protein was expressed late during infection and exhibited size variation (25-27 kDa) between the different ASFV strains. Nucleotide sequence analysis of the gene in these strains showed that these size differences were due to variation in the number and sequence of tandemly repeated amino acid repeats. Although ASFV-infected animals made antibodies to the j13L protein, no protection was observed when pigs were vaccinated with a recombinant vaccinia virus expressing the j13L ORF.

African Swine Fever Virus↗
PubMed1995

Phase I and clinical evaluation of a pharmacologically guided regimen of suramin in patients with hormone-refractory prostate cancer.

PURPOSE: This phase I study was designed with the following objectives: (1) to describe the overall and dose-limiting toxicity (DLT) of suramin administered by intermittent short intravenous infusions until DLT or disease progression; (2) to determine the ability of an adaptive control with feedback (ACF) dosing strategy to maintain suramin plasma concentrations within a preselected range; (3) to develop a population model of suramin pharmacokinetics; and (4) to identify preliminary evidence of antitumor activity. PATIENTS AND METHODS: Seventy-three patients with advanced, incurable, solid tumors (including 69 with hormone-refractory prostate cancer) received an initial 5- to 7-day daily loading treatment followed by intermittent infusions individually determined by ACF using a Bayesian algorithm and relying on population models of suramin pharmacokinetics. Treatment was given to three cohorts of patients based on target plasma suramin concentration ranges (peak, 30 minutes postsuramin, and trough on morning of the treatment day), as follows: cohort 1, 175 to 300 micrograms/mL (27 patients); cohort 2, 150 to 250 micrograms/mL (23 patients); and cohort 3, 100 to 200 micrograms/mL (23 patients). All patients were to receive suramin until DLT or disease progression. RESULTS: The DLT was most commonly seen in cohort 1 and included a syndrome of malaise and fatigue, associated with weight loss, anorexia, and changes in taste. Other reversible toxicities were neurologic, renal, cutaneous, edema, lymphopenia and anemia, ophthalmologic, and alopecia. Forty of 67 assessable patients (60%) had a 50% reduction and 25 of 67 (37%) a 75% reduction in prostate-specific antigen (PSA) levels that lasted more than 4 weeks, seven of 18 (40%) had measurable responses, and 18 of 37 (49%) demonstrated major pain improvement. The overall times to disease progression and survival were 170 and 492 days, respectively. CONCLUSION: We have characterized all toxicities with suramin in a pharmacologically guided phase I study designed to maintain plasma suramin concentrations of 100 to 300 micrograms/mL (cohorts 1 to 3). The incidence of grade 3 to 4 neurologic abnormalities was relatively low, particularly in cohorts 2 and 3 (100 to 250 micrograms/mL). Evidence of significant and durable antitumor activity was seen in all three cohorts.

Adaptation, Physiological↗
PubMed1995

Laparoscopic monitoring of cryosurgical ablation of the prostate.

Cryosurgical ablation of the prostate has resurfaced as a potential treatment option for organ-confined adenocarcinoma of the prostate. This study examines the temperatures achieved at the anterior prostatic capsule during the freeze-thaw cycle of transperineal cryosurgical ablation of the prostate. Additionally, as there was direct laparoscopic visualization of the prostate, frost forming outside the prostate would have been detected. Two patients underwent endoscopic extraperitoneal pelvic lymphadenectomy followed, with patients under the same anesthetic, by transperineal cryosurgical ablation of the prostate. Nadir prostatic capsular temperatures reached - 28 and - 36 degrees C, respectively, occurring approximately 13 min into the freezing phase. At these temperatures, no frost was observed endoscopically at the ventral surface of the prostate. Ice was palpated with endoscopic probes several millimeters below the ventral capsular surface. These nadir temperatures are lower than those of previous studies on cryosurgical ablation of the human prostate. Further studies need to examine the temperatures required to produce cell death and to determine whether periprostatic tissues can be treated safely and effectively for locally advanced disease.

Adenocarcinoma↗
PubMed1994

Induction of apoptosis in androgen-independent human prostate cancer cells undergoing thymineless death.

Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen-independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen-independent human prostatic cell lines, PC-3 and DU-145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non-androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5-fluoro-2-deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis-related genes, such as TRPM-2/SGP-2, and TGF-beta 1, but not the growth-related genes, c-myc, c-fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine-induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DNA, indicating that this apoptotic process is due to the induction of "thymineless" state. These results suggest that androgen-independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a "thymineless" state.

Apoptosis↗
PubMed1994

Partial growth suppression of human prostate cancer cells by the Krev-1 suppressor gene.

A series of functional studies were performed to assess the potential role of the ras-related transformation suppressor gene, Krev-1, in suppressing prostate cancer cell growth. Three human prostate cancer cell lines, PC-3, TSU-Pr1, and DU-145 were transfected with a plasmid containing the Krev-1 cDNA and a neomycin resistance gene. Selected G418-resistant clones were isolated and expanded into cell lines. All cloned transfectants exhibited a significant reduction in their in vitro growth rates, i.e., longer doubling times, when compared to the parental cell lines. Molecular analysis of the Krev-1 cloned transfectants revealed that they all contained variable copy numbers of the Krev-1 gene and expressed high levels of Krev-1 mRNA transcript, as shown by Southern and Northern analysis, respectively. To determine whether the biological properties associated with tumorigenicity were changed in these Krev-1 transfectants, their growth characteristics were examined on the basis of their ability to a) form colonies in soft agar, and b) produce tumors in SCID mice. The majority of the Krev-1 transfectants from the PC-3 and TSU-Pr1 cell lines showed a substantially reduced ability to form colonies in soft agar and produced significantly smaller tumors when inoculated into SCID mice. In contrast, there was no significant reduction in the soft agar colony-forming ability or in vivo tumorigenicity of the DU-145 Krev-1 transfectants. These results suggest that the Krev-1 suppressor gene induces partial suppression of the malignant phenotype of human prostate cancer cells containing activated ras oncogenes.

Adenocarcinoma↗
PubMed1994

Use of skin conductance changes during mental stress testing as an index of autonomic arousal in cardiovascular research.

Mental stress testing is used to study the cardiovascular changes caused by psychologic stress. To examine the effects of cardiac drugs on mental stress-induced changes, it is useful to attain a degree of arousal that can be replicated in serial studies. Skin conductance level, a cholinergically mediated index of arousal, was assessed for its stability in serial studies and under conditions of beta-blockade. In normal subjects, skin conductance increased in response to mental stress (p < 0.001) and was stable across three sessions. In patients with mild hypertension, skin conductance was elevated during mental stress during both placebo and nadolol therapy (p < 0.001). As expected, nadolol reduced baseline and stress-induced peak arterial pressure and heart rate but had no significant effect on skin conductance. Thus skin conductance level can serve as a stable and useful index of autonomic arousal in clinical trials, even in patients using beta-blocking medications.

Adult↗
PubMed1994

Prostatic ultrasound in the patient without a rectum.

Digital rectal examination, measurement of prostatic-specific antigen, and transrectal ultrasound, with or without prostate biopsy, are the urologist's primary tools for diagnosing carcinoma of the prostate. However, in the patient who has previously undergone abdominoperineal resection of the rectum such procedures are not possible. We therefore describe a simple, cost-effective method for evaluating the prostate in the patient without a rectum, via transperineal ultrasound and prostate biopsy. This procedure provides the urologist with a solution to a heretofore difficult problem.

Adenocarcinoma↗
PubMed1994

Rare incidence of human papillomavirus types 16 and 18 in primary and metastatic human prostate cancer.

OBJECTIVES: The reported data regarding the incidence and significance of human papillomavirus (HPV) in prostate cancer have been inconsistent. In the present study the incidence of HPV 16 and 18 was evaluated in an expanded series of primary as well as metastatic prostate cancer specimens, in order to evaluate a potential role of HPV infection in development and progression of prostate cancer. This is the first study attempting to establish the significance of HPV in metastatic prostate cancer. METHODS: The presence of high risk human papillomaviruses HPV 16 and 18 was analyzed using the polymerase chain reaction (PCR) amplification method and Southern blot hybridization analysis in a total of 61 prostatic tissue specimens: 43 primary prostate adenocarcinoma formalin-fixed, paraffin-embedded specimens, with varying degrees of differentiation (mean Gleason score 5.8, range 3 to 9); 17 pelvic lymph nodes positive for metastatic deposits; and 1 normal prostate specimen. RESULTS: This human papillomavirus typing indicates that only 1 out of the 43 prostatic specimens analyzed was positive for HPV 16 and 1 metastatic lymph node was positive for HPV 18, as revealed by Southern analysis. These results demonstrate the infrequent detection of HPV 16 and 18 DNA in all the primary prostatic adenocarcinoma specimens and metastatic lymph nodes analyzed in this study population. CONCLUSIONS: The negative HPV status for primary and metastatic prostate cancer demonstrated in this study provides a strong argument against an etiological role of HPV infection in the development and progression of the disease.

Adenocarcinoma↗
PubMed1994

The course of psychological distress following threatened and actual conjugal bereavement.

We measured multiple dimensions of distress among spouses (N = 440) of patients hospitalized for serious illness or elective surgery and compared the course of distress over 2 years of follow-up among five groups according to whether and when spouses were bereaved. Distress was related to the severity of the patient's illness, the actuality and timing of the bereavement, as well as the gender and age of the respondent.

Anxiety↗
PubMed1994

Protection elicited by a replication-defective adenovirus vector expressing the tick-borne encephalitis virus non-structural glycoprotein NS1.

Tick-borne encephalitis virus (TBEV) encodes a conserved, immunogenic, non-structural protein NS1 that is glycosylated and secreted from infected cells in an oligomeric form. An adenovirus recombinant, RAd51, expressing high levels of TBEV NS1 has previously been demonstrated to protect mice against a lethal challenge with TBEV. We show here that BALB/c mice infected with TBEV experienced a transient viraemia between days 3 to 5 post-inoculation that was detectable prior to the encephalitic phase of infection. Mice vaccinated with RAd51 were protected against both the viraemic and encephalitic infections associated with the TBEV challenge. Protection was demonstrated to be due to NS1 synthesized de novo from RAd51 in the vaccinated mice. Since TBEV NS1 is expressed on the cell surface, antibody-dependent complement-mediated cytolysis (CMC) of infected cells was considered as a possible mechanism of protection. Vaccination with the recombinant adenovirus proved to be effective in a mouse strain carrying a genetic deletion in the complement receptor C5. CMC is therefore not an essential component of the observed protective immune response.

Adenoviridae↗
PubMed1994

Complications after laparoscopic pelvic lymphadenectomy: CT diagnosis.

OBJECTIVE: Laparoscopic dissection of pelvic lymph nodes has become an accepted alternative to open lymphadenectomy for staging of genitourinary tumors. This study reviews the CT findings in patients with major complications detected after laparoscopic dissection. MATERIALS AND METHODS: Of 85 patients who had laparoscopic dissection of pelvic lymph nodes at our institutions during a 3-year period, complications developed in 12 patients (14%), and eight of these had abdominopelvic CT studies done. CT findings and initial interpretations were correlated with follow-up surgical, clinical, or interventional radiologic findings in all cases. RESULTS: Complications of laparoscopic dissection detected with CT included small-bowel obstruction due to herniation through the trocar site in the abdominal wall (n = 2), extensive hematoma of the abdominal wall or retroperitoneum (n = 2), urinary ascites or multiple urinomas due to ureteral laceration or transection (n = 2), and lymphocele compressing the bladder where the peritoneum was sealed after lymphadenectomy (n = 1). In one case, CT showed pneumoperitoneum but failed to show a perforation of the sigmoid colon. CONCLUSION: Major complications occurred after laparoscopic dissection of pelvic lymph nodes and were diagnosed on the basis of CT findings in seven of eight patients. Recognition of the CT appearances of hernia or hematoma at the insertion sites of the trocars or the laparoscope is important, as is detection of injury to bladder, ureter, bowel, or blood vessels. Symptomatic lymphoceles were infrequently detected, probably because of the use of free drainage into the peritoneal cavity after laparoscopic dissection.

Aged↗
PubMed1993

Homozygous deletion and frequent allelic loss of chromosome 8p22 loci in human prostate cancer.

Allelic loss studies have been instrumental in identifying tumor suppressor gene loci in a variety of cancers. In this study we analyzed prostate cancer specimens from 52 patients for allelic loss using 8 polymorphic probes for the short arm of chromosome 8. Overall, 32 of 51 (63%) informative tumors showed loss of at least one locus on chromosome 8p. The most frequently deleted region is observed at chromosome 8p22-8p21.2. Loss of one allele is identified in 14 of 23 (61%) tumors at D8S163, in 15 of 32 (47%) tumors at lipoprotein lipase, and in 20 of 29 (69%) tumors at MSR, all on 8p22. Loss of one allele is identified in 16 of 27 (59%) tumors at D8S220 at 8p21.3-8p21.2. In addition to frequent loss of one allele at the MSR locus, one metastatic prostate cancer sample demonstrated homozygous deletion of MSR sequences. Loci telomeric and centromeric to this region are largely retained. A chromosome 8p deletion map is constructed and defines the smallest region of overlap to a 14-cM interval at 8p22 between D8S163 and lipoprotein lipase, flanking the MSR locus. Evidence of chromosome 8q multiplication at locus D8S39 was detected in 5 of 32 (16%) tumors, all of which demonstrated loss with at least one probe on chromosome 8p. This study extends the previous finding of frequent loss of chromosome 8p in prostate cancer by defining a common region of loss of heterozygosity at 8p22 and a homozygous deletion of the MSR locus contained within this region. This is the first homozygous deletion identified in the genome of a human prostate cancer and the highest rate of loss yet reported on chromosome 8p in cancer. These results strongly suggest the presence of a tumor suppressor gene in this region which is frequently inactivated in prostate cancer.

Alleles↗
PubMed1993

Suramin, an active drug for prostate cancer: interim observations in a phase I trial.

BACKGROUND: Previous studies indicate that suramin may be an active agent for treatment of solid tumors. The clinical use of suramin is complicated by a broad spectrum of toxic effects and complex pharmacology. Studies have suggested that the dose-limiting neurotoxicity of this agent is closely related to sustained plasma drug concentrations of 350 micrograms/mL or more. PURPOSE: This phase I clinical trial in patients with solid tumors was designed to determine whether plasma concentrations resulting in both antitumor activity and manageable toxicity could be achieved with short, intermittent infusions of suramin. METHODS: Thirty-seven patients, including 33 with metastatic, hormone-refractory prostate cancer, collectively received 43 courses of suramin designed to maintain a plasma concentration range of 200-300, 175-275, or 150-250 micrograms/mL. Patients received a test dose of 200 mg and an initial loading dose of 1000 mg/m2 on day 1 of therapy. Subsequent suramin doses and schedules were individually determined using a strategy of adaptive control with feedback, which used a maximum a posteriori Bayesian algorithm to estimate individual pharmacokinetic parameters. Patients were treated until dose-limiting toxicity or progressive disease developed. RESULTS: Thirty-five of the 37 study patients and 31 of the 33 with prostate cancer were assessable for toxicity and response. Treatment was discontinued in 28 patients because of dose-limiting toxicity consisting of a syndrome of malaise, fatigue, and lethargy; recurrent reduction in creatinine clearance of 50% or more; or axonal neuropathy. Evidence of major antitumor activity was observed in patients with prostate cancer treated at all three plasma drug concentrations. Measurable responses (one complete response and five partial responses) were noted in six of 12 patients with measurable disease. Twenty-four (77%) of 31 patients had a reduction in prostate-specific antigen of 50% or more, and 17 (55%) of 31 had a reduction of 75% or more. Twenty (83%) of 24 patients reported reduction in pain. CONCLUSIONS: Suramin can be safely administered as an intermittent bolus injection by use of adaptive control with feedback to control plasma drug concentrations; toxicity is significant but manageable and reversible. Suramin is active against hormone-refractory prostate cancer. IMPLICATIONS: Future trials should address the role and necessary extent of therapeutic drug monitoring; the optimal plasma drug concentration range and duration of therapy; and the activity of suramin in combination with other agents, in earlier stages of prostate cancer, and in other tumor types.

Aged↗
PubMed1993

Effects of annular cranial vault modification on the cranial base and face.

Artificial modification of the cranial vault was practiced by a number of prehistoric and protohistoric populations, frequently during an infant's first year of life. We test the hypothesis that, in addition to its direct effects on the cranial vault, annular cranial vault modification has a significant indirect effect on cranial base and facial morphology. Two skeletal series from the Pacific Northwest Coast, which include both nonmodified and modified crania, were used: the Kwakiutl (62 nonmodified, 45 modified) and Nootka (28 nonmodified, 20 modified). Three-dimensional coordinates of 53 landmarks were obtained using a diagraph, and 36 landmarks were used to define nine finite elements in the cranial vault, cranial base, and face. Finite element scaling was used to compare average nonmodified and average modified crania, and the significance of the results were evaluated using a bootstrap test. Annular modification of the cranial vault produces significant effects on the morphology of the cranial base and face. Annular modification in the Kwakiutl resulted in restrictions of the cranial vault in the medial-lateral and superior-inferior dimensions and an increase in anterior-posterior growth. Similar dimensional changes are observed in the cranial base. The Kwakiutl face is increased anterior-posteriorly and reduced anterior-laterally to posterior-medially. Similar effects of modification are observed in the Nootka cranial vault and cranial base, though not in the face. These results demonstrate the developmental interdependence of the cranial vault, cranial base, and face.

Cephalometry↗