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Biomedical subjects

A Kirschenbaum

Publications and source records attributed to A Kirschenbaum.

17 recordsLinked to original sources
PubMed1992

A diverged homeobox gene is involved in the proliferation and lineage commitment of human hematopoietic progenitors and highly expressed in acute myelogenous leukemia.

HB24 is a diverged homeobox gene known to be expressed in hematopoietic progenitor cells. We show here that the inhibition of HB24 expression in CD34+ bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation of these cells in response to interleukin-3 and granulocyte-macrophage colony-stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides also reduced the levels of c-fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger RNAs compared with cells treated with control oligonucleotides. Conversely, the transient transfection of HB24 into a subpopulation of CD34 cells inhibited their differentiation into mature hematopoietic cell types. In addition, HB24 messenger RNA transcripts were elevated in bone marrow and peripheral blood mononuclear cells isolated from patients with acute myelogenous leukemia compared with normal controls. These data suggest that HB24 is an important transcription factor during hematopoietic progenitor proliferation and that differentiation to specific cell types requires its downregulation. Furthermore, dysregulated expression of HB24 impairs the normal differentiation of hematopoietic progenitors and may contribute to leukemogenesis.

Antigens, CD↗
PubMed1992

The effect of dihydrotestosterone and culture conditions on proliferation of the human prostatic cancer cell line LNCaP.

Cell density, nutritional state, and serum factors modify the growth response of LNCaP human prostatic cancer cells to dihydrotestosterone. Evaluation of growth response to dihydrotestosterone requires logarithmic transformation of cell count or thymidine incorporation data. Under conditions of dose response, growth increases with cell density but no significant interaction of dihydrotestosterone with cell density was found under optimal culture conditions. The frequency of media change was a significant factor in modulating dose response. When cells from cultures maintained at different feeding periods were plated at different cell densities of (trypan blue) viable cells, significant effects of plating density on dihydrotestosterone response were found. Dihydrotestosterone protects cells under the adverse effects of media deprivation. Under the extreme adverse effects of serum deprivation, cells respond to dihydrotestosterone even under conditions of increasing cell loss. The effects of dihydrotestosterone on final cell density were significant. In the absence of serum, the elongated cells of LNCaP assume a round shape, but many remain adherent to the culture dish and can be restored to normal morphology by serum. A number of growth factors fail to restore normal morphology that was completely restored by a combination of fibronectin and dihydrotestosterone. We have not developed a practicable serum-free system for LNCaP.

Biological Factors↗
PubMed1992

The effect of androgen, estrogen, and growth factors on the proliferation of cultured fibroblasts derived from human fetal and adult prostates.

Stromal enlargement plays a key role in the development of benign prostatic hypertrophy in humans. Human prostatic fibroblasts were obtained from fetal and adult prostates and characterized as to their androgen and estrogen receptor status and growth in response to dihydrotestosterone (DHT), estradiol (E2), hydroxyflutamide (OH-FLU), hydrocortisone, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). In addition, the ability of hormones and growth factors to induce the messenger RNA (mRNA) for the c-fos protooncogene was assessed as a measure of the early, direct effects of these compounds on cellular proliferation. Nuclear androgen receptors were demonstrable by immunocytochemistry in both fetal and adult cells. Nuclear estrogen receptor staining was negative. Neither E2 nor hydrocortisone increased cellular proliferation. Both EGF and bFGF did increase cellular growth. DHT (10(-8)-10(-7) M) had a significant stimulatory effect on cell growth only in serum-free media. OH-FLU addition enhanced DHT induced proliferation. Changing the media during the course of the experiment obliterated the stimulatory effect of DHT. Both EGF (10 ng/ml) and bFGF (20 ng/ml) increased the mRNA for the c-fos protooncogene. DHT (10(-7) M) did not induce the mRNA for c-fos. We conclude that EGF, bFGF, and DHT (especially in combination with OH-FLU) increase the proliferation of human prostatic fetal and adult fibroblasts in vitro. E2 has no effect on fibroblast proliferation. The stimulatory effects of EGF and bFGF are direct, whereas the effect of DHT appears to be indirect, possibly mediated via the increased production and/or secretion of growth factors.

Cell Division↗
PubMed1992

The 24/25-kDa serum insulin-like growth factor-binding protein is increased in elderly women with hip and spine fractures.

Fractures of the hip in elderly women represent a clinical syndrome (age-related osteoporosis) often marked by decreased calcium absorption and secondary hyperparathyroidism. We studied 13 elderly women with fractures of the hip and spine and 18 healthy similarly aged control women to determine whether serum insulin-like growth factor-I (IGF-I) or its carrier binding proteins (IGFBPs) were altered in this syndrome. Serum IGF-I concentrations were not different in the two groups (P = 0.50), but immunoreactive PTH was significantly higher in the fracture group (58.50 +/- 8.20 vs. 13.50 +/- 2.70 ng/L; P less than 0.003). Binding of [125I]IGF-I to IGFBP-3, IGFBP-2, and IGFBP-1, measured by ligand blotting, was not statistically different in the 2 groups, but binding intensities for the serum 24/25-kDa IGFBP were approximately 2.5 times greater in fracture women than control women (P less than 0.0005). In data pooled from both groups, PTH correlated strongly (r = 0.70; P less than 0.0001) with the relative binding intensities for the 24/25-kDa IGFBP. Based on previous work, we speculate that production of the 24/25-kDa IGFBP, which in vitro is known to inhibit IGF-I- and IGF-II-mediated osteoblast function, may be stimulated by PTH in patients with the syndrome of age-related osteoporosis.

Aged↗
PubMed1991

Effect of the addition of estrogen to medical castration on prostatic size, symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy.

A total of 4 men with benign prostatic hypertrophy who underwent medical castration therapy with a long-acting gonadotropin-releasing hormone agonist (leuprolide) for more than 6 months elected to add an estrogen transdermal patch (0.05 mg. to the skin biweekly) to the leuprolide regimen. The average prostatic size (transrectal ultrasound), serum prostate specific antigen (PSA) levels and symptoms of prostatism were dramatically decreased with leuprolide alone. The addition of estrogen for 6 months did not result in any change in prostate size, symptoms or serum PSA levels over that seen with leuprolide alone. The development of squamous metaplasia was noted in 1 man with leuprolide alone and in 1 man after the addition of estrogen. Immunohistochemical staining with anticytokeratin 903 antibodies reveals that squamous metaplasia appears to arise from prostatic basal cells. We postulate that the target cell for estrogen action in the prostate is the prostatic basal cell. In the absence of androgen the only direct effect of estrogens is the induction of squamous metaplasia.

Aged↗
PubMed1990

Serum of patients with prostatic cancer or benign prostatic hypertrophy contains nonpolar testosterone.

We have previously described a nonpolar form of radioimmunoassayable serum testosterone (NPT) not measured by available antitestosterone antibodies. It is detected by mild alkaline hydrolysis of the petroleum ether extract of serum and subsequent radioimmunoassay. The properties of NPT are consistent with that of a fatty acid ester of testosterone or dihydrotestosterone. The serum of young males contains 1 to 3 ng/ml NPT, but it is not detected in female serum. We measured serum testosterone and NPT levels in 36 men between 58 and 87 years of age. Seventeen subjects with advanced prostatic cancer (NPT 1.70 +/- 1.44 ng/ml) were compared with a control group consisting of six patients with benign prostatic hypertrophy (BPH) and 13 patients with no prostatic disease (NPT 0.72 +/- 0.46, P = 0.017). There was no significant difference between BPH patients and patients with no prostatic disease; the results were pooled. The concentration of NPT in prostatic cancer patients but not in controls was inversely correlated with that of testosterone. Immunoassayable testosterone was present in the serum of two orchiectomized patients and, therefore, cannot derive solely from the testes.

Aged↗
PubMed1989

Serum prostate-antigen levels in patients with benign prostatic hypertrophy treated with leuprolide.

We studied serum prostate-specific antigen levels in 12 men with benign prostatic hypertrophy treated with a long-acting GnRH analogue, leuprolide, 1 mg (0.2 mL) sc. daily for six months. The average decrease in prostate size measured by ultrasound was 45 percent after six months with concomitant improvement in the obstructive symptoms of prostatism. There was a steady decline in serum PSA levels which paralleled the decrease in prostate size. One patient who discontinued treatment after six months demonstrated both a regrowth of his prostate and a rise in serum PSA levels to pretreatment levels four months post-discontinuation of treatment. We conclude that treatment with a GnRH analogue caused reversible involution of prostatic epithelial cells with parallel effects on serum PSA levels. Consideration of the initial prostate size together with the serum PSA levels can help predict the response to medical castration in men with BPH.

Antigens, Neoplasm↗
PubMed1989

Effect of long-acting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy.

To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen.

Aged↗
PubMed1988

Penile prostheses.

Penile prostheses represent the most often used approach to the surgical management of impotence. These devices can be classified into semirigid and inflatable types. The advantages and disadvantages of each type as well as a description of their construction are provided here. Appropriate images are provided to illustrate the components of the various devices available.

Erectile Dysfunction↗
PubMed1988

Biliary obstruction complicating extracorporeal shock wave lithotripsy.

An elderly woman with a solitary right kidney and unrecognized cholelithiasis underwent extracorporeal shock wave lithotripsy for renal calculi. Postoperatively, biliary obstruction developed that required emergency surgery. Pathological evaluation of the biliary calculi revealed superficial fragmentation. It is suggested that extracorporeal shock wave lithotripsy was responsible for the gallstone fragmentation and resultant bile duct obstruction.

Aged↗
PubMed1988

Controversies in urologic oncology.

The persistent controversies that characterize urologic oncology reflect the significant advances that have been made in our understanding of genitourinary malignancy and the objective posture that has been taken both by those active in this area and by those whose interests are more indirect. Ultimately, the beneficiaries of these controversies are the patients and their physicians. As continued problems are recognized and investigations are designed to explore them, controversy and skepticism become a healthy concomitant so that true knowledge and understanding can be achieved and such issues ultimately resolved.

Carcinoma in Situ↗
PubMed1987

Preclinical evaluation of PDS (polydioxanone) synthetic absorbable suture vs chromic surgical gut in urologic surgery.

A variety of suture materials are available for use in urologic surgery. Urologists have relied on absorbable suture materials which provide transient strength in anticipation that healing will occur before the suture is absorbed. Absorbable sutures thus decrease the chance of stone formation, known to occur on suture material in direct contact with the urinary stream. This report compares the breaking strength retention of polydioxanone (PDS) suture and chronic surgical gut after in vivo residence in the urinary bladder and subcutaneous tissue of the dog.

Animals↗
PubMed1987

Effect of a GnRH analogue (leuprolide) on benign prostatic hypertrophy.

To determine the effects of reversible medical castration on prostatic size in patients with benign prostatic hypertrophy (BPH), 3 patients with BPH were treated with a GnRH analogue, leuprolide, for six months at a dosage of .2ml (1 mg) s.c. daily. Serum testosterone, dihydrotestosterone and estradiol fell to castration levels 4-6 weeks after the initiation of treatment and remained low throughout the study period. Transrectal ultrasonography of the prostate demonstrated an average decrease in prostatic volume of 58% at 6 months, with the greatest rate of decrease occurring during the 2nd to 5th months of treatment. One man who had acute urinary retention before treatment was subsequently able to void extremely well. In a second man the symptoms of prostatism diminished but in the third urinary frequency and nocturia persisted in spite of a reduction in prostatic size, presumably because his symptoms were due to renal insufficiency.

Aged↗