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B L Dalkin

Publications and source records attributed to B L Dalkin.

26 records · Page 2Linked to original sources

Expression of hemidesmosomal and extracellular matrix proteins by normal and malignant human prostate tissue.

The progression of prostate carcinoma may be influenced by the biochemical nature of the basal lamina surrounding the primary carcinoma cells. As a first step toward understanding this process, the composition and structure of the basal lamina in normal prostate, prostatic intraepithelial neoplasia, and human carcinoma were determined. In addition, a comparison was made between the attachments of the normal basal cell to its underlying basal lamina and those made by primary prostate carcinoma. The normal basal cells form both focal adhesions and hemidesmosomal-like structures as observed by transmission electron microscopy. The normal basal cells exhibited a polarized distribution of hemidesmosomal associated proteins including BP180, BP230, HD1, plectin, laminin-gamma 2(B2t), collagen VII, and the corresponding integrin laminin receptors alpha 6 beta 1 and alpha 6 beta 4. The expression and distribution pattern of these proteins were retained in the prostate intraepithelial neoplasia lesions. In contrast, the carcinoma cells uniformly lacked hemidesmosomal structures, the integrin alpha 6 beta 4, BP180, laminin-gamma 2 (B2t), and collagen VII but did express BP230 (30%), plectin, HD1 (15%), and the integrin laminin receptors alpha 3 beta 1 and alpha 6 beta 1. These results suggest that, although a detectable basal lamina structure is present in carcinoma, its composition and cellular attachments are abnormal. The loss of critical cellular attachments may play a role in influencing the progression potential of prostate carcinoma.

Carcinoma↗

Dithiothreitol effects on human sperm quality.

Human semen normally coagulates immediately after ejaculation and then undergoes liquefaction during the next 15 to 60 minutes. Incomplete seminal liquefaction can result in impaired sperm motility and make clinical evaluation and manipulation difficult. Dithiothreitol, a mucolytic agent that reduces the mucoprotein disulfide bonds in sputum, has been found to induce liquefaction of incompletely liquefied semen in vitro. We studied the effects of dithiothreitol on sperm motility, viability, acrosomal integrity and morphology. A semen sample was provided by 45 healthy, young men at the University of Arizona. Of the specimens 10 (22%) demonstrated incomplete liquefaction. Sperm motility and motion characteristics of untreated (control) semen and semen treated with dithiothreitol were objectively evaluated using computer assisted semen analysis. Sperm cell membrane integrity and mitochondrial integrity were measured by fluorescence microscopy using the deoxyribonucleic acid specific fluorochrome propidium iodide and the mitochondria specific fluorochrome rhodamine-123, respectively. Acrosomal integrity was determined using the fluorescent stain chlortetracycline. Sperm morphology was evaluated using bright field microscopy. For completely liquefied semen (35 cases) dithiothreitol reduced sperm motility (59.1 +/- 1.2% untreated versus 53.2 +/- 1.2% treated, p < 0.01) and motion characteristics. However, dithiothreitol had no statistically significant effect on motility on sperm in the group with incompletely liquefied semen (10 cases). Sperm cell membrane, mitochondrial and acrosomal integrity was unaffected by dithiothreitol regardless of liquefaction status. Dithiothreitol caused a significant increase in abnormally large sperm head morphology in the group with completely liquefied semen. The minimal effects of dithiothreitol on sperm motility traits and viability support its use as a possible aid in the evaluation and manipulation of incompletely liquefied semen.

Acrosome↗

Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves.

We present the results of a prospective multicenter clinical trial of nearly 5,000 men in which prostate specific antigen (PSA) density was compared to the serum PSA concentration alone for early detection of prostate cancer. All men were evaluated with PSA and digital rectal examination. If PSA was elevated (greater than 4 ng./ml., Hybritech Tandem assay) or digital rectal examination was suspicious, transrectal ultrasound guided biopsies were recommended. Prostate volume was estimated by transrectal ultrasound measurements using a prolate ellipse volume calculation and PSA density was calculated by dividing serum PSA concentration by gland volume. Using a PSA density cutoff of 0.15 as recommended in the literature enhanced specificity but at the cost of missing half of the tumors. Of the organ confined neoplasms 47% were detected by a PSA of greater than 4.0 ng./ml. but they were missed by a PSA density of more than 0.15. PSA density may not be predictive for cancer because accurate estimation of transrectal ultrasound volume is difficult (r = 0.61 for estimated transrectal ultrasound volume versus pathological prostate weight). However, a relationship does exist among transrectal ultrasound volume, PSA and positive predictive value for cancer. PSA concentrations of less than 4.0 ng./ml. did not indicate a need for biopsy (positive predictive value 12 to 17%) unless the digital rectal examination findings were suspicious for cancer. A high percentage of patients with a PSA of more than 10 ng./ml. had cancer (30 to 75%), regardless of gland size. Patients with intermediate PSA concentrations (4.1 to 9.9 ng./ml.) and a gland size of 50 cc or less had a 35 to 51% positive predictive value, while those with intermediate PSA concentrations and a large gland (more than 50 cc) had a 15% positive predictive value. We conclude that in men with a PSA level of 4.1 to 9.9 ng./ml., and normal digital rectal examination and transrectal ultrasound findings, the use of a PSA density cutoff of more than 0.15 for biopsy results in half of the tumors being missed. Thus, we recommend that men in this group undergo biopsy based upon serum PSA concentration rather than PSA density.

Aged↗

Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate.

The epithelial basal lamina composition and integrin expression profile of normal and neoplastic human prostate was characterized using immunohistochemical analysis of frozen samples. The major components of the basal lamina surrounding normal acini were laminin, type IV collagen, entactin, and type VII collagen with variable amounts of tenascin. The basal lamina of neoplastic acini had a similar composition, except for the loss of type VII collagen, which was observed in all grades of carcinoma. The basal cells of the normal prostate express the alpha 6-, beta 1-, and beta 4-integrin subunits, suggesting that both the alpha 6 beta 1- and alpha 6 beta 4-integrin complexes are formed. In prostate carcinoma there is a complete loss of beta 4 expression and the alpha 6- and beta 1-integrin subunits, which are restricted to the basal and basal lateral surfaces of basal cells, are distributed diffusely throughout the cytoplasmic membrane. The differential expression of type VII collagen and beta 4 are discussed in relationship to their possible role in tumor progression.

Aged↗

Prostate specific antigen levels in men older than 50 years without clinical evidence of prostatic carcinoma.

In their derivation of normal prostate specific antigen (PSA) levels (0 to 4.0 ng./ml.) Hybritech used almost exclusively men less than 60 years old. The purpose of this study was to define PSA levels by age decade in men older than 50 years without clinical evidence of prostatic carcinoma or so-called cancer-free. We define the cancer-free population as men with a PSA less than or equal to 4.0 ng./ml. and nonsuspicious digital rectal examination, and those with an abnormality in either parameter with a nonmalignant prostate biopsy. A total of 755 men was recruited for a prostate cancer detection study using serum PSA and digital rectal examination, of whom 728 fulfilled our criteria of cancer-free. Newly derived mean and standard deviation were 1.32 +/- 1.10 ng./ml. in the 50 to 59-year group, 1.91 +/- 1.72 ng./ml. in the 60 to 69-year group and 2.36 +/- 1.98 ng./ml. in the 70 to 79-year group. The upper limits for PSA (mean+2 standard deviations) by age were 3.5 ng./ml. in the 50 to 59-year group, 5.4 ng./ml. in the 60 to 69-year group and 6.3 ng./ml. in the 70 to 79-year group. The apparent accuracy of these new limits is strong in the 60 to 69-year group but it declines in the next decade. The data support further attempts at using PSA, age and digital rectal examination to establish selection criteria for prostate biopsy with adequate sensitivity and specificity.

Age Factors↗

The effects of ultrasound-guided shock waves during early pregnancy in Sprague-Dawley rats.

Pregnancy is a contraindication to extracorporeal shock wave lithotripsy (ESWL) because of its possible harm to the embryo or fetus caused by shock waves or ionizing radiation. In this study timed-pregnant rats were subjected to shock waves early in gestation using a lithotriptor having ultrasound imaging. In a pilot group undergoing immediate laparotomy, it was determined to what extent the pelvic structures were effected. Then a test group was exposed to shock waves and carried to near term pregnancy along with an identical group of pregnant, sham procedure rats. A laparotomy all were inspected for fetal viability, fetal abnormalities, and maternal organ damage. Fetuses located nearest the focal area of maximum shock wave energy showed lower mean weight than controls. There was no recognizable gross or microscopic fetal damage.

Animals↗

Venogenic impotence following dermal graft repair for Peyronie's disease.

Peyronie's plaque excision with dermal grafting generally offers good cosmetic results for patients who require surgical intervention for Peyronie's disease. However, postoperative impotence has been reported in 12 to 100% of such patients. The mechanism of impotence in this setting is not well defined. We present 3 men who had venogenic impotence after plaque excision and dermal grafting for Peyronie's disease. One patient has subsequently responded well to dorsal vein ligation, 1 has chosen an effective nonoperative method of management and 1 continues to consider the options. We report venous leak as an organic cause of impotence after plaque excision and dermal grafting for Peyronie's disease, and its successful management by dorsal vein ligation. The implications of these findings in the surgical management of Peyronie's disease are discussed.

Adult↗