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Biomedical subjects

S P Lerner

Publications and source records attributed to S P Lerner.

16 recordsLinked to original sources
PubMed1992

Unilateral ovariectomy increases loss of primordial follicles and is associated with increased metestrous concentration of follicle-stimulating hormone in old rats.

The primary objective of these studies was to determine whether unilateral ovariectomy (ULO) would affect rate of loss of primordial follicles. In experiment 1, retired breeder rats, unilaterally ovariectomized and maintained on the experiment for 90 days after surgery, had fewer (p less than 0.01) primordial follicles per ovary than sham-operated controls of the same age. The purpose of experiment 2 was to determine whether time after ULO or age of rats was the critical factor necessary for increased loss of primordial follicles found after ULO in experiment 1. It was found that age was more important than time: when ULO was performed at 30 days of age, the number of primordial follicles did not decrease in ULO rats compared to controls (p greater than 0.05) before 250 days of age. Concentrations of FSH during metestrus were not greater (p greater than 0.05) in ULO rats than in controls until rats were 250 days old. There were also fewer (p less than 0.05) growing follicles per ovary in ULO than in sham-operated rats at 250 days of age. It is concluded that ULO can increase the loss of primordial follicles, but only in old rats (greater than or equal to 250 days of age).

Animals↗
PubMed1992

Polygenic influences on the length of oestrous cycles in inbred mice involve MHC alleles.

Genetic influences on female reproductive cycles were analysed in histocompatibility-congenic strains of mice. Oestrous cycles of young, virgin mice of inbred-congenic strains, hybrid crosses (F1), and parental-hybrid backcrosses (F2) were monitored for 3 months. Oestrous cycles were categorized by length (inter-oestrous interval): 4, 5, 6, or 7-14 days. Mice with the following H-2 haplotypes had a greater proportion of 5-day oestrous cycles: H-2b, H-2r, H-2h2, H-2h4, and H-2i5. In contrast, the H-2k and H-2d haplotypes had mostly 4-day oestrous cycles. Influences of H-2 haplotype were seen on two genetic backgrounds, C57BL/10Sn and C3H. Non-H-2 alleles were also implied by different patterns of cycles between strains with the same H-2b haplotype: C57BL/10Sn with predominantly 5-day cycles vs. C57BL/6J with a mix of 4- and 5-day cycles. The genetic basis for strain differences was investigation in F1 hybrids and their backcrosses. F1 hybrids of an H-2b (C57BL/10Sn; 5-day cycles) and an H-2k (B10.BR; 4-day cycles) strain had mostly 5-day cycles, indicating dominance of an H-2b allele(s). However, F1 hybrids from the reciprocal B6 x B10 cross (both H-2b) also display a preponderance of 5-day cycles, indicating dominance of a non-H-2 autosomal allele from the C57BL/10Sn strain. Among F2 mice, a '4-day' phenotype segregated with homozygosity for the k haplotype (P < 0.05, chi 2). These findings demonstrate the influence of genetic differences at the major histocompatibility complex on oestrous cycles.

Alleles↗
PubMed1992

Radical cystectomy in regionally advanced bladder cancer.

The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.

Carcinoma, Transitional Cell↗
PubMed1991

Ontogeny of corticotropin releasing hormone gene expression in rat hypothalamus--comparison with somatostatin.

Using in situ hybridization histochemistry, corticotropin-releasing hormone gene expression is first detectable in the parvocellular portion of the rat paraventricular nucleus on the 17th fetal day. The prevalence of messenger RNA for corticotropin releasing hormone decreases perinatally, specifically between the 19th and 21st fetal days. By the 4th postnatal day, CRH gene expression is similar to that of the adult rat. Somatostatin messenger-RNA is detectable on the 14th fetal day in the periventricular nucleus. No perinatal hiatus in somatostatin gene expression is evident.

Animals↗
PubMed1991

The risk of dying of prostate cancer in patients with clinically localized disease.

From 1966 to 1979, 360 patients with clinical stages A2, B and C1 prostate cancer underwent staging pelvic lymphadenectomy, and completed a course of combined interstitial radioactive gold seeds and external beam radiotherapy. All patients had a normal serum prostatic acid phosphatase level and a bone scan negative for metastases. All patients were followed until death or for a mean of 7.3 years (range 1.2 to 18.25 years) for those alive at analysis. To determine the risk of dying of prostate cancer we reviewed the records of the 142 patients (39%) who died. At analysis 21% of the patients had died of prostate cancer and 17% of other known causes. The cause of death could not be determined in 4 patients (1%). Cardiovascular disease accounted for a fifth of all deaths. The actuarial risk of death of prostate cancer for all patients was 8 +/- 3% (+/- 2 standard errors) at 5 years and 30 +/- 7% at 10 years. The risk of death of all causes was 16 +/- 4% at 5 years and 46 +/- 7% at 10 years. An increased risk of cancer death was associated with established risk factors, including advanced local disease, poorly differentiated histology, pelvic nodal metastases and distant recurrence. We also noted a substantial risk of cancer death in patients who had local tumor recurrence. While previous studies have reported a relatively low incidence of cancer deaths (4 to 17%) in patients initially diagnosed with localized disease, our data suggest that prostate cancer is the major cause of mortality in such patients. Aggressive curative therapy, regardless of treatment modality, should be considered for localized prostate cancer in men with a life expectancy of 10 or more years.

Actuarial Analysis↗
PubMed1991

Treatment of staghorn calculi with extracorporeal shock-wave lithotripsy and percutaneous nephrolithotomy.

Between August 1983 and August 1987, 72 staghorn calculi were treated in 66 patients. Treatment was with percutaneous nephrolithotomy (PCNL) in 30, extracorporeal shock-wave lithotripsy (ESWL) in 18, combination PCNL-ESWL in 23, and nephrectomy in 1. Complications occurred in 59 percent of patients and were twice as common after PCNL as after ESWL. Radiologic follow-up on 69 kidneys (97%) showed 58 percent were stone-free, 15 percent had residual sand or matchheads less than 5 mm, 17 percent had residual fragments of 5-15 mm, and 10 percent had greater than 15 mm residual stone burden. With a mean follow-up of thirty months, 2 of 40 stone-free patients had persistent asymptomatic Proteus urinary tract infections, and 4 of 22 patients with residual calculi less than or equal to 15 mm required additional operative treatment.

Combined Modality Therapy↗
PubMed1990

Age-related immunohistochemical studies of A and D cells in pancreatic islets of C57BL/6J mice.

Sections of pancreatic islets from C57BL/6J mice aged 3, 14, and 24 months, consisting of islets derived from the dorsal primordium (DPI) and from the ventral primordium (VPI), were immunostained using the peroxidase-antiperoxidase (PAP) procedure for localization of glucagon (A cells) and somatostatin (D cells). The density (A or D cell area/islet area) of immunopositive cells were determined using computer-assisted image analysis. The density of A cells was significantly less in VPI of 14- and 24-month-old mice compared to 3-month-old mice. The density of A cells in 24 month DPI was less than 3 month DPI but no different from 14 month DPI. The mean area (microns 2) of A cells (only in DPI) was significantly less at 24 months compared to the 3 and 14 month groups. There were no differences in somatostatin staining when comparing the three age groups, although at all ages the density of D cells was always greater in the DPI. In conclusion, the major difference between the young and older mice was a deficiency of glucagon-stained cells in older mice. These results might be important in explaining improved glucose tolerance in aged C57BL/6J mice.

Aging↗
PubMed1990

Age-related alterations in follicular development and hormonal profiles in rats with 4-day estrous cycles.

Two experiments were conducted to examine the hypothesis that an alteration in follicular development is associated with advancing maternal age in the absence of prolonged estrous cycles. In Experiment 1, serum and four follicles (from one ovary per rat) were collected from young and middle-aged, 4-day cycling rats on estrus or metestrus. Number and diameter of nonatretic antral follicles greater than 200 microns in diameter were determined from serial sections of the other ovary from each rat. In Experiment 2, serum and follicles (12 +/- 2) from both ovaries were collected from young and middle-aged rats on each day of a 4-day estrous cycle. All microdissected follicles were assayed for estradiol-17 beta (E2) and all sera were assayed for E2, follicle-stimulating hormone, and luteinizing hormone by radioimmunoassay. Numbers of follicles greater than 400 microns in diameter did not differ, while numbers of follicles 200-400 microns in diameter were reduced in middle-aged rats compared to young rats (Experiment 1). The mean diameter of follicles greater than 400 microns in diameter and the follicular content of E2 was greater in middle-aged than in young rats. In Experiment 2, a greater proportion of large follicles were observed in middle-aged rats than in young rats on all days, and a greater proportion of follicles with high concentrations of E2 were observed on diestrus. We interpreted these data as indicative of an early age-related change in the control of follicular recruitment, growth, and maturation.

Aging↗
PubMed1989

Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra.

Long-term effects of lesions were analyzed in terms of gene expression. Nine months after unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (s. nigra), the remaining dopaminergic (DAergic) neurons (tyrosine hydroxylase (TH) cells determined by immunocytochemistry (ICC] on the lesioned side were atrophic with smaller nucleoli. By in situ hybridization, the DAergic neurons on the lesioned side had a 50% smaller TH-mRNA concentration than on the contralateral non-lesioned side. However, beta-tubulin mRNA concentration in DAergic neurons was unaffected by the lesion. The lesions did not alter TH-mRNA concentration in the contralateral non-lesioned side by comparison with unoperated controls. We propose that chronic lesions have long-term effects on gene expression because of damage sustained during compensatory hyperactivity after the lesion, or because of decreased trophic support from other neurons.

Animals↗
PubMed1989

Infection stones.

The pathogenesis and epidemiology of infection stones are well understood. While percutaneous lithotripsy and extracorporeal shock wave lithotripsy have emerged as the mainstay of extirpative therapy, surgical lithotomy is the standard to which other therapies must be compared. Adjunctive therapy with pharmacological agents that inhibit urease with few side effects and effective urinary acidifiers favor chemolysis. Diet and chemotherapy offer the hope of slowing stone growth and/or recurrence in patients with chronic urease-producing bacteriuria.

Humans↗
PubMed1988

Genotypic influences on reproductive aging of inbred female mice: effects of H-2 and non-H-2 alleles.

The H-2 (major histocompatibility) complex of mice influences a variety of physiologic parameters. This study describes the influences of H-2 polymorphisms and other genetic influences on age-related changes (5-20 mo) in estrous cycles and fecundity. We monitored estrous cycles of virgin or retired-breeder mice of congenic strains on the background of C57BL/10Sn (B10):B10.BR/Sg (B10.BR) and B10.RIII/Sn (B10.RIII). For another comparison, we examined the C57BL/6J (B6) strain, which has the same H-2 haplotype as the B10. Estrous cycles were categorized by length during 10 mo of observations. From 5 to 15 mo of age, B10 and B10.RIII mice displayed a preponderance of 5-day cycles, B10.BR mice displayed a preponderance of 4-day cycles, and B6 mice had diminishing numbers of 4-day cycles. Age-related acyclicity differed with strain, particularly among retired breeders; B6 mice had an earlier onset and more rapid increase of acyclicity with age than the B10 congenic mice. Litters/female, maternal age at last litter, and total pups/female differed with strain; B10.BR and B10.RIII were similar and both had greater values than B10 mice. In conclusion, reproductive senescence of female mice was influenced by genes at the H-2 locus and elsewhere.

Aging↗
PubMed1988

Rapid corticosterone-induced changes in gene expression in rat hippocampus display type II glucocorticoid receptor specificity.

Corticosteroids influence a wide range of neuronal activities by binding to either of two different glucocorticoid receptors found in rat brain. To investigate genomic responses in brain to stress levels of circulating corticosterone (CORT), we isolated hippocampal total RNA and poly(A)-containing RNA from rats treated with 10 mg/day CORT or vehicle. RNA translation products were resolved by 2-dimensional gel electrophoresis and fluorography. Select changes in four translation products after acute CORT treatment were inferred from up to 100-fold increases in three polypeptides and a 2-fold decrease in another. While adrenalectomy decreased levels of the inducible RNA sequences (adrenalectomized vs. intact controls), CORT increased the inducible sequences above their levels in intact controls. Rapid increases within 2 h of CORT treatment were seen for RNAs coding for 35, 33, and 20 kilodalton polypeptides. However, RNA coding for a 50 kilodalton polypeptide had a delayed decrease, first seen after 32 h CORT. The CORT increases displayed type II glucocorticoid receptor-specificity: RU 28362 greater than or equal to CORT greater than aldosterone greater than dihydrotestosterone = control. Since type II receptors are only substantially occupied by stress levels of CORT, these changes in gene expression are candidates for molecular stress responses in the brain.

Animals↗
PubMed1986

Age, dose of FSH and other factors affecting superovulation in Holstein cows.

Effects of age of donor and other factors on superovulation and production of transferable embryos were investigated. Data were obtained on 987 recoveries of embryos performed between November 1980 and June 1984 by Select Embryos, Inc. The 339 Holstein donors ranged in age from 1.8 to 17.8 yr. The effects of age of donor and dose of follicle stimulating hormone (FSH) were examined using regression analysis. For on-farm recoveries, numbers of embryos, rates of fertilization, quality scores of all embryos and numbers of transferable embryos decreased (P less than .01, P less than .001, P less than .05, P less than .01, respectively) with increasing age of donor. For in-clinic recoveries, numbers of embryos plus ova recovered were affected by age of donor, dose of FSH and the interaction of the two (P less than .05). Among older donors, increasing doses of FSH were associated with an increase in the number of ova plus embryos recovered. However, among younger donors, increasing doses of FSH had a negative effect. Numbers of embryos, rates of fertilization and numbers of transferable embryos decreased (P less than .05) with advancing age and increased (P less than .05) with increasing doses of FSH. Greater numbers of ova plus embryos were recovered when treatment with FSH was begun on d 10 or 11 as compared with d 7, 8, 9, 12, 13 or 14 (P less than .001). It was concluded that an increase in age of donor had a negative influence on the success of superovulation and the production of transferable embryos, and that the response to FSH was affected by age of donor.

Animals↗
PubMedDate not supplied

Combined in situ hybridization and immunocytochemistry in the assay of pharmacological effects on tyrosine hydroxylase mRNA concentration.

An assay for tyrosine hydroxylase (TH) mRNA by in situ hybridization in combination with immunocytochemistry (ICC) for TH on the same section is described. The in situ hybridization protocol was optimized for [35S]cRNA (complementary RNA, i.e. anti-sense strand) probe concentration and time of hybridization. The specificity of hybridization was measured by several critera. The advantage of measuring grain density versus grains per cell is discussed for quantitation of in situ autoradiography. Finally, the reserpine-induced increase in adrenal TH mRNA was used to validate quantitative aspects of the in situ hybridization technique by comparison with blot hybridization. In contrast to the adrenal, reserpine did not increase TH mRNA in substantia nigra (s. nigra) neurons as measured by either technique.

Animals↗