[Relationship of clinicopathological features and chemotherapeutic outcomes in women with BRCA1 and BRCA2 mutation-negative familial breast cancer].

OBJECTIVE: To explore the relationship of clinicopathological features and response to neoadjuvant chemotherapy in women with BRCA1 and BRCA2 mutation-negative familial breast cancer. METHODS: A total of 6 200 women with breast cancer were treated at our hospital from October 2003 to December 2012. All subjects underwent genetic testing for BRCA1 and BRCA2 genes. Patients with BRCA1 and BRCA2 mutations were excluded. This cohort of 5 842 patients with BRCA1 and BRCA2 mutation-negative breast cancer was classified as two groups: familial breast cancer patients (n=480) and sporadic breast cancer patients (n=5 362). The clinicalpathological data and response to neoadjuvant chemotherapy of the 480 patients with BRCA1 and BRCA2 mutation-negative familial breast cancer and the 5 362 patients with BRCA1 and BRCA2 mutation-negative sporadic breast cancer were compared retrospectively. Then the influencing factors of response to neoadjuvant chemotherapy were analyzed. RESULTS: Among the BRCA1 and BRCA2 mutation-negative breast cancer patients, 4.4% of the patients were diagnosed before 30 years of age in the familial breast cancer group, significantly higher than that of 2.6% in the sporadic breast cancer group(P=0.020). 5.0% of the patients in the familial breast cancer group had bilateral breast cancer, significantly higher than that of 2.7% in the sporadic breast cancer group (P=0.004). Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer patients, the relative risk of early-onset breast cancer (≤ 30 years) and bilateral breast cancer were 1.73 and 1.91, respectively, significantly higher than that in the BRCA1 and BRCA2 mutation-negative familial breast cancer cases (P=0.020 and P=0.004). 2 964 patients in this cohort of 5 842 case sreceived neoadjuvant chemotherapy.The pathologic complete response (pCR) rate was significantly higher in the BRCA1 and BRCA2 mutation-negative familial breast cancer group than in the BRCA1 and BRCA2 mutation-negative sporadic breast cancer group (21.7% vs. 14.0%, P=0.001). Independent factors associated with pCR in BRCA1 and BRCA2 mutation-negative breast cancer patients were tumor size less than 2 cm (P=0.012), histologic grade Ⅲ (P<0.001), triple-negative breast cancers (P<0.001), and BRCA1 and BRCA2 mutation-negative familial breast cancer(P=0.001). CONCLUSIONS: Compared with BRCA1 and BRCA2 mutation-negative sporadic breast cancer, BRCA1 and BRCA2 mutation-negative familial breast cancer is more likely diagnosed before the age of 30 years and has a higher risk to develop bilateral breast cancer. BRCA1 and BRCA2 mutation-negative familial breast cancers are more likely to respond to neoadjuvant chemotherapy than BRCA1 and BRCA2 mutation-negative sporadic breast cancer.

[Analysis of clinical characteristics and factors associated with short term outcomes in early term neonates].

Objective: To investigate the clinical characteristics of early term and full term neonates, and analyze the risk factors associated with short term outcomes in early term neonates. Method: Neonates with birth weight (BW) ≥2 500 g from year 2013 were analyzed retrospectively based on American Congress of Obstericians & Gynecologists (ACOG) latest definition of term infants. According to inclusion and exclusion criteria, early term (gestational age 37-38 weeks) and full term(gestational age 39-40 weeks) neonates were included, whose morbidity constituent proportion was analyzed by χ(2) test or Fisher accuracy test or t test or Wilcoxon test. Risk factors associated with short term outcomes in early term population were analyzed by Logistic regression analysis. Result: There were 3 002 discharged term infants being investigated, among whom 1 303 cases were included(768 males and 535 females), and 37, 38, 39 and 40 weeks' gestational age newborns were 160, 324, 450 and 369 respectively. Compared with full term neonates(n=819), early term neonates (n=484) had longer length of hospital stay (LOS)(6.0(5.0, 9.0) vs. 6.0(4.0, 8.0), Z=2.830, P=0.005), higher usage rate of intravenous antibiotics(86.4%(418/484) vs. 80.1%(656/819), χ(2)=8.009, P=0.005), higher assisted ventilation rate(9.5%(46/484) vs. 2.9%(24/819), χ(2)=25.528, P<0.01), higher pulmonary surfactant administration rate(4.3%(21/484) vs. 1.1%(9/819), χ(2)=14.006, P<0.01), as well as higher hypoglycemia incidence(3.9%(19/484) vs. 1.2%(10/819), χ(2)=10.226, P=0.001). There were no statistically significant differences in 1 min Apgar score (9(9, 10)vs. 9(9, 10), Z=0.860, P=0.390), 5 min Apgar score (10(9, 10) vs. 10(9, 10), Z=0.810, P=0.418), white blood cell count (15 (11, 21) ×10(9) /L vs.15 (11, 22) ×10(9) /L, Z=0.880, P=0.379), hemoglobin count(180 (159, 205) vs. 182 (160, 204) g/L, Z=0.560, P=0.576), or platelet count(303(234, 372) ×10(9)/L vs. 301(237, 391) ×10(9)/L, Z=0.550, P=0.584). BW between 2 500 g and 2 999 g(OR 1.69, 95% CI: 1.10-2.62, χ(2) =5.614, P=0.018), wet lung(OR=2.61, 95% CI: 1.61-4.24, χ(2)=15.023, P=0.000)and pneumonia(OR 1.88, 95% CI: 1.14-3.08, χ(2)=6.192, P=0.013) were risk factors in early term neonates' short term adverse outcomes. Conclusion: Early term newborns are still at their "immature" state, and respiratory disorders are major risk factors associated with short term outcomes. Hence, early delivery during 37-38 weeks should be avoided as possible as we can.

Tamoxifen stimulates human papillomavirus type 16 gene expression and cell proliferation in a cervical cancer cell line.

The widely adopted use of tamoxifen as a chemotherapeutic agent is primarily based on its inhibition of cancer cell growth. However, we report that tamoxifen at low concentrations (10(-9) and 10(-11) M) causes stimulation of cell proliferation in a cervical cancer cell line, SFR. The facts that SFR cells do not contain estrogen receptors and are estrogen nonresponsive imply the existence of an antiestrogen-specific binding protein and suggest that the effect of tamoxifen is possibly mediated through a pathway other than estrogen receptors. Tamoxifen at low concentrations stimulated human papillomavirus type 16 (HPV-16) gene transcription and E7 protein production. Levels of HPV-16 mRNA and E7 protein reached a peak at approximately 2-4 h after tamoxifen treatment, persisted for several hours, and subsequently decreased to their prestimulation levels by about 24 h after treatment. Our results indicate for the first time that tamoxifen stimulates cell proliferation of cervical cancer cells, and we suggest that the enhanced HPV-16 mRNA and E7 protein levels are probably responsible.

A gene near the D3F15S2 site on 3p is expressed in normal human kidney but not or only at a severely reduced level in 11 of 15 primary renal cell carcinomas (RCC).

Renal Cell Carcinoma (RCC) has been associated with the loss of heterozygosity at several loci on the short arm of chromosome 3 (3p). We have previously found that one of these loci, D3F15S2 (pH3H2) was lost in 76% of the tumor cells derived from heterozygous donors (Kovacs, G., Erlandsson, R., Boldog, F., Ingvarrsson, S., Müller-Brechlin, R., Klein, G. & Sümegi, J. (1988), Proc. Natl. Acad. Sci., 85, 1571-5). More recently we have identified a putative CpG island in the vicinity of D3F15S2, suggesting that DNA sequences in or around this site may have coding potential (Boldog, F., Erlandsson, R., Klein, G. & Sümegi, J. (1989). Cancer Genet. Cytogenet., 42, 295-306). The screening of a human placenta cDNA library with DNA probes derived from D3F15S2 has led to the isolation of several cDNA clones. They identified a 2.9 Kb long message in human placenta and kidney. In total RNA from 11 of 15 primary RCCs the gene expression was reduced to less than 20% compared to eight normal kidneys. This low level of expression may be due to contaminating normal tissue. In the remaining 4 tumors the expression varied from 24-51% compared to normal kidney. To facilitate reference, the gene was provisionally designated as 'RIK'. It was expressed in the HEK 293, one osteosarcoma (HOS), two carcinoma (COLO320 and QDMT), and three Burkitt lymphoma lines (BL2, BL29 and BL31). It was not expressed in one Burkitt lymphoma (DG75) and two EBV transformed lymphoblastoid cell lines (LCL) (NAD-20 and Cherry).

Association of endosperm reduction with parental imprinting in maize.

Among 38 reciprocal translocations between the maize B chromosome and the proximal region of the long arm of chromosome 10 were six interchanges associated with reduced endosperm development. These six have breakpoints that are the most proximal of the set and constitute a graded series with those broken nearer the centromere which have the most abnormal phenotypes. The group of six defines three major regions that produce the endosperm effects. The remaining 32 translocations reduce kernel size very slightly, suggesting the presence of a fourth region distal to all break-points.-The affected class of kernels lacks a paternally derived representative of that segment of 10L translocated to the B centromeric element (B(10) chromosome; 10 10 B(10)). An accompanying class of kernel in which the paternal B(10) chromosome is duplicated in the endosperm (10 10 10(B) B(10) B(10)) is normal. Kernels of the same endosperm constitution synthesized by introducing both 10 and B(10) maternally, however, are defective, resembling 10 10 10(B). Maternal B(10)'s are therefore unable to compensate for the absence of a paternal B(10). Clearly expression of the 10L genes involved supports normal endosperm growth only following pollen transmission.

Two new B-10 translocations involved in the control of nondisjunction of the B chromosome in maize.

A B-A translocation, TB-10(18), has been established involving breakpoints in the proximal region of the long arm of chromosome 10 and the minute short arm of the maize B chromosome. TB-10(18) differs in its nondisjunctional behavior at the second microspore division from TB-10(19), which has a breakpoint in the same region of 10 but in the heterochromatic region of the long arm of B, in the following ways: (1) Nondisjunction of the B(10) chromosome of the TB-10(18) translocation occurs in the absence of the reciprocal element (10(B)), albeit at low frequency. (2) Presence of 10(B) increases the frequency of B(10) nondisjunction but not to the level found for TB-10(19) and certain other translocations. (3) The frequency of B(10) nondisjunction varies among closely related sublines both when 10(B) is present and when it is absent. It is inferred that the B(10) of TB-10(18) carries all the components of B necessary for nondisjunction but that expression is weak in the absence of 10(B), suggesting the existence in the B chromosome short arm of a factor influencing efficient nondisjunction.

Regional control of nondisjunction of the B chromosome in maize.

Control of nondisjunction in the maize B chromosome was studied using a set of B-10 translocations. The study focused on the possible effect of the proximal region of the B long arm. The experimental procedure utilized a combination of a 10(B) chromosome from one translocation with a B(10) from another translocation. The breakpoints of the two translocations were so located that combination of the two elements created a deletion in the proximal region of the B chromosome, but no deletion in chromosome 10. Two different types of deletions were established; one involved a portion of the euchromatic region and the other the entire heterochromatic portion comprising the distal half of the B long arm, except for the small euchromatic tip. Deletion of the heterochromatic portion did not exert any effect on nondisjunction. Deletions of different portions of the euchromatic region produce different responses. Some deletions resulted in typical B nondisjunctional activity; others resulted in the disappearance of this activity. It is concluded that a region within the euchromatic portion of the chromosome is critical for the nondisjunction of B chromosomes. Among 22 translocations with breakpoints in the euchromatic regions, three were proximal to the critical region, 16 were distal and the position of three others was not determined.

Ploidy barrier to endosperm development in maize.

Maize kernels inheriting the indeterminate gametophyte mutant (ig) on the female side had endosperms that ranged in ploidy level from diploid (2x) to nonaploid (9x). In crosses with diploid males, only kernels of the triploid endosperm class developed normally. Kernels of the tetraploid endosperm class were half-sized but with well-developed embryos that regularly germinated. Kernels of endosperm composition other than triploid or tetraploid were abortive.-Endosperm ploidy level resulting from mating ig/ig x tetraploid Ig similarly was variable. Most endosperms started to degenerate soon after pollination and remained in an arrested state. Hexaploid endosperm was exceptional; it developed normally during the sequence of stages studied and accounted for plump kernels on mature ears. Since such kernels have diploid maternal tissues (pericarp) but triploid embryos, the present finding favors the view that endosperm failure or success in such circumstances is governed by conditions within the endosperm itself.-Whereas tetraploid endosperm consisting of three maternal genomes and one paternal genome is slightly reduced in size but supports viable seed development, that endosperm having two maternal and two paternal chromosome sets was highly defective and conditioned abortion. Thus, development of maize endosperm evidently is affected by the parental source of its sets of chromosomes.

Extra cancellous bone induced by combined prostaglandin E2 and risedronate administration is maintained after their withdrawal in older female rats.

Prostaglandin E2 (PGE2) has been recognized for its marked anabolic effect on bone, but the bone gain is lost after the cessation of PGE2 treatment. In previous studies, we were successful in maintaining the new bone by administering a bisphosphonate after the withdrawal of PGE2 treatment. The objective of this study was to determine the fate of the extra bone induced by a combination with PGE2 and risedronate after discontinuing treatment. Ninety-six 9-month-old virgin female Sprague-Dawley rats were treated with 1 or 5 micrograms of risedronate/kg/twice weekly, 6 mg of PGE2/kg/day alone or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of risedronate/kg/twice weekly for 60 days (day 0) and followed by 60 days without treatment (day 60). We have reported the results from the groups treated for 60 days previously. This report is restricted to the histomorphometric findings on the secondary spongiosa of the proximal tibial metaphysis in the groups after withdrawal for 60 days. We found that the only group that maintained the PGE2 induced new bone after withdrawal was the group treated with 6 mg of PGE2/kg/day plus 5 micrograms of risdronate/kg/twice a week. Withdrawal of this combined treatment depressed bone turnover (bone-based bone formation rate, activation frequency) and bone resorption (percent eroded perimeter). The tissue mechanisms responsible for the protection drew from the previously deposited risedronate.

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats.

The purpose of this study was to determine if human parathyroid hormone-(1-38) (hPTH(1-38)) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses of female rats. The right hindlimbs of 6-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization, the rats were subcutaneously injected with 200 micrograms hPTH(1-38)/kg/day for 15 days (short-term treatment) or 75 days (longer-term treatment). Static bone histomorphometry was performed on the primary spongiosa, and both static and dynamic histomorphometry were performed on the secondary spongiosa of the right proximal tibial metaphyses. Immobilization for 30 days without treatment decreased trabecular bone area, number, and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate in the secondary spongiosa. These changes reached a new steady state thereafter. Treatment with 200 micrograms hPTH(1-38)/kg/day for 15 days, beginning 30 days after immobilization, significantly increased trabecular bone area, thickness, and number in both primary and secondary spongiosa despite continuous immobilization when compared with controls. The short-term PTH treatment (15 days) significantly increased labeling perimeter, mineral apposition rate, and tissue referent-bone formation rate in the secondary spongiosa and stimulated longitudinal bone growth as compared with the controls. Longer PTH treatment (75 days) further increased trabecular bone area, thickness, and number as compared with controls and groups given short-term PTH treatment (15 days). The bone formation indices in the secondary spongiosa of the longer-term treated rats were lower than those of the short-term treated group, but they were still higher than those of controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, and restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of female rats with continuously immobilized right hindlimbs. These results suggest that PTH may be useful in treating disuse-induced osteoporosis in humans.

Prostaglandin E2 (PGE2) and risedronate was superior to PGE2 alone in maintaining newly added bone in the cortical bone site after withdrawal in older intact rats.

The objects of this study were (1) to determine the effects of risedronate (Ris) and prostaglandin E2 (PGE2) alone and in combination, on tibial diaphyses of older intact female rats; and (2) to observe the fate of any extra bone if formed after withdrawal of the treatment. Nine-month-old female Sprague-Dawley rats were treated with 6 mg of PGE2/kg/day, 1 or 5 micrograms of Ris/kg twice a week, or 6 mg of PGE2/kg/day plus 1 or 5 micrograms of Ris/kg twice a week for the first 60 days and followed by vehicle injections for another 60 days. Cross-sections of double fluorescent labeled, undecalcified tibial diaphyses proximal to the tibiofibular junction were processed for histomorphometry. We found that: (1) neither the 1 microgram nor the 5 micrograms of Ris treatment in the 60-day on/60-day off group showed any histomorphometric differences from age-related controls; (2) while the 60 days of PGE2 treatment added extra cortical bone (6%) on the tibial shaft (due to stimulation of periosteal, endocortical, and marrow trabecular bone formation), the new endocortical and most of the new marrow trabecular bone were lost when treatment was withdrawn; however, the new periosteal bone remained; (3) PGE2 with Ris added the same amount of new bone to tibial diaphysis as did PGE2 alone and upon withdrawal, new marrow trabecular bone was lost but new periosteal and endocortical bones were preserved in PGE2 + 1 microgram of Ris on/off group. In contrast, all the new bone was maintained in the PGE2 + 5 micrograms of Ris on/off group; (4) PGE2 + Ris cotreatment failed to block the increase in cortical bone porosity induced by PGE2; and (5) in the PGE2 alone and PGE2 + 1 microgram of Ris on/off groups bone turnover was higher than that in the PGE2 + 5 micrograms of Ris on/off group. These results indicate that on/off treatment with PGE2 and Ris is superior to PGE2 alone in that it forms the same amount of new bone during treatment, but preserves more cortical bone during withdrawal. Depression of bone resorption and turnover were the tissue mechanisms responsible for this protection.

Prostaglandin E2 alleviates cyclosporin A-induced bone loss in the rat.

Cyclosporine A (CsA) administered to the male and female rat produces high-turnover osteopenia. Prostaglandins have both bone-resorbing and bone-forming properties, but administration of prostaglandin E2 (PGE2) to the rat in vivo produces a net increase in cancellous bone. To investigate the effects of PGE2 on CsA-induced alteration in bone mass, 43 male Sprague-Dawley rats (9 weeks old) were administered 15 mg/kg of CsA by oral gavage and/or 6 mg/kg of PGE2 by subcutaneous injection daily for 21 days according to the following protocol: group A was an age-matched control; group B received CsA only; group C received PGE2 only; and group D received CsA and PGE2. Serum was assayed on days 0, 7, 14, and 21 for bone gla protein (BGP), PTH, and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. A computerized image analysis system was used for bone histomorphometry of the proximal tibial metaphysis after double tetracycline labeling. Compared to control animals (group A), treatment with CsA alone (group B) and PGE2 alone (group C) significantly elevated BGP levels. Combination therapy (group D) resulted in BGP levels that were significantly higher on days 7 and 14 than with either agent alone. 1,25-(OH)2D was significantly elevated in the CsA group only (group B). Therapy with CsA alone (group B) resulted in a significant osteopenia. The concurrent administration of PGE2 with CsA (group D) alleviated the altered bone mass induced by CsA alone by adding a significant amount of additional bone. This report confirms and extends the current knowledge of the different effects of CsA and PGE2 on bone mineral metabolism and demonstrates that PGE2 can alleviate the deleterious effects of CsA on bone.

Prostaglandin E2 prevents bone loss and adds extra bone to immobilized distal femoral metaphysis in female rats.

The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloading)-induced cancellous bone loss. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to right hindlimb immobilization by bandaging and simultaneously treated subcutaneously daily with 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on the cancellous bone using double-fluorescent labeled, 20 micron thick, undecalcified distal femoral metaphysis sections. We found that PGE2 administration not only prevented diuse-induced bone loss, but also added extra bone to disuse cancellous bone in a dose-response manner. PGE2 prevented the disuse-induced osteopenia by stimulating more bone formation than resorption and shortening the period of bone remodeling. It activated woven bone formation, stimulated lamellar bone formation, and increased the eroded bone surface above that caused by disuse alone. While underloading increased the remodeling period (sigma), PGE2 treatment of underloaded bone shortened the time for osteoclastic bone resorption and bone remodeling, and thus reduced the remodeling space. The study shows that PGE2 is a powerful anabolic agent that prevents disuse-induced osteopenia and adds extra bone to these same bones.

Effects of prostaglandin E2 and risedronate administration on cancellous bone in older female rats.

The effects of Prostaglandin E2 (PGE2) and Risedronate (Ris) both separately and in combination (PGE2 + Ris) were studied on the intact aged female rat skeleton to determine whether the combination of PGE2 with an antiresorptive agent is more effective anabolically than PGE2 alone. Nine-month-old Sprague-Dawley rats were injected subcutaneously either with vehicle, 6 mg PGE2/kg per day, 1 or 5 micrograms Ris/kg twice a week, or 6 mg PGE2/kg per day plus 1 or 5 micrograms Ris/kg twice a week (PGE2 + 1 Ris or PGE2 + 5 Ris) for 60 days. After the treatment, we determined the longitudinal bone growth rate, the qualitative appearance of the primary spongiosa (PS), and the static and dynamic bone histomorphometry of the secondary spongiosa (SS) of the proximal tibial metaphysis (PTM) by examining undecalcified longitudinal sections after double-fluorescent labeling. The relative effects of these treatments on longitudinal bone growth were ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = basal > PGE2 > 1 microgram Ris = 5 micrograms Ris = aging. The density of the PS was ranked as follows: PGE2 + 5 Ris > PGE2 + 1 Ris = PGE2 = 5 micrograms Ris = 1 microgram Ris > basal = aging. The increase in density of the PS was the result of stimulated longitudinal growth and the action of bisphosphonate. Bone mass in the SS was ranked as follows: PGE2 + 5 Ris = PGE2 + 1 Ris = PGE2 > 5 micrograms Ris = 1 microgram Ris = aging = basal.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostaglandin E2 restores cancellous bone to immobilized limb and adds bone to overloaded limb in right hindlimb immobilization rats.

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127% to +188%) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Greater bone formation induction occurred in aged than young cancellous bone sites.

We have determined the differences in the effects of continual prostaglandin E2 (PGE2) treatment in aged (non-growing) and young (growing) cancellous bone sites in 7-month-old Sprague-Dawley rats. The sites involved are the aged distal tibial metaphysis (DTM) with a closed epiphysis and the young proximal tibial metaphysis (PTM) with a slow growing, open epiphysis. The study involved rats treated with 0, 1, 3 or 6 mg PGE2/kg/d for 60, 120 and 180 days. Static and dynamic histomorphometry of percent trabecular area, and tissue-referent bone formation rate (BFR/TV) were determined in both DTM and PTM. In pretreatment controls, the secondary spongiosa of the two metaphyses contain the same amount of cancellous bone (11% in DTM vs. 13% in PTM), but markedly less bone formation in DTM (0.6%/y in DTM vs. 41.5%/y in PTM). After 60 days of 6 mg PGE2/kg/d treatment, %Tb.Ar was increased 607% in DTM and 199% in PTM, BFR/TV was increased to nearly 14 fold in DTM and only 5 fold in PTM. These results indicated the aged metaphysis of the DTM was much more responsive to PGE2 treatment than young, growing metaphysis of the PTM. The results of 120 and 180 days treatment did not significantly differ from 60 days treatment in both sites, indicating that the effect of continuous daily PGE2 treatment were in equilibrium after 60 days. We concluded that aged metaphysis was much more responsive to PGE2 treatment than young growing metaphysis.

Experimental studies on combinations of pyronaridine/primaquine versus chloroquine/primaquine.

The toxicity of combined use of blood schizontocide pyronaridine (PND) and primaquine (PQ) in mice and rats was significantly lower than that of chloroquine (CQ) plus primaquine (PQ). PND 1/2 LD50 (ca 600 mg/kg) in combination with PQ reduced the toxic action of PQ in mice, while CQ 1/2 LD50 (ca 300 mg/kg) plus PQ produced synergistic toxic effect. In animal models such as Plasmodium yoelii sporozoite infection in mice and P. cynomolgi sporozoite infection in rhesus monkeys, the tissue schizontocidal action of PQ was not affected by PND. Therefore, clinical evaluation of PND/PQ in comparison with CQ/PQ in treating vivax malaria is suggested.

The endocrine mechanism of sex reversal in the protandrous black porgy, Acanthopagrus schlegeli: a review.

Black porgy, Acanthopagrus schlegeli Bleeker, a marine protandrous hermaphrodite, is a functional male for the first 2 years of life but begin to sexually reverse to female after the third year. This sex pattern provides a very good model to study the mechanism of sex reversal in fish. The gonad at 5 month of age consisted of testicular tissue with few primary oocytes at 5 month of age. The ovarian tissue became dominant at 18 months of age during the non-spawning season. Testicular and ovarian tissues were separated by connective tissue. Plasma estradiol-17 beta(E2), vitellogenin and 11-ketotestosterone (11-KT) profiles in males were significantly different from those in the 3-year-old reversing females. Peak levels of plasma E2 in the reversing females occurred during the early prespawning season (in October). Lower levels of plasma E2 were, however, observed in the males. Plasma 11-KT levels significant decreased but no changes of plasma testosterone were detected in the reversing females. Exogenous E2 suppressed the testicular development but induced the gonadal aromatase activity, ovarian development and sex reversal in 2-year-old black porgy. Exogenous T and LHRH analog did not have effects on the sex reversal. Higher concentrations of pituitary GtH II and mRNA of GtH II-beta subunit were detected in the reversed females. These data suggested that E2 and gonadal aromatase closely associated to the occurrence of sex reversal. A working model of the sex reversal in black porgy is proposed.

[Ultrasound-guided percutaneous fine-needle puncture cytology in the diagnosis of malignant tumors of the liver].

Results of ultrasound guided percutaneous fine-needle puncture cytology in 142 cases of malignant tumors of the liver are reported. The positive cytology was noted in 118 (83.1%) (10 suspicious). The primary liver cancer comprised 99 cases. In 7 lesions, equal to or less than 3 cm in diameters, 6 were positive in cytology. In 20,3-5 cm in size, 18 were positive. In 15 false-negatives, 12 were larger than 5 cm in diameter. Among 43 cases of metastatic liver cancer, 34 showed positive cytology and 9 false-negative. Among 108 cases of benign hepatic diseases, in 49.1%, it was difficult to arrive at definitive diagnosis by ultrasonography only, but in 97.2% malignancy was excluded by ultrasound guided fine-needle puncture cytology. The suspicious false-positive result occurred only in 3 cases. In this series, there were 250 cases of malignant tumors and benign diseases. The overall accurate diagnostic rate was 89.2%. All the patients had been followed for more than 6 months. The differential diagnosis between malignant and benign tumors, causes of misdiagnosis and complications are discussed.

[Quantitative study on the effect of osthole on proximal tibiae in ovariectomized (OVX) rats].

Thirty-one 3-month-old Female Sprague-Dawley rats were randomly divided into 5 groups, basal control (group 1, killed at the begining), aging control (group 2), ovariectomized (OVX, group 3), OVX with nilestriol treatment group (group 4) and OVX with osthole treatment group (group 5). Group 2 and group 3 ig with water 5 ml.kg-1 and group 5 ig with osthole 6.7 mg.kg-1, all once a day for 6 d; group 4 ig with nilestriol 1 mg.kg-1, once a week. After 12 weeks, all rats were killed. The proximal tibiae of rats were processed to undecalcified sections at 20 microns thickness for histomorphometric analysis. OVX was shown to reduce markedly the trabecular bone mass (%Tb. Ar-59%) due to increase of bone turnover with the result that bone resorption exceeded bone formation, as compared with aging controls. In contrast, treatment of OVX rats with Osthole and nilestriol increased significantly the trabecular area (increased 68% and 27.1% compared with that of OVX respectively). Our results indicate that osthole and nilestriol treatment provides protection against osteoporosis in OVX rats. The protective mechanism of osthole and nilestriol involves supression of bone turnover, but the effects of osthole is lower than that of nilestriol (trabecular area decreased 55% more in osthole group than that with nilestriol treatment). Our finding may provide theoretical evidence for the clinical use of osthole or nilestriol for treatment and prevention of osteoporosis.