Phosphate metabolites and steroid hormone receptors of benign and malignant breast tumors. A Nuclear Magnetic Resonance study

Phosphorous 31 (31P) nuclear magnetic resonance (NMR) spectra were recorded from perchloric acid extracts of benign and malignant breast tumors. The spectra were correlated with the histopathologic diagnosis and the steroid receptor status of the tumor. Higher relative content of the lipid-derived metabolite glycerolphosphoethanolamine (GPE), the high-energy nucleoside phosphates (nucleoside-diphosphate [NDP], nucleoside-triphosphate [NTP]), and sugar esters of uridine diphosphate (UDPS) appeared in the carcinomas. Malignant tumors also showed a lower ratio of phosphoethanolamine to phosphocholine (PE/PC) than benign conditions. Lower content of the lipid-derived metabolite glycerolphosphocholine (GPC) and high content of the high-energy compound phosphocreatine (PCr) were associated with malignant tumors having high content of estrogen receptors (ER). High PCr content was also associated in the carcinomas with high progesterone receptors (PgR) content. In the benign tumors NDP and NTP were higher in tumors with high PgR content. The authors suggest that 31P magnetic resonance spectroscopy (MRS) of the breast can provide additional variables to diagnose malignancy, and when combined with magnetic resonance imaging (MRI), invasive procedures may be avoided. It also seems that levels of PCr and GPC obtained from the spectra can serve as markers to hormonal receptor status of breast carcinomas, and may be used in addition to the ER and PgR content to improve prediction of the response to hormonal therapy. Additional development requires in situ MRI and MRS combined studies.     

Calmodulin inhibitors and 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate do not prevent the inhibitory effect of prostaglandin F2 alpha on cyclic AMP production in isolated rat corpora lutea

In the rat corpus luteum, prostaglandin F2 alpha (PGF2 alpha) rapidly inhibits LH-induced cyclic AMP (cAMP) production when given in vivo or to isolated corpora lutea, but not to broken-cell preparations. The suggestion that increased cytosolic calcium concentration mediates PGF2 alpha action was investigated in corpora lutea of pseudopregnancy induced in immature rats by administration of pregnant mare serum gonadotrophin (15 i.u.). Isolated 10-day-old corpora lutea were incubated for 90 min with LH (5 micrograms/ml), PGF2 alpha (10 mumol/l) and other additions, and cAMP concentration in the tissue was estimated. The putative inhibitor of intracellular calcium release or action, 8-(n,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8; 30 or 150 mumol/l), did not abolish the effect of PGF2 alpha. Similarly ineffective was the combination of TMB-8 (150 mumol/l) and calcium-depleted medium (free ionized calcium concentration, 30 nmol/l). Calmodulin inhibitors of three different chemical structures were then tested. The phenothiazine trifluoperazine, at 300 as well as 30 mumol/l, did not interfere with the inhibitory effect of PGF2 alpha on cAMP, while suppressing (at 300 mumol/l) progesterone secretion in LH-treated tissue. Furthermore, inhibition by PGF2 alpha was not impaired by pimozide, a diphenylbutylpiperidine (25 and 50 mumol/l) nor by N-(6-aminohexyl)-5-chloro-1-naphthalene sulphonamide (W-7; 15 and 45 mumol/l). In the presence of LH alone, W-7 (45 mumol/l) inhibited and TMB-8 (30 mumol/l augmented cAMP accumulation, indicating that the luteal tissue was effectively exposed to these compounds. Thus, drugs known to inhibit calcium- and calmodulin-dependent processes in a variety of tissues did not abolish the inhibitory action of PGF2 alpha on luteal cAMP production.     

The value of curettage in the diagnosis of ectopic pregnancy

The charts of all patients hospitalized between 1978 and 1983 with proved ectopic pregnancies at Northwestern Memorial Hospital, Chicago, and Meir Hospital, Kfar-Sava, Israel, were reviewed. Eighty-four patients with ectopic pregnancies had endometrial tissue available for histologic analyses. Review of the endometrial curettings revealed that the most common endometrium associated with ectopic pregnancy was secretory (39.4%). Proliferative endometrium present 19% of the time was as common a finding as Arias-Stella phenomenon. This study shows that any type of endometrium lacking trophoblasts may be associated with an ectopic pregnancy. The lack of decidual reaction or Arias-Stella phenomenon should not alone lower the clinician's index of suspicion.     

与长寿有关的特殊脂蛋白表型和基因型

背景：长寿个体年龄相关疾病的发病率较低且发病时凤明显后延，其家族成员可能遗传有某些调节衰老过程或疾病敏感性的因子。     

Intracellular survival of persistent group A streptococci in cultured epithelial cells

Group A streptococcus (GAS) is the principle etiologic agent of bacterial pharyngotonsillitis and a wide range of other diseases. Failure to eradicate GAS from patients has been documented in 5-30% of patients with pharyngotonsillitis, in spite of the continued sensitivity of GAS to penicillin and other beta-lactams. It was recently proposed that eradication failure might be attributed to the ability of GAS to maintain an intracellular reservoir during antibiotic treatment. We have previously shown that strains derived from patients with bacterial eradication failure, despite antibiotic treatment (persistent strains), adhered to and were internalized by cultured epithelial cells more efficiently than strains that were successfully eradicated. Since, penicillin and other beta-lactams do not penetrate well into mammalian cells, intracellular survival of GAS is crucial in order to persist during prolonged antibiotic treatment. In this study, we compared the survival of GAS strains from cases of eradication failure and eradication success, using an epithelial cell culture model. We found that persistent strains show significantly increased intracellular survival, compared to the 'eradication success' strains. This finding supports the idea that an intracellular reservoir of GAS plays a role in the etiology of antibiotic eradication failure.     

Natural killer cell activity in post-necrotic cirrhotic patients as related to hepatitis-B virus infection and plasma zinc levels

In view of the suggested physiological role of natural killer (NK) cells in immunosurveillance and defence against viral infections, we have investigated the relationship between hepatitis B virus (HBV) infection and NK activity against K-562 cells in patients with post-necrotic cirrhosis. Overall, the NK activity in cirrhotic patients did not differ from age- and sex-matched controls. However, cirrhotic males with evidence of HBV infection with or without HBs antigenemia tend to have lower NK activity than controls. Cirrhotic males without evidence of HBV infection do not differ from controls. Such a trend was not observed in the female cirrhotic patients examined. In addition significantly reduced NK activity was observed in cirrhotic patients with low plasma zinc levels. This relationship is of interest because of the known association between zinc deficiency and various immunodeficiencies.     

Cyclic nucleotide levels in human breast cancer and in rat mammary tissues during tumor development

The levels of cyclic adenosine 3:5-monophosphate (cAMP) and cyclic guanosine 3:5-monophosphate (cGMP) were studied in dimethylbenz(a)anthracene (DMBA)-induced mammary tumors of Sprague-Dawley rats and in human breast cancer. In the rat carcinomas, these levels were significantly lower than in non-malignant tissues when calculated on the basis of DNA content, but higher (cAMP) or equal (cGMP) when calculated on the basis of weight. In human breast cancer the cyclic nucleotide levels were higher than in non-malignant tissues according to both methods of calculation. No correlation was found in human carcinomas between the cyclic nucleotide levels and mitotic index, nuclear grade, tumor size, or lymph node involvement. The rat tumors were subclassified according to state of differentiation, mitotic index, and state of development. Not all the sub-groups had cAMP levels different from normal values. Differences in cAMP levels between the sub-groups could not be correlated with tumor growth rates and/or mitotic index. Thus, cyclic nucleotides may not be useful in prognosis of breast cancer.     

Noninfectious gas accumulation in an infarcted spleen

BACKGROUND: Intentional selective occlusion of the arterial blood supply to tumors of abdominal organs is a well established therapeutic procedure. Several reports described gas accumulation at the infarcted sites. These gas collections are usually nonsuppurative; however, the differential diagnosis should include abscess formation. CASE REPORT: We present a 59-year-old patient in whom the splenic artery was accidentally ligated during gastrectomy surgery, with resultant splenic infarction. Gas accumulation was diagnosed by sonography and CT studies. To the best of our knowledge this is the first report ever published in the English medical literature describing nonsuppurative gas formation within an abdominal organ, caused by accidental ligation of its main arterial supply during surgery. SUMMARY: Possible theories regarding this noninfectious gas accumulation are discussed and the differential diagnosis between abscess formation and noninfectious gas accumulation is emphasized. Establishing the correct diagnosis is of big clinical importance as the treatment of choice is completely different in each one of these entities although the imaging features, in ultrasound as well as in CT, are somewhat similar.     

Should we treat elevated thyroid stimulating hormone levels in obese children and adolescents?

OBJECTIVE: To examine the prevalence of abnormal thyroid function tests among obese children and adolescents, and to study the effect of thyroid hormone supplementation on body weight, linear growth and lipid profiles in these children. DESIGN: Thyroid function tests and lipid profiles were measured in 196 obese children and adolescents. Thyroid auto-antibodies were measured in children with hyperthyrotropinemia (elevated thyroid stimulating hormone (TSH) and normal free thyroxine-FT4). All children with hyperthyrotropinemia participated in a combined dietary-behavioral-physical activity weight management intervention. Fifteen of the obese children with hyperthyrotropinemia were also treated with thyroid hormone substitution for 6 months and were compared to non-treated subjects (n = 26). RESULTS: Forty-one obese children had hyperthyrotropinemia (20.9%). Positive thyroid auto-antibodies were only found in 19.5% of these children. Treatment had no significant effect on body weight, linear growth and lipid profile, except for causing a greater decrease in triglyceride levels. TSH levels returned to normal ranges in the majority of children with hyperthyrotropinemia who participated in the combined intervention, irrespective of thyroxine treatment. CONCLUSIONS: Hyperthyrotropinemia is relatively common in obese children, but autoimmune thyroid disease accounts for a minority of the cases. TSH levels returned to normal in the majority of patients even without thyroid hormone administration. No beneficial effects on body weight, body mass index, linear growth and body lipids were found in treated subjects, suggesting that thyroid substitution is not necessary in most cases.