Inhibin and age in men

OBJECTIVE: Normal elderly men are reported to have decreased testicular function despite elevated gonadotrophin levels. We wished therefore to determine if changes in testicular function occur over the age range 19-60 years. DESIGN: Single fasting blood samples were obtained between 0800 and 0900 h. PATIENTS: Working men in a large industrial company between the ages of 19 and 60 years participated in the study. MEASUREMENTS: FSH, serum immunoreactive inhibin and total testosterone were measured, the latter two as measurements of Sertoli and Leydig cell function respectively. RESULTS: The mean baseline serum immunoreactive inhibin level was significantly lower in men from the older age groups, 31-40 years (479 U/l), 41-50 years (439 U/l) and 51-60 years (415 U/l) than in men from the youngest age group, 21-30 years (613 U/l) while serum FSH was higher in men from the older age groups, 41-50 years (3.7 IU/l) and 51-60 years (6.1 IU/l) than in men from the youngest age group, 21-30 years (2.6 IU/l). There appears to be a change in both FSH and inhibin production, consistent with a primary decline in testicular function. There was no significant difference in testosterone levels between the older age group, age 51-60 years and the younger age group, age 21-30 years. However, testosterone levels were significantly lower in the 41-50 year age group, when compared with the 21-30 year, this significance levelling out at about age 45 years. CONCLUSION: The data are consistent with the hypothesis that immunoreactive inhibin reflects inhibin bioactivity, and that inhibin plays a role in the feedback control of FSH secretion in men.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

PERFORATED PEPTIC ULCER IN THE HUNTER REGION: A REVIEW OF 174 CASES

A review of 174 consecutive patients admitted with a diagnosis of perforated peptic ulcer to eight Hunter Region hospitals during 1979–86 is presented. Among the female admissions, the proportion of patients > 70 years of age was twice that in males. One-third of all perforations were in females who accounted for two-thirds of all perforated gastric ulcers. Multivariate analysis revealed that perforations located in the stomach and older age were both significant independent variables adversely affecting outcome following surgery. In contrast, shock at presentation and delay in operating were not statistically significant independent risk factors.     

Mitochondrial DNA variability detected in a single wheat regenerant involves a rare recombination event across a short repeat

The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bb DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements.     

Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.     

Diagnosis of fetal hydronephrosis in utero using ultrasound

Detection of fetal hydronephrosis in utero, subsequent investigation, and surgical treatment is described. With the increasing use of ultrasound for obstetrical problems and greater experience with fetal sonography, more urologic abnormalities will be diagnosed prenatally.