The Plasmodium circumsporozoite protein is involved in mosquito salivary gland invasion by sporozoites

Plasmodium sporozoites develop in oocysts on the midgut wall of the mosquito and are released into the hemocoel. Approximately 15-20% of oocyst sporozoites will successfully attach to and invade salivary glands, their target organ. We have previously shown that the major surface protein of sporozoites, the circumsporozoite (CS) protein, binds specifically to salivary glands and not to other mosquito organs exposed to circulating hemolymph. In addition, a peptide from the N-terminal portion of CS protein inhibits binding of the protein to the glands. In this study, we have extended these findings and show that both the protein and the peptide can inhibit sporozoite invasion of salivary glands.     

Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer

A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD.     

Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.     

Persistent genetic isolation in outport Newfoundland

The historical development of genetic isolation has been evaluated for three outport Newfoundland study areas. An attempt was made to ascertain all livebirths in each study area, and determine the parentage of each. Data from records of baptism and marriage were used for this, supplemented with other historical and ethnographic information. Parent-offspring migration was used as a measure of genetic exchange between subpopulations within study areas, and gene flow into the study areas. Currently, 1-8% of parents originate outside the study areas; these rates are low compared to earlier periods, and compared to present-day rates for European isolate populations. Average kinship was estimated, to measure genetic relatedness within and between subpopulations of each area and the potential for random inbreeding; these values, which are minimum estimates, are now at historically high levels. Increased migration into the study areas, which would decrease average kinship, is not likely. Thus, any regionally or locally elevated frequencies of deleterious alleles will persist, and must be taken into account in providing genetic counseling and evaluating the utility of local screening programs.     

Local properties of a functionally graded interphase between cementum and dentin

The study of natural interfaces may provide information necessary to engineer functionally graded biomaterials for bioengineering applications. In this study, the mechanical, structural, and chemical composition variations associated with a region between cementum and dentin were studied with the use of nanoindentation, microindentation, optical microscopy, and Raman microspectroscopy techniques. Three-millimeter-thick transverse sections (N = 5) were obtained from the apical one-third of the roots of sterilized human molars. The samples were ultrasectioned at room temperature with the use of a diamond knife and an ultramicrotome. Longitudinal ground sections of 100 microm thickness were prepared and stained with von Kossa stain to determine the mineralized regions within the molar roots. Raman microspectroscopy was used to determine the relative inorganic content, mainly apatite (PO4(3-)nu1 mode at 960 cm(-1)) and organic content, mainly collagen (C--H stretch at 2940 cm(-1)) between cementum and dentin bulk tissues. The microindentation and nanoindentation results indicated a gradual transition in hardness from cementum to dentin over a width ranging from 100 to 200 microm. However, the variation in hardness data for cementum and dentin by nanoindentation was larger (0.62 +/- 0.21, 0.77 +/- 0.14 GPa) than from microindentation (0.49 +/- 0.03, 0.69 +/- 0.07 GPa). Within the 100 to 200 microm region there was a 10 to 50 microm fibrillar hydrophilic cementum-dentin junction (CDJ) with mechanical properties significantly lower than either the cementum or the dentin side of CDJ. Light microscopy revealed a 100 to 200 microm translucent region between cementum and dentin. Raman microspectroscopy results showed a variation in organic and inorganic composition 80 to 140 microm wide. It was concluded that a morphologically and biomechanically different CDJ lies within a wider cementum-dentin interphase. Hence, cementum, dentin, and the interphase can be classified as a functionally graded dental tissue within the root of a tooth.     

Small effect of brown adipose tissue and major effect of photoperiod on body weight in hamsters (Mesocricetus auratus)

It has been suggested that brown adipose tissue plays a special role in the control of body weight. This hypothesis was investigated by measuring the body weight of female hamsters over a two month period following removal of interscapular brown adipose tissue. Two groups of animals were used, one maintained on a short day (10:14 light: dark ratio) and the other on a long day (16:8 light: dark ratio) photoperiod. Under both photoperiod conditions hamsters with interscapular brown adipose tissue removed gained somewhat more weight than their corresponding sham operated controls. Photoperiod, however, had a much larger effect on body weight. Hamsters maintained on short days increased their body weight by about 60 percent during the two months of the experiment whereas the hamsters maintained on long days increased their body weight by only about 17 percent. It was concluded that brown adipose tissue plays a small non special role in the control of body weight in the female hamster, but that the light-dark ratio is quantitatively much more important under these experimental conditions.     

Lactation and breast cancer. Evidence for a negative association in premenopausal women

The authors report a case-control study of breast cancer based on an analysis of data collected by interview between the years 1957-1965 from women residing in the communities of Buffalo and Kenmore, New York. Prior reproductive factors, including a detailed lactation history, were examined for 453 white females with breast cancer and 1,365 white females without breast cancer who were selected randomly from the population of Buffalo and Kenmore. There is evidence of a negative association between length of nursing and breast cancer risk in premenopausal women which is not seen in the postmenopausal women. This apparent "protective" effect of lactation persists after statistical control for the potential confounding factors of age, parity, age at first pregnancy, age at menarche, and education. Cases are more likely than controls to have reported unsuccessful lactations due to "insufficient milk." The findings of this study, in conjunction with the authors' review of previously published studies that have examined prior lactation as related to breast cancer risk, suggest that there may be an independent negative association between nursing and subsequent breast cancer risk in premenopausal women. Whether this means that breast feeding is protective or that some women who are unsuccessful at lactation are at increased risk for subsequent breast cancer is not clear. A detailed reanalysis of existing data and more careful attention to detailed prior breast function/dysfunction in future studies are recommended.     

A method for studying inhibitory activity in whole urine

Summary A method has been developed for inducing and quantifying calcium oxalate crystallisation in whole human urine. The propensity of a given urine to induce crystal formation was described in two ways: 1) its ability to resist spontaneous nucleation of calcium oxalate crystals was assessed by titrating 20 mls of the urine with increasing quantities of sodium oxalate (0–150 mol) to determine its practical metastable limit. This limit was inversely related to the endogenous calcium concentration. 2) its capacity to inhibit crystal growth was quantified by determining the rate of growth of calcium oxalate crystals precipitated in response to a fixed oxalate load (30 mol) above its metastable limit. The crystals produced were predominantly calcium oxalate dihydrate and were morphologically identical to those occurring naturally in urine. Citrate had no effect on the metastable limits of 3 urines examined, but markedly inhibited crystal growth. Pyrophosphate had a similar effect on crystal growth, and in addition, raised the metastable limit of one of the urine samples.     

Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): Results with a new battery on tests

Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha₂ agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 g/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 g/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha₂ receptors in the action of clonidine.     

Cumulative renal tubular damage associated with cisplatin nephrotoxicity

Summary We assessed the acute and chronic effect of multiple courses of cisplatin therapy on renal tubules by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl--D-glucosaminidase, and total protein. Urine specimens were obtained before and after doses of cisplatin (90 mg/m²) given to 12 patients. Each dose of cisplatin induced transient increases in enzyme excretion, followed by proteinuria 3–5 days later. Transient enzymuria after the last cisplatin dose was significantly greater than that after the first dose. Moreover, persistent increases in urinary N-acetyl--D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage. Our findings disclosed striking differences between patients in susceptibility to progressive nephrotoxicity.Supported by Biomedical Research Support Grant RR05584 (MPG), Cancer Center Support Grant (CORE) CA-21765, Chilhood Solid Tumor Program Project Grant CA-23099 and the American Lebanese Syrian Associated Charities (ALSAC)