Fetal transplants in rat hippocampus following kainic acid lesions: influence of post-lesion delay on graft survival and integration

Host brain receptivity to fetal hippocampal grafts was investigated following transplantation into unilateral kainic acid (KA) lesions of adult rat hippocampus. E18-E19 hippocampal cell suspensions were labeled with rhodamine dextran amine and transplanted bilaterally into hosts at various times following the KA-lesion. After one to three and one half months survival the grafts (contained within host hippocampal slices) were analyzed using intracellular electrophysiological techniques. A nonparametric graft index was developed which assessed the overall size and distribution of the graft. Using this grading system graft development was noted to be significantly enhanced for grafts placed into hosts with KA lesions at either 2-4 days or 11-12 days following the lesion, compared to grafts placed at either 6-7 days or 27-33 days after the lesion. Also, grafts implanted at delays of either 14-16 or 28-33 days appeared to have fewer surviving cells but were more dispersed within the host brain than grafts at shorter post-lesion implant times. Synaptic responses to host stimulation were noted in most grafts. Intracellular staining of transplanted neurons showed considerable development of cell processes but atypical pyramidal cell morphology and ectopic location; numerous axons traveled into the host tissue. The time course of lesion-induced host receptivity appeared to significantly influence graft development and maturation. In this study graft survival was partially independent from cell migration. This differential effect may be due to various aspects of host brain receptivity, which in turn is influenced by the delay between the host brain lesion and grafting.     

Homosexuality,type 1: An Xq28 phenomenon

Despite the absence of phenotypic manifestations in alternating generations characteristic of X-linked disorders, a thesis is presented that a major type of Kinsey grades 5 and 6 male homosexuality is determined by a gene in the Xq28 region. A total of 133 families in 78 kinships of male and female homosexual probands, in addition to 116 families (including those of 40 famous homosexuals) from the literature, revealed an unbalanced secondary sex ratio in the maternal generation of male, but not of female, homosexuals. On the maternal side, in this study, the ratio of all uncles to all aunts of 90 males homosexuals was 132/209, ² = 8.52, p = 0.004. On the maternal side for the total of all sources, the ratio of uncles to aunts of male homosexuals was 241/367, ² = 13.20; p < 0.0001. The male/female ratio of the total number of maternal sibships bearing homosexuals (310/628: 0.491) was a measure of fetal wastage of the mothers' male sibs: 49%. This ratio was very close to that of the total number of children born to fathers affected with any one of nine Xq28-linked male semilethal conditions (255/508: ratio 0.556); for the difference between the two populations ² = 0.859, p = 0.354. The male/female ratio of the total number of children born to female carriers of any one of these same conditions (1,232/1,062: ratio 1.16), ² = 13.8 p 0.0001, is close to that of the total number of children in homosexual sibships: 511/413, ² = 10.4, p = 0.005. Between the number of children born to Xq28 mothers and to those born of mothers of homosexuals ² = 0.581, p = 0.446. One may readily surmise that the maternal influence so often related to homosexuality may lie in the mother being a genetic carrier, with traits thereto associated. In this study, 65% of the mothers of homosexuals had no or only one live-born brother. Additional support for a genetic hypothesis is found in the occurrence of multiple instances—almost exclusively among maternal relatives—of infertility, spontaneous abortions, miscarriages, stillbirths, remaining single past age 30, and suicide. Of 109 male and 43 female homosexual index cases in the present series there were 6 instances of brother/sister homosexual sibships. Instances of homosexual parent-to-homosexual child transmission occurred as follows: one father-to-son; one father-to-daughter; one bisexual father-son; one father/mother-to-2 sons; one of mother-to-son, and one of father-to-son and father-to-bisexual daughter. There were 16 instances of presumptive transmissions from heterosexual father-to-homosexual son and 5 of heterosexual father-to-homosexual daughter. A hypothesis is proposed: Homosexuality is due to a gene at Xq28 characterized by (i) elongated cytosine-containing trinucleotide repeats upstream to translation of a gene, (ii) elongated CpG islands upstream of the trinucleotides, and (iii) cytosine methylation of CpG islands and of the cytosine-containing trinucleotides.A limited number of long tables of data, and pedigree charts, which provide the details from which this paper was developed, may be obtained on paper or on disc from the author or, for a modest fee, from the Librarian, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York 11794.     

Total-body irradiation on an isocentric linear accelerator: a radiation output compensation technique

A treatment technique for total-body irradiation (TBI) is proposed that combines arc therapy with dynamic output control to achieve high-grade dose uniformity. The patient lies on a low couch and receives exposure in the prone and supine positions from a modulated arcing beam. The technique has been validated using a personal computer to control the linear accelerator and we demonstrate that only minor alterations to current dynamic therapy systems would be required. We have examined the practical application of this treatment with emphasis on methods of conformal therapy where an optimized dose distribution is prepared from a matrix of caliper measurements taken from the patient. This technique provides a means for regular TBI treatment on a computer-controlled linear accelerator that is easy to set up, requires short exposure times and is comfortable for the patient.     

What do Irish women know about cervical screening?

In anticipation of the launch of the national cervical screening programme, a questionnaire was distributed amongst 200 women on the maternity wards of the Coombe Women's Hospital. The questionnaires revealed that 24% of the women surveyed never had a smear test and 50% of these did not know how the test was performed. The majority of all women did not know what a smear test showed and 26% did not know the meaning of an abnormal smear. Irish women's knowledge of cervical screening is limited, and the success of the proposed programme will depend on an improvement in public information and education.     

The effects of seasons and light therapy on G protein levels in mononuclear leukocytes of patients with seasonal affective disorder

BACKGROUND: Information-transducing heterotrimeric G proteins have been implicated previously in the mechanism of action of mood stabilizers and in the pathophysiology of mood disorders. Mononuclear leukocytes of patients with unipolar and bipolar depression have been characterized by reduced measures of the stimulatory and inhibitory G proteins. In this study, patients with seasonal affective disorder (SAD) were measured for mononuclear leukocyte G protein levels while depressed during the winter, following light therapy, and in remission during the summer. METHODS: Twenty-six patients with SAD and 28 healthy subjects were assessed in the study. The immunoreactivities of Gs alpha, Gi alpha, and Gbeta subunit proteins were determined by Western blot analysis of mononuclear leukocyte membranes with selective polyclonal antibodies for the various G subunit proteins, followed by densitometric quantitation using an image analysis system. RESULTS: Untreated patients with SAD and winter, atypical-type depression showed significantly reduced mononuclear leukocyte immunoreactive levels of Gs alpha and Gi alpha proteins, similar to previous observations in patients with nonseasonal major depression. The reduced G protein levels were normalized with 2 weeks of light therapy. The same patients while in remission during the summer had G protein levels that were similar to those of healthy subjects. CONCLUSIONS: G protein-immunoreactive measures in patients with SAD are suggested as a state marker for winter depression, which is normalized by light treatment and during the summer. We speculate that light may exert its effects via normalization of transducin (Gt protein) levels, which are thought to be reduced in winter depression.     

Optimal histopathologic examination of the sentinel lymph node for breast carcinoma staging

Sentinel lymph node dissection is a minimally invasive surgical technique for staging of breast carcinoma. The optimal pathologic examination of the sentinel node (SN) has not yet been determined. Our standard protocol for evaluation of the SN in patients with breast cancer included frozen section at one level, plus paraffin sections at two levels, separated by 40 microm, and stained with hematoxylin and eosin and cytokeratin immunohistochemistry (IHC) at each paraffin section level. In the current study, we evaluated the use of step sections and cytokeratin IHC in 60 SNs (42 consecutive patients) that were tumor-negative on frozen section and hematoxylin and eosin staining at permanent section levels 1 and 2. The SN were reexamined with cytokeratin IHC at eight additional levels (levels 3-10) of the paraffin block, each separated by 40 microm. Previous IHC sections from levels 1 and 2 had shown micrometastases in nine SNs (eight patients) and no tumor cells in the remaining 51 SNs (34 patients). Of the 51 previously negative SNs, only two (4%) SNs from one (3%) patient had metastatic carcinoma cells in levels 3-10. Thus, the additional step sections with cytokeratin IHC did not significantly increase the number of patients with tumor-positive SNs. We currently recommend that the SN be examined with cytokeratin IHC at two levels of the paraffin block. This should optimize sentinel lymph node dissection as a staging technique and minimize the labor and financial burden associated with multiple step sections and IHC stains.