Short-term memory: the "storage" component of human brain responses predicts recall.

An evoked potential component with a poststimulus peak at about 250 milliseconds is related to the storage of information in short-term memory. This storage component was found in an investigation of brain potentials in relation to a number and letter comparison task. In replications of this experiment at three different light intensities spaced 1.0 log unit apart, the component had essentially the same waveform and pattern of scores. The memory storage interpretation was confirmed in a behavioral experiment that probed short-term memory. Recall was predicted by the magnitude of the storage component.

Alpha and kappa electroencephalogram activity in eyeless subjects.

Several reports have cast doubt on the cerebral origin of alpha and kappa electroencephalogram activity by charging that they are artifacts related to eye activity. Data are cited which eliminate the corneoretinal potential of the eyeball, tremor of the extraocular muscles, eye position, accommodation, and eye flutter as sources of alpha and kappa electroencephalogram activity. A subject with both eyes removed showed normal alpha and kappa electroencephalogram activity. Marked left-right differences in alpha activity were not found in one-eyed subjects whose eyes and extraocular muscles were completely removed on one side.

Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia.

Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observation suggests the location of a gene important in leukaemogenesis. A series of 68 BCLL tumours have been analysed for allele loss using a series of probes from 13q14. Using intragenic polymorphic markers from the retinoblastoma predisposition gene LOH was observed in 25% of tumours including 3/6 showing cytogenetically obvious deletions of the 13q14 region and 3/6 showing translocations involving 13q14. However, three deletions with proximal breakpoints in 13q14 did not show allele loss, demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with structural rearrangements of 13q14 and 75% of tumours with an apparently normal karyotype. 50% of these tumours showed homozygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimum region of overlap for homozygous deletions is approximately 1 Mbp around the D13S25 locus.

Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations.

The increased or inappropriate expression of genes with oncogenic properties through specific chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21-q22 region being most frequently affected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.

Electroretinogram characteristics and the spectral mechanisms of the median ocellus and the lateral eye in Limulus polyphemus.

Electrical responses (ERG) to light flashes of various wavelengths and energies were obtained from the dorsal median ocellus and lateral compound eye of Limulus under dark and chromatic light adaptation. Spectral mechanisms were studied by analyzing (a) response waveforms, e.g. response area, rise, and fall times as functions of amplitude, (b) slopes of amplitude-energy functions, and (c) spectral sensitivity functions obtained by the criterion amplitude method. The data for a single spectral mechanism in the lateral eye are (a) response waveforms independent of wavelength, (b) same slope for response-energy functions at all wavelengths, (c) a spectral sensitivity function with a single maximum near 520 mmicro, and (d) spectral sensitivity invariance in chromatic adaptation experiments. The data for two spectral mechanisms in the median ocellus are (a) two waveform characteristics depending on wavelength, (b) slopes of response-energy functions steeper for short than for long wavelengths, (c) two spectral sensitivity peaks (360 and 530-535 mmicro) when dark-adapted, and (d) selective depression of either spectral sensitivity peak by appropriate chromatic adaptation. The ocellus is 200-320 times more sensitive to UV than to visible light. Both UV and green spectral sensitivity curves agree with Dartnall's nomogram. The hypothesis is favored that the ocellus contains two visual pigments each in a different type of receptor, rather than (a) various absorption bands of a single visual pigment, (b) single visual pigment and a chromatic mask, or (c) fluorescence. With long duration light stimuli a steady-state level followed the transient peak in the ERG from both types of eyes.

PCR analysis of polymorphisms at the D13S25 locus.

Evidence that the D13S25 locus lies close to a potential tumour suppressor gene implicated in the pathogenesis of B-CLL has been based on detection of LOH and bi-allelic loss using the pH2-42 probe. The SspI polymorphism detected by this probe has been identified by sequencing adjacent clones and a polymorphic (TA)n repeat has been found. Amplification of the region encompassing both polymorphic markers by PCR increases the informativity to 80%.

Effect of cytotoxic therapy on sexuality and gonadal function.

Many chemotherapeutic agents have been shown to cause variable degrees of gonadal dysfunction in both sexes and in all age groups. The severity of the dysfunction depends on the total drug dose and the age at time of therapy. In general, cytotoxic agents produce gonadal dysfunction in men while they produce premature gonadal failure in women. Men develop azoospermia and compensated Leydig-cell function; women sustain ovarian damage causing impaired fertility in the short term and early ovarian failure later. This dysfunction is associated with sexual and emotional difficulties in many patients. In order to discover these problems the physician must sympathetically ask patients and families about their sexual and emotional health. Endocrine and psychologic evaluation help the physician identify the problem. Appropriate counseling and hormone replacement therapy may ameliorate most symptoms and help the patient emotionally adjust to illness and infertility. Prevention of gonadal damage during cytotoxic therapy may be possible in the future. For those young people who retain fertility after cytotoxic therapy, prognosis should be taken into account when counseling about parenthood is given. There is no evidence of genetic abnormalities in the offspring of people previously treated with chemotherapy or irradiation.

Testicular dysfunction in untreated Hodgkin's disease.

Gonadal function was examined in 19 young men with Hodgkin's disease before therapy and compared with that of 11 men with other malignancies, 13 men with primary testicular failure, and 19 normal men of similar age. Total (p less than 0.01) and free (p less than 0.05) testosterone levels were decreased in Hodgkin's disease. In those with advanced (stage III + IV) and symptomatic (B), Hodgkin's disease serum testosterone levels were indistinguishable from those in primary testicular failure, yet serum levels of luteinizing hormone were normal. Moreover, the acute response of serum testosterone to exogenous human chorionic gonadotropin (HCG) was significantly greater in Hodgkin's disease than in primary testicular failure (p less than 0.03). These data and the finding that basal serum follicle-stimulating hormone levels are significantly lower than normal in Hodgkin's disease (p less than 0.05) suggest that the cause of pretreatment hypogonadism in Hodgkin's disease is not simple primary testicular failure. Total sperm count was decreased in 40 percent of men with Hodgkin's disease but in none of the men with other malignancies (p less than 0.05), suggesting specific seminiferous tubular dysfunction in Hodgkin's disease. However, motility was abnormal in 69 percent of men with Hodgkin's disease and 60 percent of those with other malignancies, suggesting that this is a nonspecific effect of cancer. Serum prolactin levels were significantly higher than normal in Hodgkin's disease (p less than 0.05) but not in other malignancies. Our findings suggests that the cause of testicular dysfunction that is present before treatment of Hodgkin's disease is complex, perhaps involving both pituitary and gonadal abnormalities.

Evaluation of a new effect-site controlled, patient-maintained sedation system in dental patients.

We have designed a new effect-site controlled, patient-maintained sedation system for delivering propofol. In the previous systems we developed, the patients retained the use of the handset throughout the procedure and were able to increase the level of sedation. However, it was found that this could potentially lead to oversedation. In the present system, the patients were able to increase their level of sedation until a level was reached that was judged by the patients as being adequate to allow them to tolerate the injection of dental local anaesthetic. The handset was then taken from the patients and the effect site concentration of propofol was maintained at that level for the remainder of the procedure. To assess its safety and efficacy, the system was used to sedate 40 patients presenting for dental procedures under sedation. The system was used successfully and treatment was completed in 39 patients. The system was found to be safe. Both surgeon and patient approval scores were high. Although this study demonstrates the efficacy of effect-site controlled, patient-maintained propofol sedation in this group of patients, further work is required to confirm its safety.

Gonadal injury resulting from chemotherapy.

Radiation, alkylating agents and the vinca alkaloids produce variable degrees of gonadal dysfunction in humans; additional drugs have been linked to gonadal damage in males only. Age at time of exposure and total dose of drug administered are associated with the degree of gonadal injury. Irreversible sterility develops at lower doses in men than in women. The infertile men usually retain sexual function, whereas the infertile women experience premature menopause and sexual dysfunction. Subfertility with normal sexual function is the sequela of lesser degrees of gonadal injury in men and women. For a given drug dose, children apparently sustain less gonadal damage than their adult counterparts. Rigorous reporting of basic essential data will enhance our understanding of drug-induced gonadal damage; incomplete reports only cloud the issue.

EP component identification and measurement by principal components analysis.

Between the acquisition of Evoked Potential (EP) data and their interpretation lies a major problem: What to measure? An approach to this kind of problem is outlined here in terms of Principal Components Analysis (PCA). An important second theme is that experimental manipulation is important to functional interpretation. It would be desirable to have a system of EP measurement with the following characteristics: (1) represent the data in a concise, parsimonous way; (2) determine EP components from the data without assuming in advance any particular waveforms for the components; (3) extract components which are independent of each other; (4) measure the amounts (contributions) of various components in observed EPs; (5) use measures that have greater reliability than measures at any single time point or peak; and (6) identify and measure components that overlap in time. PCA has these desirable characteristics. Simulations are illustrated. PCA's beauty also has some warts that are discussed. In addition to discussing the usual two-mode model of PCA, an extension of PCA to a three-mode model is described that provides separate parameters for (1) waveforms over time, (2) coefficients for spatial distribution, and (3) scores telling the amount of each component in each EP. PCA is compared with more traditional approaches. Some biophysical considerations are briefly discussed. Choices to be made in applying PCA are considered. Other issues include misallocation of variance, overlapping components, validation, and latency changes.

Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease.

It has been reported by us and by others that after chemotherapy for Hodgkin's disease the ovary contains fewer than 5 primordial and primary follicles per 5 x 5 mm biopsy section. In young women this is associated with premature menopause. We report here that before treatment the tissue contains 18--55 such follicles per biopsy section. When women took combination oral contraceptives throughout the course of MVPP therapy, the posttreatment ovarian biopsy tissue had more than 20 follicles per histologic section. Normal menses were established in the five women who discontinued oral contraceptives at the end of MVPP therapy, and one of them is now pregnant.

PIP: The study objective was to determine if suppression of ovarian function by oral contraceptives (OCs) would provide protection against ovarian cell death secondary to chemotherapy. By means of menstrual history, serum gonadotropin levels, and ovarian biopsy, ovarian function was evaluated in 6 young women with untreated Hodgkin's disease. The women ranged in age from 18 to 31 years at onset of treatment. Each woman was given a standard 6 cycles of MVPP therapy (nitrogen mustard, vinblastine, procarbazine, and prednisone). At the time of initiation of MVPP therapy, they were placed on the combination OCs Norlestrin or Ovran on the usual schedule for birth control. 6-12 weeks after the last cycle, 3 women were biopsied and the menstrual history was repeated in all cases. This followup was repeated at intervals of 4-12 months, the most recent in April 1981, range 20-29 months, median 26 months. 5 ovarian biopsies obtained prior to therapy contained 18-55 primordial and primary follicles. Posttherapy ovarian biopsies were performed on 3 of the 6 women who had been treated with OC while they were receiving the 6 cycles of MVPP therapy. The ovary specimens revealed 22, 1000, and 22 primordial and primary follicles per section. Normal menses were established in the 5 women who discontinued OCs at the end of MVPP therapy, and 1 of them is currently pregnant. The pregnancy and the regular menses in the 3 women not on hormonal agents up to 2 years after stopping MVPP therapy encourages the belief that these women will not experience premature menopause in a few years' time. Particularly hopeful is the normal ovarian function of the 30-year-old woman, the woman who was at greatest risk for chemotherapy-induced ovarian failure.

A simple method for 3-dimensional localization of epileptic activity recorded by simultaneous EEG and MEG.

A simple method is presented to average target patterns in the magnetoencephalographic trace of epileptic activity by finding markers in an EEG channel. This method proves to be useful even in cases of low magnetic signal-to-noise ratio. After simultaneously recording electric and magnetic activity the user chooses in the electric trace a template of interest and determines within the same trace all the time points at which the EEG pattern is highly correlated with the chosen template. The magnetic trace portions recorded at those times are averaged together, extracting in this way the magnetic signal from the noise. The MEG results are applied to localize in the brain the active sources that contribute to the recorded signals.