Search PubMed⌕ Search

Biomedical subjects

J Hertz

Publications and source records attributed to J Hertz.

At least 19 recordsLinked to original sources

Random heteropolymer dynamics.

We study the Langevin dynamics of the standard random heteropolymer model by mapping the problem to a supersymmetric field theory using the Martin-Siggia-Rose formalism. The resulting model is solved nonperturbatively employing a Gaussian variational approach. In constructing the solution, we assume that the chain is very long and impose the translational invariance which is expected to be present in the bulk of the globule by averaging over the center of mass coordinate. In this way we derive equations of motion for the correlation and response functions C(t,t') and R(t,t'). The order parameters are extracted from the asymptotic behavior of these functions. We find a dynamical phase diagram with frozen (glassy) and melted (ergodic) phases. In the glassy phase the system fails to reach equilibrium and exhibits aging of the type found in p-spin glasses. Within the approximations used in this study, the random heteropolymer model can be mapped to the problem of a manifold in a random potential with power law correlations.

Journal Article↗

Modeling genetic regulatory dynamics in neural development.

We model genetic regulatory networks in the framework of continuous-time recurrent networks. The network parameters are determined from gene expression level time series data using genetic algorithms. We have applied the method to expression data from the development of rat central nervous system, where the active genes cluster into four groups, within which the temporal expression patterns are similar. The data permit us to identify approximately the interactions between these groups of genes. We find that generally a single time series is of limited value in determining the interactions in the network, but multiple time series collected in related tissues or under treatment with different drugs can fix their values much more precisely.

Algorithms↗

Foreign DNA integration--perturbations of the genome--oncogenesis.

We have been interested in the consequences of foreign DNA insertion into established mammalian genomes and have initially studied this problem in adenovirus type 12 (Ad12)-transformed cells or in Ad12-induced hamster tumors. Since integrates are frequently methylated de novo, it appears that they might be modified by an ancient defense mechanism against foreign DNA. In cells transgenic for the DNA of Ad12 or for the DNA of bacteriophage lambda, changes in cellular methylation and transcription patterns have been observed. Thus, the insertion of foreign DNA can have important functional consequences that are not limited to the site of foreign DNA insertion. These findings appear to be relevant also for tumor biology and for the interpretation of data derived from experiments with transgenic organisms. For most animals, the main portal of entry for foreign DNA is the gastrointestinal tract. Large amounts of foreign DNA are regularly ingested with the supply of nutrients. Starting in 1987/1988, we have been investigating the fate of orally administered foreign DNA in mice. Naked DNA of bacteriophage M13 and the cloned gene for the green fluorescent protein (GFP) of Aequorea victoria have been used as test molecules. Moreover, the plant-specific gene for the ribulose-1,5-bisphosphate carboxylase (rubisco) has been followed in mice after feeding soybean leaves. At least transiently, food-ingested DNA can be traced to different organs and, after transplacental transfer, to fetuses and newborns. There is no evidence for germ line transmission or for the expression of orally administered GFP DNA.

Adenoviridae↗

Epigenetic and genotype-specific effects on the stability of de novo imposed methylation patterns in transgenic mice.

The chloramphenicol acetyltransferase gene under the control of the late E2A promoter of adenovirus type 2 (Ad2) was introduced as transgene into the B6D2F1 mouse strain with mixed genetic background and became extensively de novo methylated. The methylation of this pAd2E2AL-CAT (7-1A) transgene was regulated in a strain-specific manner apparently depending on the site of integration. Transmission of the 7-1A transgene into an inbred DBA/2, 129/sv, or FVB/N genetic background led to a significant loss of methylation in the transgene, whereas C57BL/6, CB20, and Balb/c backgrounds favored the de novo methylation in very specific patterns. The newly established patterns of de novo methylation were transmitted to the offspring and remained stable for many generations, regardless of the heterozygosity of strain-specific DNA sequences present in these mouse strains. Segregation analyses showed a non-mendelian transmission of methylation phenotypes and suggested the involvement of dominant modifiers of methylation. The genotype-specific modifications of the transgene were followed for 11 backcross generations. These observations reflect an evolutionarily conserved mechanism directed against foreign, e.g. viral or bacterial, DNA at least in the chromosomal location of the 7-1A transgene. In seven additional mouse lines carrying the same transgene in different chromosomal locations, strain-specific alterations of methylation patterns were not observed.

Animals↗

Coarse-grained reverse engineering of genetic regulatory networks.

We have modeled genetic regulatory networks in the framework of continuous-time recurrent neural networks. A method for determining the parameters of such networks, given expression level time series data, is introduced and evaluated using artificial data. The method is also applied to a set of actual expression data from the development of rat central nervous system.

Algorithms↗

Odour recognition and segmentation by a model olfactory bulb and cortex.

We present a model of an olfactory system that performs odour segmentation. Based on the anatomy and physiology of natural olfactory systems, it consists of a pair of coupled modules, bulb and cortex. The bulb encodes the odour inputs as oscillating patterns. The cortex functions as an associative memory: when the input from the bulb matches a pattern stored in the connections between its units, the cortical units resonate in an oscillatory pattern characteristic of that odour. Further circuitry transforms this oscillatory signal to a slowly varying feedback to the bulb. This feedback implements olfactory segmentation by suppressing the bulbar response to the pre-existing odour, thereby allowing subsequent odours to be singled out for recognition.

Afferent Pathways↗

Transvaginal sonohysterography and hysteroscopy in the evaluation of female infertility, habitual abortion or metrorrhagia. A comparative study.

BACKGROUND: To assess the diagnostic value of sonohysterography in the evaluation of metrorrhagia and infertility with hysteroscopy as the standard. METHODS: Sixty-six women, 41 with metrorrhagia, 20 with infertility and five with habitual abortion, were examined by sonohysterography and hysteroscopy. Sterile saline instilled through a baby-feeding tube was used to distend the uterine cavity during sonohysterography. Hysteroscopy was performed with a 4 mm hysteroscope under general anesthesia. The endometrial polyps and submucous myomas were recorded and the findings subsequently compared. RESULTS: Of the 66 women, 60 were successfully examined by both sonohysterography and hysteroscopy. The overall sensitivity and specificity for sonohysterography was 90.9% and 100%, respectively. The positive and negative predictive values were 100% and 90%, respectively. When examining the metrorrhagia and infertility groups separately the sensitivity and specificity and predictive values were found to be 88.5%, 100%, 100% and 76.9% (metrorrhagia) and 100% for all parameters in cases of infertility. No complications were recorded during the procedures. CONCLUSION: Sonohysterography is a simple, fast, well tolerated and accurate method to evaluate the uterine cavity in patients with metrorrhagia or infertility.

Abortion, Habitual↗

Prevalence of carcinoma in situ of the testis in 207 oligozoospermic men from infertile couples: prospective study of testicular biopsies.

OBJECTIVE: To investigate the prevalence of carcinoma in situ of the testis in a group of oligozoospermic men from infertile couples. DESIGN: A consecutive group of oligozoospermic men from infertile couples were offered bilateral testicular biopsy. The observed prevalence of carcinoma in situ was compared with the expected prevalence of testicular cancer in a corresponding age matched population of Danish men, assuming all untreated cases of carcinoma in situ progress to tumour stage. This calculation was based on data from the Danish Cancer Registry. SUBJECTS: 207 men aged 18-50 years who had sperm density below 10 million/ml in two samples within the previous 2 years or sperm density below 20 million/ml in two samples within the previous 2 years and a history of cryptorchidism or one or two atrophic testicles (orchidometer volume less than 15 cm3), or both. INTERVENTIONS: Bilateral testicular biopsies. MAIN OUTCOME MEASURES: Carcinoma in situ in the biopsy specimen. RESULTS: No case of carcinoma in situ was found among the 207 men. The expected number in a normal age matched population of corresponding size was 0.8. CONCLUSIONS: There is no increase in risk of carcinoma in situ of the testis in moderately oligozoospermic men of couples referred because of infertility.

Adolescent↗

How well can we estimate the information carried in neuronal responses from limited samples?

It is difficult to extract the information carried by neuronal responses about a set of stimuli because limited data samples result in biased estimates. Recently two improved procedures have been developed to calculate information from experimental results: a binning-and-correcting procedure and a neural network procedure. We have used data produced from a model of the spatiotemporal receptive fields of parvocellular and magnocellular lateral geniculate neurons to study the performance of these methods as a function of the number of trials used. Both procedures yield accurate results for one-dimensional neuronal codes. They can also be used to produce a reasonable estimate of the extra information in a three-dimensional code, in this instance, within 0.05-0.1 bit of the asymptotically calculated value--about 10% of the total transmitted information. We believe that this performance is much more accurate than previous procedures.

Computer Simulation↗

Pyloric exclusion in the management of duodenal trauma: is concomitant gastrojejunostomy necessary?

Pyloric exclusion with gastrojejunostomy (PE-GJ) has been recommended in patients with severe injuries to the pancreatoduodenal complex. Recently, the management philosophy for pancreatoduodenal injuries has been that less treatment is probably the best treatment. But whether gastrojejunostomy (GJ) should be used routinely with pyloric exclusion (PE) remains controversial. A retrospective review was conducted of patients who underwent PE at a Level I trauma center during a 36-month period. Forty-five patients had duodenal injuries and 12 of these (27%) underwent PE for management of complex duodenal injuries. Gunshot wounds were the cause of the injuries in 10 of the 12 patients (83%). Eight patients (67%) underwent PE-GJ and had a mean hospital stay of 25 days. Four patients (33%) underwent PE alone and had a mean hospital stay of 29 days. All 12 patients had spontaneous opening of the PE, regardless of the technique used. One patient (12.5%) in the PE-GJ group developed marginal ulceration and significant hemorrhage, and one patient died in the PE-GJ group. The reported incidence of marginal ulceration in the PE-GJ group, the spontaneous opening of the pylorus, and the need to limit the extent of surgical repair to focus on all other associated lesions present in these patients, suggest that GJ should not be used routinely in patients undergoing PE for the management of severe pancreatoduodenal injuries.

Adult↗

Learning synfire chains: turning noise into signal.

We develop a model of cortical coding of stimuli by the sequences of activation patterns that they ignite in an initially random network. Hebbian learning then stabilizes these sequences, making them attractors of the dynamics. There is a competition between the capacity of the network and the stability of the sequences; for small stability parameter epsilon (the strength of the mean stabilizing PSP in the neurons in a learned sequence) the capacity is proportional to 1/epsilon 2. For epsilon of the order of or less than the PSPs of the untrained network, the capacity exceeds that for sequences learned from tabula rasa.

Algorithms↗

Surgical management of tubal infertility. A regional study.

OBJECTIVE: To investigate an unselected group of patients in a regional area undergoing tubal surgery for infertility and to identify those women who would benefit from surgery and those who should be referred directly to in vitro fertilization (IVF). DESIGN: A retrospective study based on medical records and questionnaires. SETTING: The Departments of Obstetrics and Gynecology, Gentofte. Glostrup and Herlev Hospitals, University of Copenhagen, Denmark. SUBJECTS: Two hundred and thirty-six women with primary or secondary infertility undergoing tubal surgery or adhesiolysis during a five year period from 1985 to 1989 with a follow-up period of minimum of 24 months. RESULTS: Ninety-four women (40%) became pregnant at least once and accounted for the total number of 144 pregnancies. One hundred and forty-two patients (60%) did not become pregnant. The delivery rate was 25%, and 37 women (16%) had at least one ectopic pregnancy. There were no significant differences in the delivery rates of the operations in between, but the risk of ectopic pregnancy was significantly lower after adhesiolysis only than after tubal surgery (p < 0.05). The initial laparoscopic findings could not be used to predict the probability of intrauterine pregnancy. CONCLUSION: There is still a place for surgical treatment of tubal infertility, but the risk of ectopic pregnancy should be taken into account before a decision concening line of treatment is made.

Adult↗

Ultrasonic texture and volume of testicles in infertile men.

Ultrasound scanning of the testes and surgical biopsy were performed in 95 infertile men to evaluate the use of ultrasound in male infertility. Ultrasonic testicular volume was calculated using three measurements and the formula of an ellipsoid, and the ultrasonic texture was evaluated and given a score from 1 to 5, indicating increasing degrees of irregularity. The median score was 3 (range 1-5), which was higher than previously found in normal men (median score 2; range 1-5; P < 0.0001). The ultrasonic texture score was lower in testes with a uniform pattern of 100% spermatogenic tubules compared with the rest, both for the right (P < 0.001) and for the left (P < 0.0005) testis. Texture score was correlated with the number of obliterated tubules for both testes (P < 0.001). The mean ultrasonic testicular volume of the right testis was 10.30 ml, and that of the left 10.26 ml. Both were smaller compared with the findings in normal men (P < 0.0001). Ultrasonic testicular volume was negatively correlated with texture score (P < 0.001). A positive correlation between ultrasonic volume and sperm count was seen (P < 0.001). Sperm count was negatively correlated with texture score if calculated together with data from 119 men from the general population (P < 0.001). The study shows that ultrasonic volume and texture are valuable parameters in the evaluation of infertile men.

Adult↗

Salpingitis isthmica nodosa in female infertility and tubal diseases.

Salpingitis isthmica nodosa (SIN) is a condition of nodular thickening of the proximal Fallopian tube. The purpose of this study was to investigate the occurrence, distribution and frequency of SIN in Danish women salpingectomized because of tubal pregnancy or salpingitis and to correlate SIN with infertility, pregnancies, outcome of pregnancies, births, pelvic inflammatory disease and salpingitis. Sections from the isthmus were present in the specimens from 223 tubes from 193 patients and were analysed by the same pathologist. Originally, SIN was found in 12 patients but on re-examination, it was found in 24 patients. Ten women with SIN were bilaterally salpingectomized. Only one woman had SIN in both tubes. Women with SIN gave birth to as many children as women without SIN. After SIN had been diagnosed, no children were born, but this was not statistically different from the frequency of births in the non-SIN group after salpingectomy. Women with SIN had histological signs of salpingitis more often than women without SIN, but SIN complicated with salpingitis did not influence the number of children or tubal pregnancies. Women with SIN had a greater risk of two or more tubal pregnancies than women without SIN.

Adult↗

Male or female sterilization: a comparative study.

The study compares 709 males and 546 females recruited from a well-defined geographic area and sterilized during a 5-year period at the same hospital. Medical records were reviewed and questionnaires sent out. Widespread satisfaction with the sterilization was found. The sterilized women had experienced contraceptive side effects and failures more often than the men. Only 70% of the laparoscopic sterilizations could be carried out during a 1-day admission, 25% of the women complained about long-term sequelae, and there were 1% failures. The vasectomies were carried out on an outpatient basis, there were few postoperative symptoms, and 0.5% failures were recorded. Female sterilization was at least four times as expensive as vasectomy. It is concluded that vasectomy is generally to be preferred to female sterilization, and that the preoperative guidance should involve both man and wife.

Adult↗