Successful pregnancy in a woman with ovarian failure associated with mutation in the beta-subunit of luteinizing hormone.

BACKGROUND: We report a successful pregnancy in a woman with severe ovarian dysfunction and infertility associated with a variant beta-subunit of luteinizing hormone (LH). METHOD/OUTCOME: A 35-year-old woman consulted our unit for infertility. Laparoscopy and ultrasonography showed obstruction of the right tube and ovulation from the right ovary only. Human menopausal gonadotrophin (hMG) therapy was used for six subsequent cycles, but did not result in conception. Subsequently, marked elevation of follicle-stimulating hormone (FSH) and testosterone, together with polycystic ovary (PCO) were noted. The patient failed to respond to ovarian stimulation by hMG. Severe ovarian dysfunction such as premature ovarian failure (POF) was strongly suspected. Sequence analysis of the LH beta-subunit gene indicated heterozygosity for point mutations Trp(8) to Arg(8) and Ile(15) to Thr(15) in the coding sequence. LH hypersecretion resembling that seen in PCO syndrome was observed. Induction of ovulation by hMG was successful in the first cycle in which the basal LH and FSH were well controlled with gonadotrophin-releasing hormone analog following estrogen-progesterone replacement. She conceived and delivered a healthy male infant at term. CONCLUSION: Clinicians should be clinically aware of patients with immunologically anomalous LH variant who might be at risk of developing ovarian failure within a relatively short time span. Pertinent treatment should be applied without delay in such cases.     

Ca2+ is Required by Clubroot Resistant Turnip Cells for Transient Increases in PAL Activity that Follow Inoculation with Plasmodiophora brassicae

Phenylalanine ammonia‐lyase (PAL, EC 4.3.1.5) activity in clubroot disease‐resistant turnip calli was transiently increased by 20 h after the inoculation with Plasmodiophora brassicae spores. The magnitude of the increase in PAL activity was four to six times higher than constitutive PAL activity. There was no transient increase in PAL activity in susceptible calli. Preincubation of calli in Ca²⁺‐free medium or the removal of Ca²⁺ from cell surfaces by ethylene glycol bis(2‐aminoethyl ether)‐N,N,N′,N′‐tetraacetic acid‐chelation, completely inhibited induced PAL activity. The influx of exogenous Ca²⁺ into cells appears necessary for this pathogen induced PAL activity. Verapamil and the calmodulin inhibitor W7 almost completely inhibited induced PAL activity at 1 and 0.1 mm , respectively. Neomycin, ruthenium red and (1‐(6‐[(17β‐3‐Methoxyestra‐1,3,5‐(10)‐trien‐17‐yl)amino]hexyl)‐1H‐pyrrole‐2,5‐dione) did not inhibit induced PAL activity. Thus, verapamil and N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalenesulphonamide hydrochloride‐sensitive Ca²⁺‐mediated signalling process appear necessary for P. brassicae induced PAL activity. As the protein synthesis inhibitor cycloheximide (CHX) blocked the induced increasing PAL activity, de novo synthesis of PAL appears to be required for turnip cell defence reactions against P. brassicae.     

Cloning and characterization of mouse klk27, a novel tissue kallikrein expressed in testicular Leydig cells and exhibiting chymotrypsin-like specificity.

A cDNA clone of a new mouse tissue kallikrein, designated mKlk27, was isolated from an adult mouse testis cDNA library. mKlk27 was expressed in the submaxillary glands and testis of the mouse. In testis, mKlk27 gene was expressed exclusively in the Leydig cells of the adult mouse. Active recombinant mKlk27 exhibited chymotrypsin-like cleavage specificity. A single amino-acid substitution of Gly for Asp at position 209 in mKlk27 resulted in complete loss of its chymotryptic activity but acquisition of tryptic activity. mKlk27 effectively hydrolyzed casein, gelatin and fibronectin. Insulin-like growth factor binding protein-3 was also hydrolyzed by recombinant mKlk27. These results suggest that mKlk27 plays an important role in association with the function of the adult mouse testis.     

Physiological evaluation of temperature effect on the growth processes of the mysid, Neomysis intermedia Czerniawsky

Ingestion, respiration, and molting loss rates were measuredover the 3 – 29°C range in Neomysis intermedia. Weightspecific rates of these physiological processes ranged from2 to 140% body C day^–1 for ingestion, from 2 to 15% bodyC day^–1 for respiration, and from 0.1 to 5% body C day^–1for molting loss. All weight-specific rates showed a logarithmicdecrease with a logarithmic increase in body weight, and a logarithmicincrease with a linear increase in temperature below 20 or 25°C.The effect of temperature, however, was different between thephysiological rates, with a large temperature dependency foringestion (Q₁₀ = 2.6 –3.9) and molting loss (Q¹⁰ = 2.9– 3.6) and a moderate temperature dependency for respiration(Q₁₀ = 1.9 – 2.1). Calculated assimilation efficiencychanged with body size, but was constant over the temperaturerange examined. Allocation of assimilated materials varied witha change in temperature, reflecting the different temperaturedependence between physiological processes. It was deduced thatthe strong temperature dependency of the growth rate in N. intermediaobserved in the previous studies resulted from the large temperatureeffect on ingestion and assimilation rates, superimposed bythe different allocation of assimilated materials. ¹Present address: Department of Botany, University of Tokyo,Hongo, Tokyo 113, Japan     

A model for the spatio-temporal organization of DNA replication in mammalian cells

The spatio-temporal organization of chromosomal DNA replication was analyzed using a model based on a "DNA unit" (or decondensation unit) hypothesis. The model is an extension of the fork movement theory of Huberman & Riggs (1968) and can account for a partially deterministic and partially stochastic order of DNA replication in chromosomes. It presumes that each chromosome is composed of DNA units that are arranged in sequence and that are replicated in parallel. A deterministic wave of chromatin decondensation propagates along the DNA unit continuously and progressively providing a field for the random activation of replication origin. Assignment of replication times to DNA compartments by a Monte Carlo method was programmed based on the model and the program was used to stimulate DNA synthesis rate curves that can be measured by the method of Dolbeare et al. (1983, 1985). The shape of the curve is shown to constrain possible parameter values of the model, which include the rate of fork movement, the fraction of chromatin that is decondensed at the start of S-phase, the initial number of origins activated, the rate at which new origins are activated, etc. The chromosomal organization that controls the molecular level of DNA replication is briefly reviewed and its relevance to the model is also discussed.     

Sister-chromatid exchanges induced by ultraviolet light in Bloom's syndrome fibroblasts

The relationships between the cytotoxic effect of ultraviolet light and the UV-induced sister-chromatid exchanges (SCEs) were compared among fibroblast cell strains from two unrelated Bloom's syndrome (BS) patients, one xeroderma pigmentosum (XP) patient belonging to complementation group A and two unrelated normal controls. The "net" induced SCEs as a function of UV fluence, obtained by subtracting spontaneous SCEs from observed SCEs, were much higher in both BS cells and XP group A cells than in normal cells. The relative efficiency of induced SCE, defined as the "net" induced SCEs as a function of surviving fraction after UV irradiation, was higher in BS cells than in normal and XP cells, and there was essentially no difference between XP and normal cells. These results imply that in addition to the extremely high frequency of spontaneous SCEs, the increased efficiency in UV induction of SCEs may reflect the intrinsic defect(s) in BS cells.     

Stressful life events preceding the acute onset of schizophrenia: A cross-national study from the World Health Organization

This study reports on the findings from a WHO sponsored cross-national investigation of life events and schizophrenia. Data are presented from a series of 386 acutely ill schizophrenic patients selected from nine field research centers located in developing and developed countries (Aarhus, Denmark; Agra, India; Cali, Colombia; Chandigarh, India; Honolulu, USA; Ibadan, Nigeria; Nagasaki, Japan; Prague, Czechoslovakia; Rochester, USA). On a methodological level, the study demonstrates that life event methodologies originating in the developed countries can be adapted for international studies and may be used to collect reasonably reliable and comparable cross-cultural data on psychosocial factors affecting the course of schizophrenic disorders. Substantive findings replicate the results of prior studies which conclude that socioenvironmental stressors may precipitate schizophrenic attacks and such events tend to cluster in the two to three week period immediately preceding illness onset.The paper was prepared by these authors on behalf of the collaborating investigators listed on page 196.     

Sequence of an intestinal cDNA encoding human motilin precursor

A cDNA clone encoding the human motilin precursor was isolated from an intestinal library using synthetic oligonucleotide probes. The predicted amino acid sequence indicates that the motilin precursor consists of 115 amino acids and includes a 25-residue N-terminal signal peptide followed by the 22-amino-acid motilin sequence and a long, 68-residue C-terminal peptide. The amino acid sequence of human motilin predicted from the cDNA sequence is identical to its porcine counterpart, which has been determined by protein sequencing. Proteolytic processing of promotilin to motilin occurs at the sequence, Lys-Lys, this being the first reported instance of processing occurring at a pair of Lys residues. In other precursors it occurs at Lys-Arg, Arg-Arg, Arg, or very rarely Lys.