"Extracts from "Clinical evidence": Menopausal symptoms

DefinitionMenopause begins one year after the last menstrual period. Symptoms often begin in the perimenopausal years.Incidence/prevalenceIn the United Kingdom the mean age for the menopause is 50 years 9 months. The median onset of the perimenopause is between 45.5 and 47.5 years. One Scottish survey (of 6096 women aged 45 to 54 years) found that 84% had experienced at least one of the classic menopausal symptoms, with 45% finding one or more symptoms a problem.¹

Interventions

• Beneficial:OestrogensTibolone

• Likely to be beneficial:ProgestogensClonidine

• Unknown effectiveness:Phyto-oestrogensTestosteroneAntidepressants

PrognosisMenopause is a physiological event. Its timing may be genetically determined. Although endocrine changes are permanent, menopausal symptoms such as hot flushes, which are experienced by about 70% of women, usually resolve with time.² However, some symptoms, such as genital atrophy, may remain the same or worsen.AimsTo reduce or prevent menopausal symptoms, and to improve quality of life with minimum adverse effects.OutcomesFrequency and severity of vasomotor, urogenital, and psychological symptoms; quality of life.MethodsClinical Evidence search and appraisal December 1999. We included only randomised controlled trials (RCTs) and systematic reviews that met Clinical Evidence quality criteria.BenefitsVasomotor symptoms: We found no systematic review. We found over 40 RCTs comparing oestrogen versus placebo and various preparations and/or routes against each other. Most found that oestrogen reduced vasomotor symptoms (data from one RCT in 875 women: odds ratio 0.53, 95% confidence interval 0.31 to 0.93).³ Two RCTs found that transdermal oestrogen at a low dose of 25 μg daily reduced severity of vasomotor symptoms compared with placebo.^4,5 Urogenital system: We found one systematic review (search date 1995) and three subsequent RCTs. The review pooled data from six RCTs.⁶ It found that oestrogen improved urogenital symptoms regardless of the route of administration (no figures available). One subsequent RCT (n=136) found that low dose transdermal oestrogen (25 μg daily) combined with norethisterone acetate significantly reduced vaginal dryness and dyspareunia compared with placebo over six months.⁴ Two other RCTs (n=192) found that local administration of oestrogen using a silicone oestradiol releasing vaginal ring over 24-36 weeks improved vaginal oestrogenisation and pH compared with placebo.^7,8 One of these trials also found a significant reduction in incidence of urinary tract infection in treated women (P=0.008).⁷ Psychological symptoms: We found one systematic review (search date 1995, 14 RCTs, 12 cohort studies), which found that oestrogen reduced depressed mood among menopausal women.⁹ Duration of treatment ranged from one month to two years. Data pooling for oestrogen versus placebo (10 studies) found that oestrogen reduced depressive symptoms (no figures available). We found no RCTs of oestrogen treatment in women with clinically proved depression. We found one systematic review (search date 1996, 10 controlled trials, 9 observational studies) of the effects of oestrogen on cognitive function in postmenopausal women and women with Alzheimer''s disease.¹⁰ Studies were too weak to allow reliable conclusions. An additional crossover RCT (n=62) found a beneficial effect of oestrogen on sleep quality compared with placebo over seven months.¹¹ Quality of life: We found no systematic review. We found four RCTs (639 women, 3 RCTs placebo controlled, 3 versus progestogen), which found significant improvement in quality of life in women treated with oestrogen compared with baseline or placebo.^12–15 The largest RCT (242 women) found that oestrogen improved quality of life (P=0.0003) and wellbeing (P=0.003) compared with placebo over 12 weeks.¹²HarmsMany RCTs have found that oestrogen causes weight gain and breast tenderness in the short term. Although many women report an increase in weight when starting oestrogen, we found no evidence from RCTs that oestrogen causes significant weight gain in the long term. The most important long term adverse effects are increased risk of venous thromboembolic disease, endometrial cancer, and breast cancer.^16–18 The relation between oestrogen (as hormone replacement therapy) and breast cancer was reviewed in a reanalysis of 51 studies of more than 160 000 women.¹⁹ The review found that the risk of breast cancer increased by 2.3% (1.1% to 3.6%) each year in women using hormone replacement therapy. Five or more years after hormone replacement therapy was stopped, there was no significant excess of breast cancer.¹⁹CommentMany studies used selected populations such as women attending hospital clinics, who may be different in their behaviour, personality, and symptom profile to women of the same age seen in primary care or those who do not seek medical advice. Option: ProgestogensSummary We found good evidence from RCTs that progestogens reduce vasomotor symptoms. We found no good quality evidence on other outcomes, including quality of life.BenefitsWe found no systematic review. Vasomotor symptoms: We found five RCTs (257 women, all trials less than a year long), which found that women taking progestogens experienced a significant reduction in vasomotor symptoms compared with placebo.^20–24 The single RCT comparing oestrogen alone with progestogen (150 mg of depot medroxyprogesterone for 25 days a month) found that over three months, 18% of women taking oestrogens and 33% taking progestogen reported no vasomotor symptoms.²¹ One RCT (n=102) found that transdermal progesterone cream 20 mg daily improved vasomotor symptoms compared with placebo (P<0.001) but had no beneficial effect on bone density.²⁵ Urogenital system: We found no RCTs evaluating the effects of progestogens alone on urinary incontinence, the lower genital tract, or sex life. Psychological symptoms: We found no RCTs. Quality of life: One RCT of cyclical progestogen plus oestrogen for six months found no evidence of an effect on quality of life.²⁶ We found no studies of progestogen alone on quality of life.HarmsWe found two RCTs that evaluated harms of progestogens. The first compared continuous progestogen (norgestrel) and placebo in 321 women who had undergone hysterectomy and were already taking conjugated oestrogen. It found no difference in symptoms (including weight gain and bloating).²⁷ The second RCT (875 women) compared various oestrogen-progestogen combinations over three years.³ It found that additional progestogen increased breast discomfort (odds ratio 1.92, 1.16 to 3.09). Neither trial found evidence of an effect on cardiovascular events.CommentProgestogen is seldom given alone, which makes it hard to isolate its effects. When it was given without oestrogen, doses of progestogens were high, the lowest dose being 20 mg medroxyprogesterone acetate per day. Option: TiboloneSummary RCTs found that tibolone significantly improved vasomotor symptoms, libido, and vaginal lubrication.BenefitsWe found no systematic review. Vasomotor symptoms: We found three RCTs, two of tibolone versus continuous combined oestrogen/progestogen treatment over 48 and 52 weeks (672 women with menopausal symptoms)^28,29 and one versus placebo over 16 weeks (82 women with menopausal symptoms).³⁰ The first RCT found a slightly greater reduction in hot flushes with the combined regimen than with tibolone over 48 weeks (P=0.01). The second trial found a significant reduction in vasomotor symptoms from baseline in both groups (67/72 women on HRT and 58/68 women on tibolone, P<0.001) but no significant difference between groups. The third trial found tibolone reduced vasomotor symptoms by 39% compared with placebo (P=0.001). Urogenital system: We found two RCTs. The first RCT found no significant difference between tibolone and combined hormonal treatment in terms of subjective reports of vaginal lubrication; both interventions improved lubrication compared with baseline.²⁸ The second RCT (437 women) found that tibolone improved sexual satisfaction compared with oestradiol plus norethisterone (P<0.05).³¹ We found no RCTs examining effects on urinary incontinence. Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs. Bone density: We found nine RCTs, which found that tibolone increased bone density over periods from 6 to 36 months compared with baseline or placebo.³²HarmsWe found no evidence on adverse effects from RCTs. One non-randomised controlled trial found that the main unwanted effect of tibolone was breakthrough bleeding, which occurred in about 10% of users.³³ We found no good evidence of androgenic adverse effects such as hair growth and greasiness of the skin. Two RCTs of short term use found a 33% reduction in plasma high density lipoproteins with tibolone,^34,35 although the long term effects on cardiovascular disease are unknown.CommentNone. Option: Phyto-oestrogensSummary Limited evidence from small RCTs suggests that soy flour, which contains phyto-oestrogens, may relieve vasomotor menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found three placebo controlled RCTs. Two evaluated soy supplements, which contain phyto-oestrogen, using double blind designs; the other, which was not blinded, evaluated isoflavone. The first RCT (58 postmenopausal women) compared soy flour versus wheat flour for 12 weeks and found that hot flushes were reduced significantly more in the group of women using soy flour (40% v 25% reduction).³⁶ The second RCT used a crossover design to evaluate six weeks'' administration of 34 mg soy protein daily. It found reduced severity but not frequency of vasomotor symptoms.³⁷ The third RCT (n=51) used a crossover design to compare isoflavone 40 mg daily with placebo. It found benefit from placebo compared with baseline, but not with isoflavone.³⁸ Urogenital system: We found no RCTs. Psychological symptoms: We found no RCTs. Beneficial effects of treatment on quality of life: We found no RCTs.HarmsWe found no evidence of significant adverse effects.CommentNone. Option: ClonidineSummary Two RCTs found that clonidine reduced vasomotor symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found two RCTs.^39,40 One crossover RCT (66 women) found that clonidine reduced the mean number of flushing attacks in the 14 days after crossover compared with placebo (56.8 v 64.3, P<0.05).³⁰ The second RCT (30 women) found that more women taking clonidine reported reduced flushes at 8 weeks (12/15 v 5/14, P<0.04).⁴⁰ Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs.HarmsThe two RCTs found no significant difference in the incidence of unwanted effects between placebo and active treatment groups.^39,40CommentNone. Option: TestosteroneSummary We found evidence from RCTs that testosterone improves sexual enjoyment and libido. We found no studies evaluating effects on other commonly experienced menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found no RCTs evaluating testosterone alone in women with menopausal symptoms. We found one RCT (93 postmenopausal women) comparing oestrogen alone and oestrogen plus methyltestosterone. This concluded that addition of a small dose of methyltestosterone reduced the dose of oestrogen needed to control menopausal symptoms.⁴¹ Urogenital system: We found two RCTs, one in 40 women and one crossover study in 53 women. Both found benefit from exogenous testosterone on self reported sexual enjoyment, desire, and arousal.^42,43 Psychological symptoms: We found no RCTs. Beneficial effects of therapy on quality of life: We found no RCTs.HarmsWe found no evidence from RCTs or other controlled studies on the incidence of androgenic adverse effects with testosterone.CommentNone. Option: AntidepressantsSummary We found insufficient evidence on the effects of antidepressants on menopausal symptoms.BenefitsWe found no systematic review or RCTs that specifically addressed the effects of antidepressants on menopausal symptoms or quality of life in menopausal women.HarmsWe found no evidence on adverse effects in postmenopausal women. Antidepressants as a group can cause many central nervous system adverse effects, including sedation and agitation, as well as urinary and vision problems, liver dysfunction, and cardiac dysrhythmias.⁴⁴CommentNone.     

Chinchilla "big" and "little" gastrins

Gastrin heptadecapeptides (gastrins I and II which differ in the presence of sulfate on the tyrosine of the latter) have been purified and sequenced from several mammalian species including pig, dog, cat, sheep, cow, human and rat. A 34 amino acid precursor ("big" gastrin), generally accounting for only 5% of total gastrin immunoreactivity, has been purified and sequenced only from the pig, human, dog and goat. Recently we have demonstrated that guinea pig (GP) "little" gastrin is a hexadecapeptide due to a deletion of a glutamic acid in the region 6-9 from its NH2-terminus and that GP "big" gastrin is a 33 amino acid peptide. The chinchilla, like the GP, is a New World hystricomorph. This report describes the extraction and purification of "little" and "big" gastrins from 31 chinchilla antra. Chinchilla "little" gastrin is a hexadecapeptide with a sequence identical to that of the GP and its "big" gastrin is a 33 amino acid peptide with the following sequence: (See text)     

Opossum (Didelphis virginiana) "little" and "big" gastrins

1. "Little" gastrins from most mammalian species are 17 amino acid peptides and the precursor "big" gastrins are 34 amino acid peptides. 2. "Little" gastrins of the New World hystricomorphs, guinea-pig and chinchilla, are 16 amino acid peptides due to deletion of a glutamic acid in the region 6-9 from their NH2-terminus and the corresponding "big" gastrins are 33 amino acid peptides. 3. Antral gastrins from the opossum, a New World marsupial, have a glutamic acid deletion in the same region as the hystricomorph gastrins. 4. Opossum "big" gastrin is a 33 amino acid peptide with the following sequence: less than ELGPQDLPYLTADLSKKQGPWLEEEEAYGWMDF#.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Proteolytic Digestion Patterns of "Soluble"and "Detergent-Soluble"Bovine Caudate Nucleus Acetylcholinesterases

Abstract: The structures of purified "soluble"and "detergent-soluble"bovine caudate nucleus acetylcholinesterases were compared by peptide mapping on polyacrylamide gels. The digestion products generated from the two acetylcholinesterases on proteolysis by a given protease ( Staphylococcus aureus V8 protease, α-chymotrypsin, or papain) are remarkably similar as judged from the electrophoretic band patterns. We conclude that the "soluble"and "detergent-soluble"acetylcholinesterases from bovine caudate nucleus share a common evolutionary origin.     

The use of multifolded pericranial flaps as "plugs" and "pads"

Pericranial flaps are thin and, hence, their volumes are small. Therefore, their use for soft-tissue augmentation has not been popular. In this article, the author introduces a new concept: the use of a multifolded pericranial flap as a "plug" or a "pad" for localized contour defects. Eight patients were included in the study. In all cases, an anteriorly based pericranial flap was used, and the flap was folded on itself several times to increase its bulk. The results were satisfactory in all patients. The literature on the topic is reviewed, and the blood supply of pericranial flaps is discussed.     

THE POWER OF THE " A" -" NOT A" METHOD

The " A" - " Not A" method is a rating method with two categories. It is often treated as a discrimination method. Unlike forced choice procedures, the Thurstonian model for this method involves a choice criterion. In statistical tests, it is treated as a comparison of two proportions. In this paper, the power for hypothesis tests involving the monadic and replicated monadic " A" - " Not A" method is discussed. The power functions and the sample sizes needed for 80% power are given based on Thurstone's δ. Designs with equal and unequal allocations for A and A (Not A) samples are considered. The power of the method is also compared with that of four forced choice methods under the assumption that the perceptual variance is identical among methods. The comparison shows that, in general, the power for the five methods ranks from high to low: the 3-AFC, 2-AFC, " A" - " Not A", triangular and duo-trio. The comparison also shows that, based on the same number of panelists and/or the same sample size for the A and A⁻ samples for the methods, if the panelists are not too discrepant and the choice criterion in the " A" - " Not A" method is not too strict or too lax, the power of the " A" - " Not A" method is very close to that of the 2-AFC method.     

Italy's "Southern Question": Orientalism in One Country

Italy's "Southern Question": Orientalism in One Country. Jane Schneider. ed. New York: Berg, 1998. 299 pp.     

用铀子系法测定河套人和萨拉乌苏文化的年代

用铀子系法中的~(230)Th增长法测定了河套人与萨拉乌苏文化的年代。并用~(231)Pa增长法对所测年代的可靠性作了检验。 根据测得数据,萨拉乌苏组的沉积时代不早于晚更新世中期,其上部不超过三万年,下部为距今3—5万年左右。 考虑到人化石及旧石器的出土层位,河套人与萨拉乌苏文化的年代应为距今3.7—5万年左右。     

"Timers" and "scanners" among orientation detectors in cat visual cortex

Experiments were carried out on immobilized cats to determine whether, among visual cortical neurons, besides the "scanners" described by the writers previously, which are responsible for a dynamic shift of preferred orientation, there exist also "timer" cells, which do not change the temporal parameters of their responses during rotation of a flashing stimulus. The existence of such cells is postulated on the basis of the previous hypothesis on the spatiotemporal principle of orientational coding. Of 76 neurons tested 27, i.e., 36%, were classed as "timers." They differed significantly from the "scanners" (64%) by the following properties: shorter latent periods, shorter time to the peak and duration of responses, more rapid rise of discharge frequently in the volley. The "timers" had less sharp orientational tuning and a low ratio between values of responses to presentation of preferred and worst stimuli (on account of a considerable increase in responses to unpreferred orientations). The set of preferred orientations of the "timers" was found to be highly selective and additional relative to the corresponding distribution for "scanners."The difference in frequency-temporal properties of responses and orientational tuning of the "timers" and "scanners" and their possible mutually complementary role in orientational coding at the visual cortical level are discussed.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 35–43, January–February, 1985.     

About true science and false words: "oxidase", "cryostat" and "apoptosis".

The author examines the concept's deviations due to some erroneous constructions of words, by considering the words oxidase, cryostat and apoptosis. But he insists much more on the bandy-legged structures linked to these words which deviate totally from any significance attached "officially" to them and leading to false deductions. The author conveys all scientists to use: oxydase, cryotome and Programmed Cell Death, or PCD, forgetting all other queer non-sense words. He suggests to use the word "cytoptosis".     

Genealogy of wine grape cultivars: "Pinot" is related to "Syrah"

Since the domestication of wild grapes ca 6000 years ago, numerous cultivars have been generated by spontaneous or deliberate crosses, and up to 10 000 are still in existence today. Just as in human paternity analysis, DNA typing can reveal unexpected parentage of grape cultivars. In this study, we have analysed 89 grape cultivars with 60 microsatellite markers in order to accurately calculate the identity-by-descent (IBD) and relatedness (r) coefficients among six putatively related cultivars from France ("Pinot", "Syrah" and "Dureza") and northern Italy ("Teroldego", "Lagrein" and "Marzemino"). Using a recently developed likelihood-based approach to analyse kinship in grapes, we provide the first evidence of a genetic link between grapes across the Alps: "Dureza" and "Teroldego" turn out to be full-siblings (FS). For the first time in grapevine genetics we were able to detect FS without knowing one of the parents and identify unexpected second-degree relatives. We reconstructed the most likely pedigree that revealed a third-degree relationship between the worldwide-cultivated "Pinot" from Burgundy and "Syrah" from the Rhone Valley. Our finding was totally unsuspected by classical ampelography and it challenges the commonly assumed independent origins of these grape cultivars. Our results and this new approach in grape genetics will (a) help grape breeders to avoid choosing closely related varieties for new crosses, (b) provide pedigrees of cultivars in order to detect inheritance of disease-resistance genes and (c) open the way for future discoveries of first- and second-degree relationships between grape cultivars in order to better understand viticultural migrations.     

The "Moi-peau"

To construct a coherent identity, humans must distinguish what belongs to the external, perceived world from what belongs to their own inner world and the inner world of other individuals. Based on the theory developed by S. Freud and on work by ethologists, a number of psychoanalysts (J. Bowlby, R.A. Spitz, D.W. Winnicott, etc.) have underlined the importance of early tactile exchanges with the mother if a child is to become an autonomous individual who feels secure within what he or she perceives to be sound and reliable mental and physical boundaries. More recently, other psychoanalysts (E. Bick, W.R. Bion, etc.) have studied the fantasized mental structures that form the limits between an individual's inner mental space and the external world (including other individuals). As part of this theoretical psychoanalytical movement, Didier Anzieu, a French psychoanalyst, started to develop the concept of the "Moi-peau" in 1974. The "Moi-peau" designates a fantasized reality that a child uses during its early development to represent itself as "me", based on its experience of the body surface. The child, enveloped in its mother's care, fantasizes of a skin shared with its mother: on one side the mother (the outer layer of the "Moi-peau"), and on the other side the child (the inner layer of the "Moi-peau"). These two layers must separate gradually if the child is to acquire its own me-skin. D. Anzieu's work allowed dermatologists and other specialists, such as pediatricians, to focus on the quality of early tactile exchanges between a mother and her child, including the child with a chronic skin disorder. It also helped dermatologists to recognize patients with "borderline" states, which are particularly frequent in dermatology (ereutophobia, dysmorphophobia, tattooing, self-mutilation, artefacta dermatitis). These borderline patients are adults who, as a result of their mental conflicts, adopt defense mechanisms derived from both neurotic and psychotic functioning. Their complaints reflect difficulties with the solidity of their mental and physical limits: their real skin is metaphorically linked to the fantasized mental structure that delimits the individual mental space. Among other clinical characteristics, they have a "pathology of action" and frequently attack their own skin, paradoxically, in order to test the solidity and reliability of their own limits. Finally, D. Anzieu's work encouraged dermatologists to use psychotherapeutic approaches in parallel to classical dermatologic approaches, when necessary, and helped them better understand how psychoanalysts work with patients who have not yet acquired their own "Moi-peau". As a result, D. Anzieu was among the first to reconcile dermatologists and psychoanalysts.     

14 cases of "anti-N" antibodies in hemodialysis patients in Marseille

Some medical centers re-use dialysis units sterilized with formaldehyde. In a study of 239 cases, 14 "anti-N" antibodies were found only among the 59 patients of the medical centers which re-use dialysis units. The action of formol seems to be confirmed by the presence of "anti-N" in 2 patients who had undergone prosthesis several times, but not dialysis. For these prostheses, a bone cement, sterilized with formol, was used. These "anti-N" are very often associated with cold autoagglutinins, and appear regardless of the patient's MN group. The action of formaldehyde suggests the following hypotheses:--antigenic modification;--disturbances in the immune response mechanisms;--a combination of the two. In the first hypothesis: the action of formol discovered since a long time on red cells. In the second hypothesis: the existence of auto-agglutinins only among the 14 hemo-dialysis patients with anti-N antibodies.     

From "butyribacterium" to "E. coli": an essay on unity in biochemistry

New ideas in science frequently arise from neglected or distorted antecedents. This essay deals with the idea of biochemical unity, encapsulated in Jacques Monod's well-known phrase, dating from 1954: "Anything found to be true of E. coli must also be true of elephants." An earlier version of this phrase,--"From the elephant to butyric acid bacterium--it is all the same!"--was coined in 1926 by the Dutch microbiologist Albert Jan Kluyver. In that year Kluyver and his associate Hendrick Jean Louis Donker published a celebrated paper, "Unity in Biochemistry." The concept of biochemical unity had many antecedents, but these had never caught on. The Kluyver-Donker paper has often been regarded to provide a boost to biochemical and especially to microbiological thinking. Its interpretations and misinterpretations represent an encapsulated history of biochemistry. The present paper examines the history of the concept of biochemical unity from before to beyond Kluyver, investigates the two "elephant" phrases and their possible relationships, and ends with a discussion of the attractiveness of unifying ideas in science.     

Meaning, Medicine, and the "Placebo Effect"

Meaning, Medicine, and the "Placebo Effect" Daniel Moerman Cambridge: Cambridge University Press, 2002. xiii. 172 pp.     

Genetic evidence of "American" and "European" type symbiotic algae of Paramecium bursaria Ehrenberg

Paramecium bursaria is composed of a "host" ciliate and a "symbiont" green alga. Based upon physiology, DNA hybridization and virus infection, two types of symbionts, called "American" type and "European" type, have been reported to date. Here, we determined the 18S rDNA and internal transcribed spacer 2 (ITS2) regions for both "American" and "European" types. Sequence features clearly separated into two lineages; NC64A (USA), Syngen 2-3 (USA), Cs2 (Chinese), MRBG1 (Australian), and Japanese strains belong to the "American", whereas PB-SW1 (German) and CCAP 1660/11 (British) strains belong to the "European". In "American" 18S rDNA, three introns were inserted in the same positions as for previously described Japanese symbionts. In "European" 18S rDNA, a single intron occurred in a different position than in the "American". Between the types, sequence differences were seven or eight nucleotides (0.39 %) in the 18S rDNA exon, and more than 48 nucleotides (19.2 %) in ITS2 regions. We subsequently sequenced the host 18S rDNA. As a result, two groups: Cs2, MRBG1, and Japanese strains, and PB-SW1 and CCAP 1660/11 strains, were separated (with 23 substitutions and 4 insertions or deletions between the groups). The congruent separations between hosts and symbionts may imply that the type of symbiont depends on the host type.     

Deceiving appearances: signaling by "dead" and "fractured" receptor protein-tyrosine kinases

The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. This tidy picture has, however, some strange characters lurking around the edges. Cases have now been identified in which RTKs lack kinase activity, but, despite being "dead" appear to have roles in signal transduction. Even stranger are the cases in which genes encoding RTKs produce protein products consisting of only a portion of the kinase domain. At least one such "fractured" RTK appears to be involved in signal transduction. Here we describe how these strange molecules might function and discuss the questions associated with their evolution. BioEssays 23:69-76, 2001.     

A novel Fryns "Anophthalmia-plus" syndrome associated with primary hypothyroidism

A novel Fryns "anophthalmla-plus" syndrome associated with primary hypothyroidism: Here, we report a newborn male with "anophthalmia-plus" syndrome and primary congenital hypothyroidism. To our knowledge this is the first case of 'anophthalmia-plus' syndrome associated with congenital hypothyroidism in the literature up to date.