Lymphatic vessels arise from specialized angioblasts within a venous niche.

How cells acquire their fate is a fundamental question in developmental and regenerative biology. Multipotent progenitors undergo cell-fate restriction in response to cues from the microenvironment, the nature of which is poorly understood. In the case of the lymphatic system, venous cells from the cardinal vein are thought to generate lymphatic vessels through trans-differentiation. Here we show that in zebrafish, lymphatic progenitors arise from a previously uncharacterized niche of specialized angioblasts within the cardinal vein, which also generates arterial and venous fates. We further identify Wnt5b as a novel lymphatic inductive signal and show that it also promotes the 'angioblast-to-lymphatic' transition in human embryonic stem cells, suggesting that this process is evolutionarily conserved. Our results uncover a novel mechanism of lymphatic specification, and provide the first characterization of the lymphatic inductive niche. More broadly, our findings highlight the cardinal vein as a heterogeneous structure, analogous to the haematopoietic niche in the aortic floor.

Long-term prognosis of patients with major depression and silent cerebral infarction.

OBJECTIVE: Many studies have examined the effects of cerebrovascular changes on treatment response in geriatric depression. However, few such studies have examined the relationship between cerebrovascular changes and long-term prognosis. We examined the effects of cerebrovascular changes on the course of geriatric depressive symptoms, dementia rates, and mortality over a follow-up period of approximately 10 years. METHOD: Participants were 84 patients with major depression (age of onset over 50 years); patients suffering from strokes, neurological disorders, and other psychiatric disorders were excluded. Magnetic resonance imaging findings were used to classify all patients into silent cerebral infarction (SCI)-positive (n = 37) or SCI-negative groups (n = 47). Prognoses were ascertained using a review of clinical charts and mailed questionnaires. RESULTS: Only 5% of patients with SCI were able to maintain remission whereas 36% of patients without SCI were able to do so. Total duration of depressive episodes was significantly longer in the SCI-positive group than in the SCI-negative group. SCI was also associated with a higher risk of dementia. CONCLUSION: The results of this long-term follow-up study demonstrate that the presence of SCI is associated with a relatively poor prognosis in geriatric depression.

Hurthle cell adenoma of the thyroglossal duct.

Neoplasia in thyroglossal duct cysts or ectopic thyroid tissue deposits is rare but well recognized. The first known case of Hurthle cell adenoma in thyroglossal duct anomaly is described. The pathologic course and treatment of Hurthle cell tumors in general is reviewed. Treatment was based on the view that neoplasms in thyroglossal duct remnants represent changes in the ectopic thyroid tissue.

Changes in auditory P300 in patients with major depression and silent cerebral infarction.

We examined event-related potentials in patients with senile depression and silent cerebral infarction (SCI) to clarify the features of the P300 component. P300 event-related potentials were recorded in drug-free depressed patients (N = 16) and normal controls (N = 17). All patients underwent magnetic resonance imaging and were classified as SCI-positive (N = 7) or SCI-negative (N = 9). In depressed patients, the P300 was reexamined after antidepressant treatment. Prior to treatment, P300 amplitudes in depressed patients were significantly smaller than those in normal controls (P < 0.01). P300 amplitudes increased significantly in SCI-negative patients following recovery (P < 0.05), but did not change in SCI-positive patients. SCI may interrupt the treatment-related P300 amplitude increase in depressed patients.

The 3-year course and outcome of patients with major depression and silent cerebral infarction.

We retrospectively investigated the relationship between major depression and silent cerebral infarction (SCI) over a 3-year period in 64 patients older than 50 years of age with unipolar depression. All patients underwent magnetic resonance imaging (MRI) at their first admission for depression and were classified into groups based on the presence or absence of SCI. The number of admissions due to depression was greater in the SCI (+) group (N = 32) than in the SCI (-) group (N = 32) (P < 0.05). The incidences of delirium and neurological disorders were significantly higher in the SCI (+) group than in the SCI (-) group. Our findings suggest that patients with depression and SCI had a higher rate of hospitalization and were more likely to develop psychiatric and neurological disorders than patients with depression without SCI.

Ovarian endometrioid carcinoma with an adenofibromatous pattern.

We report the case of a 66-year-old postmenopausal woman who underwent unilateral oophorectomy for an ovarian endometrioid carcinoma with an unusual adenofibromatous stromal reaction pattern. She is presently alive, well and without clinical evidence of tumour two years after surgery. Adenofibromatous or cystadenofibromatous reaction is a peculiar reactive ovarian stromal change most probably induced by the invading neoplastic epithelial cells. No definite conclusions have been reached regarding the prognostic significance of this special stromal tissue reaction in cases of endometrioid carcinoma of the ovary.

[Cervical ectopic pregnancy].

Cervical pregnancy is a rare but serious complication. The most frequent presenting symptom is vaginal bleeding, and is thus common in inevitable abortion. Examination reveals a dilated cervix containing products of conception derived from the emptied uterine cavity. The pathologic criteria are cervical glands opposite the placental site, attachment to and actual invasion of the cervix by the placenta, a portion of the placenta below the posterior reflection, and no fetal parts in the corpus uteri. Treatment ranges from hysterectomy to treatment with chemical agents, mostly methotrexate. We present a case of ectopic, cervical pregnancy with exaggerated placental site in the cervix.

Genes linked by fusion events are generally of the same functional category: a systematic analysis of 30 microbial genomes.

Recent work in computational genomics has shown that a functional association between two genes can be derived from the existence of a fusion of the two as one continuous sequence in another genome. For each of 30 completely sequenced microbial genomes, we established all such fusion links among its genes and determined the distribution of links within and among 15 broad functional categories. We found that 72% of all fusion links related genes of the same functional category. A comparison of the distribution of links to simulations on the basis of a random model further confirmed the significance of intracategory fusion links. Where a gene of annotated function is linked to an unclassified gene, the fusion link suggests that the two genes belong to the same functional category. The predictions based on fusion links are shown here for Methanobacterium thermoautotrophicum, and another 661 predictions are available at http://fusion.bu.edu.

Chronic infection with Epstein-Barr virus, Chlamydia and hepatitis A virus, terminating in cirrhosis and nasopharyngeal carcinoma.

We describe a 27-year-old woman who presented with infertility, and over the subsequent 7 years developed chronic Epstein-Barr virus infection, hepatitis A, cirrhosis and nasopharyngeal carcinoma. Serological evidence of chronic infection with Chlamydia, Epstein-Barr virus and hepatitis A virus was documented.

Psychosocial stressors in patients with major depression and silent cerebral infarction.

BACKGROUND AND PURPOSE: We previously found that silent cerebral infarction (SCI) was present in most of the patients older than 50 years with major depression who were examined. The present study was designed to clarify the relationship between psychosocial stressors and SCI in patients with major depression. METHODS: Forty-two patients with unipolar depression underwent MRI and were classified as SCI-negative (n = 19) or SCI-positive (n = 23). The SCI-positive group was subclassified into those with moderate SCI (n = 16) and those with severe SCI (n = 7). The relationship between the patients' DSM-III-R axis IV scores and SCI was evaluated. RESULTS: The axis IV score was significantly lower in the SCI-positive group than in the SCI-negative group (P < .05). Within the SCI-positive group, the mean axis IV score was significantly lower in those with severe SCI than in those with moderate SCI (P < .05). CONCLUSIONS: Our findings suggest that depression in patients with SCI involves more neurological factors than psychosocial stressors.

The complete human olfactory subgenome.

Olfactory receptors likely constitute the largest gene superfamily in the vertebrate genome. Here we present the nearly complete human olfactory subgenome elucidated by mining the genome draft with gene discovery algorithms. Over 900 olfactory receptor genes and pseudogenes (ORs) were identified, two-thirds of which were not annotated previously. The number of extrapolated ORs is in good agreement with previous theoretical predictions. The sequence of at least 63% of the ORs is disrupted by what appears to be a random process of pseudogene formation. ORs constitute 17 gene families, 4 of which contain more than 100 members each. "Fish-like" Class I ORs, previously considered a relic in higher tetrapods, constitute as much as 10% of the human repertoire, all in one large cluster on chromosome 11. Their lower pseudogene fraction suggests a functional significance. ORs are disposed on all human chromosomes except 20 and Y, and nearly 80% are found in clusters of 6-138 genes. A novel comparative cluster analysis was used to trace the evolutionary path that may have led to OR proliferation and diversification throughout the genome. The results of this analysis suggest the following genome expansion history: first, the generation of a "tetrapod-specific" Class II OR cluster on chromosome 11 by local duplication, then a single-step duplication of this cluster to chromosome 1, and finally an avalanche of duplication events out of chromosome 1 to most other chromosomes. The results of the data mining and characterization of ORs can be accessed at the Human Olfactory Receptor Data Exploratorium Web site (http://bioinfo.weizmann.ac.il/HORDE).

Predictions of gene family distributions in microbial genomes: evolution by gene duplication and modification.

A universal property of microbial genomes is the considerable fraction of genes that are homologous to other genes within the same genome. The process by which these homologues are generated is not well understood, but sequence analysis of 20 microbial genomes unveils a recurrent distribution of gene family sizes. We show that a simple evolutionary model based on random gene duplication and point mutations fully accounts for these distributions and permits predictions for the number of gene families in genomes not yet complete. Our findings are consistent with the notion that a genome evolves from a set of precursor genes to a mature size by gene duplications and increasing modifications.

Cognitive dysfunction in recovered depressive patients with silent cerebral infarction.

In this study, we characterized cognitive functioning in patients with major depression and silent cerebral infarction (SCI), as detected by magnetic resonance imaging (MRI), after they had recovered from depression. Thirty-five patients with unipolar depression who experienced the onset of depression after the age of 50 underwent MRI and were classified as SCI(+) (n = 17) or SCI(-) (n = 18). The Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Uchida-Kraepelin psychodiagnostic test were administered after the patients had recovered from depression. In addition, the intelligence quotient (IQ) and mental speed of the patients in the two groups were compared. The total, verbal and performance IQ scores, as determined by the WAIS-R, were significantly lower in the SCI(+) group than in the SCI(-) group. The mental speed of patients in the SCI(+) group, as assessed by the Uchida-Kraepelin psychodiagnostic test, was almost half that of the SCI(-) group. Our findings provide further evidence that a comprehensive impairment of cognitive functioning, especially a severe reduction in mental speed, remains after recovery from depression in patients with major depression and SCI.

Clinical features and treatment response of patients with major depression and silent cerebral infarction.

Previously, we reported a relationship between silent cerebral infarction (SCI), as detected by magnetic resonance imaging (MRI), and late onset major depression. In the present study, we clarify the clinical features of the depressive phase of patients with major depression and SCI, and their response to antidepressant pharmacotherapy. Using clinical charts, we retrospectively examined patients with depression, who were first admitted for antidepressant pharmacotherapy. All patients were classified according to the MRI findings and the age on admission (older or younger than 50 years) into either the young SCI(-) group (n = 23), the elderly SCI(-) group (n = 27) or the elderly SCI(+) group (n = 20).The characteristics of the clinical features were evaluated at the time of admission, after 2 weeks of treatment and at the time of discharge using the Hamilton rating scale for depression (HAMD). These data were compared between each patient group. No differences in the clinical features, as evaluated by HAMD, were observed between the three groups at the time of admission. However, the mean length of treatment was significantly longer and the treatment response, as evaluated by the total HAMD score, was significantly worse in the elderly SCI(+) group than in the other two groups, when examined after 2 weeks of treatment and at the time of discharge. The elderly SCI(+) group demonstrated higher scores in feelings of guilt, suicide, retardation and hypochondriasis than the young SCI(-) group and the elderly SCI(-) group after two weeks of treatment, and higher scores in early insomnia, late insomnia, somatic anxiety and hypochondriasis at the time of discharge. Our findings suggest that while the presence of SCI does not affect the clinical features observed at the time of admission, it does affect the treatment response to antidepressant pharmacotherapy.

Effectiveness of valproate on delirium and/or aggressive behavior in demented patients: A practical pilot study.

This open study was designed to evaluate the efficacy of valproate as a treatment for delirium and/or aggressive behavior in patients with dementia. Of the patients who participated, nine had vascular dementia, two had Alzheimer's disease, one had Parkinson's disease and one had alcohol dependence, all meeting DSM-IH-R criteria for dementia. In these 13 patients, delirium in seven and aggressive behavior in 12 patients were the target symptoms of this study. Valproate was administered orally at a dose of 200-600 mg daily (mean 526 mg, sd=20.4) without changing the dose of the other medications. The effect of valproate on delirium and aggressive behavior was evaluated with the Delirium Rating Scale (DRS) and Gottfries-Brane-Steen Scale (GBS). The total DRS scores decreased in 6/7 patients with delirium (P < 0.05) within 2 weeks. There were significant diferences between the score variances (before and during treatment) of the three categories in the GBS scale: emotional lability (P < 0.01), irritability (P < 0.01) and restlessness (P < 0.01). These findings suggest the effectiveness of valproate treatment for delirium and/or aggressive behavior in demented patients.

Atrial infarction leading to rupture.

In the case described, necrosis of the atrial musculature led to rupture of the chamber. This was overlooked for 4 days until the patient died of ventricular rupture. This unusual complication of atrial infarction may be amenable to surgical repair if recognised in time. The high gain recording of P waves in the presence of AV block made it possible to evaluate the P wave changes during atrial infarction: (1) changes in the configuration and width of the P wave, probably resulting from intra-atrial conduction defect; (2) depression of the PR segment (0.04 to 0.07 mV); and (3) a previously unrecorded convexity in the first portion of the PR segment, in the leads in which the depression of the PR segment was observed.