The PBC domain contains a MEINOX domain: coevolution of Hox and TALE homeobox genes?

The diagnosis of inadequacy of the respiratory apparatus conditioning function (RACFI) necessitates carrying out an appreciable volume of calculations to determine observable and required values for its parameters, together with drawing up a concluding statement according to the existing RACFI classification. The above rapid method permits the 2.5-fold cut in man-power to be streamlined into research on respiratory heat-exchange in patients with cardiopulmonary disorders. The suggested method is recommended for use in therapeutic, pulmonological, cardiological departments and functional-diagnosis units in hospitals.     

Retinoids and Hox genes

The vertebrate embryonic body plan is constructed through the interaction of many developmentally regulated genes that supply cells with the essential positional and functional information they require to migrate to their appropriate destination and generate the proper structures. Some molecular cues involved in patterning the central nervous system, particularly in the hindbrain, are interpreted by the Hox homeobox genes. Retinoids can affect the expression of Hox genes in cells lines and embryonic tissues; the hindbrain and branchial region of the head are particularly sensitive to the teratogenic effects of retinoic acid. The presence of endogenous retinoic acid, together with the distribution of retinoid binding proteins and nuclear receptors in the developing embryo, strongly suggest that retinoic acid is a natural morphogen in vertebrate development. The molecular basis for the interaction between retinoic acid and the Hox genes has been aided in part by approaches using deletion analysis in transgenic mice carrying lacZ reporter constructs. Such studies have identified functional retinoic acid response elements within flanking sequences of some of the most 3' Hox genes, suggesting a direct interaction between the genes and retinoic acid. Furthermore, as demonstrated using transgenic mice carrying Hoxb-1/lacZ constructs, multiple retinoic acid response elements may cooperate with positive and negative regulatory enhancers to specify pattern formation in the vertebrate embryo. These types of studies strongly support the normal roles of retinoids in patterning vertebrate embryogenesis through the Hox genes.     

Hox9 genes and vertebrate limb specification

Development of paired appendages at appropriate levels along the primary body axis is a hallmark of the body plan of jawed vertebrates. Hox genes are good candidates for encoding position in lateral plate mesoderm along the body axis and thus for determining where limbs are formed. Local application of fibroblast growth factors (FGFs) to the anterior prospective flank of a chick embryo induces development of an ectopic wing, and FGF applied to posterior flank induces an ectopic leg. If particular combinations of Hox gene expression determine where wings and legs develop, then formation of additional limbs from flank should involve changes in Hox gene expression that reflect the type of limb induced. Here we show that the same population of flank cells can be induced to form either a wing or a leg, and that induction of these ectopic limbs is accompanied by specific changes in expression of three Hox genes in lateral plate mesoderm. This then reproduces, in the flank, expression patterns found at normal limb levels. Hox gene expression is reprogrammed in lateral plate mesoderm, but is unaffected in paraxial mesoderm. Independent regulation of Hox gene expression in lateral plate mesoderm may have been a key step in the evolution of paired appendages.     

Homeobox genes in hematopoiesis and leukemogenesis

The effect of cold and warm intermittent antegrade blood cardioplegia, on the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery, was investigated. Intracellular taurine was measured in ventricular biopsies taken before institution of cardiopulmonary bypass, at the end of 30 min of ischaemic arrest and 20 min after reperfusion. There was no significant change in the intracellular concentration of taurine in ventricular biopsies taken after the period of myocardial ischaemia in the two groups of patients (from 10.1 +/- 1.0 to 9.6 +/- 0.9 mumol/g wet weight for cold and from 9.3 +/- 1.3 to 10.0 +/- 1.3 mumol/g wet weight for warm cardioplegia, respectively). Upon reperfusion however, there was a fall in taurine in both groups but was only significant (P < 0.05) in the group receiving cold blood cardioplegia (6.9 +/- 0.8 mumol/g wet weight after cold blood cardioplegia versus 8.0 +/- 0.8 mumol/g wet weight following warm blood cardioplegia). Like taurine, there were no significant changes in the intracellular concentration of ATP after ischaemia in the two groups of patients (from 3.2 +/- 0.32 to 2.95 +/- 0.43 mumol/g wet weight for cold and from 2.75 +/- 0.17 to 2.62 +/- 0.21 mumol/g wet weight for warm cardioplegia, respectively). However upon reperfusion there was a significant fall in ATP in both groups with the extent of the fall being less in the group receiving warm cardioplegia (1.79 +/- 0.19 mumol/g wet weight for cold and 1.98 +/- 0.27 mumol/g wet weight for warm cardioplegia, respectively). This work shows that reperfusion following ischaemic arrest with warm cardioplegia reduces the fall in tissue taurine seen after arrest with cold cardioplegia. Accumulation of intracellular sodium provoked by hypothermia and a fall in ATP, may be responsible for the fall in taurine by way of activating the sodium/taurine symport to efflux taurine.     

The role of homeobox genes in limb development

Intensive study of the development of the vertebrate limb has led to a conceptual framework for understanding the specification of a limb primordium, the outgrowth of those cells and their organization and differentiation into a functional appendage. During the past few years, a number of homeobox-containing genes have been identified that are likely to play controlling roles in each of these events.     

Glucan as stimulator of hematopoiesis in normal and gamma-irradiated mice. A survey of the authors' results

Glucan, a beta-1,3-linked polyglucose derived from the yeast Saccharomyces cerevisiae, is a broad spectrum enhancer of host defense mechanisms stimulating humoral and cell-mediated immunity. On the basis of these features, glucan has been tested by the authors' research group in experiments on gamma-irradiated mice. Two glucan forms, particulate and soluble, have been studied. Attention has been focused on various application regimens in relation to the time of irradiation (pre- or postirradiation application), the possibilities of using glucan in various radiation regimens (single or repeated irradiation), combined pharmacological therapy (joint administration of glucan with cystamine or inhibitors of prostaglandin synthesis), and on the negative side effects of therapy with glucan. Some studies included also experiments on unirradiated mice. The results have demonstrated the ability of glucan to influence positively the course of the acute radiation disease. Stimulation of hematopoiesis has been found to be the most important mechanism of glucan's radioprotective effects. In this communication, the results of 11 full-length articles are summarized and discussed.     

The influence of recombinant human tumor necrosis factor alpha and its muteins used alone or in combination with 2-chlorodeoxyadenosine on normal and leukemic hematopoiesis in vitro

We report an 80-year-old woman with progressive muscular atrophy predominantly involving her right lower extremity. She was well until 1992 (75 years of age) when she noted an onset of weakness in her right leg which had got progressively worse. She was admitted to our service in July 1994. On admission, general physical examination was unremarkable. She was alert and well oriented without dementia. Higher cerebral functions were normal. Cranial nerves also appeared intact. She dragged her right leg in walking. Mild to moderate weakness (2/5 to 4/5) was noted in muscles in her right lower extremity more in the distal part. Deep tendon reflexes were within normal limits, and the plantar response was flexor bilaterally. Sensation was intact. Laboratory examinations were also unremarkable except for slight increase in CK which was 470 IU/l. CSF was also normal. EMG revealed neurogenic changes in the lower extremities. She was admitted to Aoki Hospital on October 21, 1994, by that time, her weakness in the right lower extremity had gotten worse in that the muscle strength of the right extensor hallucis longus was 0 and tibialis anterior 2; muscle atrophy was also prominent in her right leg; the right ankle jerk could not be elicited. In the subsequent course, weakness and atrophy appeared in her left lower extremity, however, upper extremities and cranial nerves had never been affected. Babinski sign was always negative. In February 1996, she developed delusional ideation of self persecution, and showed difficulty in communication with medical staffs. She developed fever of 38.7 degrees C on June 13, 1996 expired on the next day. The patient was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had a form of spinal muscular atrophy. Opinions were divided between ALS and spinal muscular atrophy. Post-mortem examination revealed marked loss of anterior horn neurons in the lumbar area with astrogliosis. Bunina bodies were seen in some of the remaining neurons. No myelin pallor was noted in the pyramidal tracts, however, atrophy and loss of Betz cells were noted in the motor cortex. Other cortical areas were unremarkable. The neuropathologist arrived at the conclusion that the patient had ALS. This patient was unique in that she had asymmetric atrophy and weakness limited to the lower extremities. This is quite unusual as ALS of four years duration. In addition, the patient developed some mental change which was thought to represent dementia by some participants. But no clear morphologic changes were seen to account for her mental change.     

Expression of homeobox genes shows chelicerate arthropods retain their deutocerebral segment

Expression patterns of six homeobox containing genes in a model chelicerate, the oribatid mite Archegozetes longisetosus, were examined to establish homology of chelicerate and insect head segments and to investigate claims that the chelicerate deutocerebral segment has been reduced or lost. engrailed (en) expression, which has been used to demonstrate the presence of segments in insects, fails to demonstrate a reduced deutocerebral segment. Expression patterns of the chelicerate homologs of the Drosophila genes Antennapedia (Antp), Sex combs reduced (Scr), Deformed (Dfd), proboscipedia (pb), and orthodenticle (otd) confirm direct correspondence of head segments. The chelicerate deutocerebral segment has not been reduced or lost. We make further inferences concerning the evolution of heads and Hox genes in arthropods.     

Efficient adenovirus-mediated gene transduction of normal and leukemic hematopoietic cells

We evaluated the efficiency of adenovirus-mediated gene transfer into normal and malignant human hematopoietic cells. An E-1 and E-3 deleted, replication-defective recombinant Ad.RSV beta gal vector was used and the transduction efficiency was studied at a multiplicity of infection of 13 p.f.u. per cell. Approximately 40-50% of normal monocytes were transduced, whereas purified normal resting T cells and B cells were resistant to infection. We showed that 50-80% of primary chronic myeloid leukemia cells (CML, n = 12) were efficiently transduced in contrast to CML, successful transduction of resting primary chronic B lymphocytic leukemia cells required appropriate preactivation of targeted cells. A novel protocol for the efficient transduction of adenovirus into B-CLL cells was presented. We showed that anti-CD40 mAb or CD40 ligand acts in synergy with rhIL-4 to enable the transduction of approximately 50-75% of B-CLL cells (B-CLL, n = 6). Expression of beta-galactosidase in transduced CML cells and B-CLL cells was detected for at least 15 days after transduction. The present studies underline the utility of adenovirus vectors for the construction of cytokine gene-modified tumor vaccines for the treatment of hematopoietic malignancies such as CML and B-CLL.     

The cloning of fragments of homeobox genes expressed during planarian regeneration

The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WFQNRR) of the Antennapedia class homeodomain was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia-like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), were obtained. Their comparison with other homeobox genes using a "Genebee" software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily that includes mouse mesodermal homeobox genes Mox-1 and Mox-2 and rat homeobox gene Gax.     

Surface immunoglobulin on leukemic, leukemoid, and normal granulocytes

Using a new functional approach for the study of lymphomas and leukemias in which immunologic and cytochemical techniques were employed, we found a consistent surface immunoglobulin pattern of the gamma-, k-, lambda-type on cells from poorly differentiated (acute) and well-differentiated (chronic) granulocytic leukemias. This pattern was also found on nonneoplastic granulocytes from patients with leukemoid reactions as well as on granulocytes from normal individuals. These findings suggested that both leukemia cells and nonneoplastic granulocytes had IgG bound to the cell surface by an Fc receptor. This binding of IgG by granulocytes was not tumor-specific and appeared to correlate both with the degree of differentiation and possibly with the degree of activation of the granulocytes. In addition to raising the basic question of its functional significance, these findings offered an approach for distinction of poorly differentiated granulocytic leukemia from lymphomatous processes.     

Genetic interactions of Hox genes in limb development: learning from compound mutants

Some investigators have noted an increased incidence of suicidal ideation and attempts in individuals with panic attacks. The direct temporal relationship between the panic state and suicidal thoughts and behaviors has not been well elucidated however. Furthermore, although aggressive behavior is often manifested in individuals with suicidal behavior, the relationship between aggression and panic has received little attention. The aim of this study was to assess the frequency and type of reported suicidal and aggressive ideation and behaviors that occur during the panic state in patients with panic disorder. In order to evaluate the contribution of depression, individuals with pure (i.e. uncomplicated) panic disorder were compared with individuals who had comorbid panic and major depression. Nineteen patients with a diagnosis of pure panic disorder and 28 patients with comorbid panic plus major depression were included in the study. All patients were given the Panic, Suicide and Aggression Scale (PSAS), a questionnaire specifically designed to assess reported suicidal and aggressive thoughts and behaviors that occur during panic attacks. Other scales given to all patients included overall measures of impulsivity, suicide risk and violence risk. Patients with pure panic disorder reported high rates of suicidal and aggressive ideation and behavior during panic. The presence of comorbid depression resulted in a doubling of the rate of reported panic-associated suicidal ideation, property destruction and assaults, and a five-fold increase in the rate of homicidal ideation. The rate of reported suicide attempts was equal in the pure panic and comorbid group. There were also high correlations in all panic patients between measures of panic-associated suicide and aggression with the psychometric measures of impulsivity, suicide risk and violence risk.