Infantile osteopetrosis; bone marrow transplantation from a cousin donor

The successful correction of infantile osteopetrosis in an Asian child by bone marrow transplantation (BMT) from an HLA-A,B matched cousin donor is reported. Retrospective HLA molecular analysis revealed that patient and donor were incompatible for HLA-DPB1. Donor type cells detected in the patient after transplantation indicate successful engraftment. The patient is currently alive and well.     

Vascular plasticity in cerebrovascular disorders

Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.     

Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators

Apoptosis (Ao), is a process by which cells undergo a form of nonnecrotic cellular suicide. Although for most cells this is a constitutive process, it can be induced in immature and differentiating immune cell populations by stress mediators associated with inflammation. This inducible form of A(o) is referred to as programmed cell death. However, it is not clear whether hematopoietic cell populations such as the thymus and bone marrow are induced to undergo A(o) during polymicrobial sepsis. To assess this, thymocytes, bone marrow cells, or splenocytes (as a source of comparative nonhematopoietic cells) were harvested from C3H/HeN mice at 1, 4, or 24 hours after cecal ligation and puncture (CLP; to induce polymicrobial sepsis) or sham-CLP (Sham). The results showed that mixed bone marrow cells ex vivo, although not to the same extent as thymus, showed a marked increase in the percentage of cells in A(o), increased endonuclease activity, and a significant decrease in cell yield at 24 hours but not at 4 hours after CLP. Similar changes were not evident in splenocytes. Phenotypic, as well as morphologic assessment, indicated that most of the increase in apoptotic cells in the thymus was associated with the immature T cells (CD4+CD8+) and CD8-CD4- cells. In contrast, the increase in bone marrow cell A(o) was associated with only the B220+ cells, with no significant contribution from myeloid cells. Treatment of CLP mice in vivo with either RU-38486 or PEG-(rsTNF- R1)2 was unable to reverse the increased A(o) in the bone marrow of these animals. Taken together, these findings indicate that A(o) as a process induced by polymicrobial sepsis is not limited to the thymus, but can also be detected in the bone marrow. However, unlike thymic A(o), bone marrow is not affected directly/indirectly by glucocorticoids or tumor necrosis factor released during sepsis.     

Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England

Summary.  An H1N7 influenza A virus, isolated from pigs in England in 1992, was examined genetically to determine the characteristics and probable origin of the eight gene segments. Six of the RNA segments encoding PB2, PB1, PA, HA, NP and NS were related most closely to those of human viruses, whilst two of the RNA segments (NA and M) were related most closely to those of equine viruses. The HA gene was most similar to that of A/USSR/90/77 (H1N1) but amino acid differences suggested independent genetic drift. In contrast, there were relatively few changes in the NA and M genes compared to those of A/equine/Prague/1/56 (H7N7). Accepted November 12, 1996 Received November 12, 1996     

Topographic specificity of functional connections from hippocampal CA3 to CA1

The hippocampus is a cortical region thought to play an important role in learning and memory. Most of our knowledge about the detailed organization of hippocampal circuitry responsible for these functions is derived from anatomical studies. These studies present an incomplete picture, however, because the functional character and importance of connections are often not revealed by anatomy. Here, we used a physiological method (photostimulation with caged glutamate) to probe the fine pattern of functional connectivity between the CA3 and CA1 subfields in the mouse hippocampal slice preparation. We recorded intracellularly from CA1 and CA3 pyramidal neurons while scanning with photostimulation across the entire CA3 subfield with high spatial resolution. Our results show that, at a given septotemporal level, nearby CA1 neurons receive synaptic inputs from neighboring CA3 neurons. Thus, the CA3 to CA1 mapping preserves neighbor relations.     

Control of carcinoid syndrome with hepatic artery embolization

Eighteen patients with metastatic carcinoid were treated by hepatic artery embolization with Gelfoam or polyvinyl alcohol foam for control of the carcinoid syndrome. Seventeen showed subjective or objective clinical improvement, including less skin flushing, diarrhea, and bronchospasm. Fourteen showed improvement in biochemical indices, including decreased urinary 5-hydroxyindoleacetic acid levels. The mean life span of the treated patients from the first episode of flushing to the time of this report was 5.4 years, and half of the patients are still alive. This survival time compares favorably with previous reports of survival of 3.2 years from the onset of flushing.