Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer.

BACKGROUND: There are few effective approaches to infertile patients with repeated failure in IVF-embryo transfer therapy. Since recent evidence suggests that some populations of maternal immune cells positively support embryo implantation, we have developed a new approach using peripheral blood mononuclear cells (PBMCs). METHODS: Patients who had not experienced successful pregnancy despite four or more IVF-embryo transfer sessions were enrolled in this study (n = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly isolated from patients again, combined with cultured PBMC and then administered to the intrauterine cavity of the patients. Blastocyst transfer was performed on day 5, and the success of implantation in the PBMC-treated group was compared with that in the non-treated group. RESULTS: Clinical pregnancy rate, implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and 35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively). CONCLUSION: Intrauterine administration of autologous PBMC may be an effective approach to improve embryo implantation in patients with repeated IVF failures.

Characterizing the new transcription regulator protein p60TRP.

Active cell death ('apoptosis' or 'programmed cell death') is essential in the development and homeostasis of multicellular organisms and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death might be implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using bioinformatics-, Western-blotting-, yeast-two-hybrid-system-, polymerase chain reaction (PCR)-, and fluorescence microscopy-analyses, we demonstrate here that the neuroprotective protein p60TRP (p60-transcription-regulator-protein) is a basic helix-loop-helix (bHLH) domain-containing member of a new protein family that interacts with the Ran-binding-protein-5 (RanBP5) and the protein-phosphatase-2A (PP2A). The additional findings of its influence on NNT1 and p48ZnF (new-neurotrophin-1, p48-zinc-finger-protein)-signaling and its down-regulation in the brain of AD subjects point to a possible pivotal role of p60TRP in the control of cellular aging and survival.

Alterations of muscarinic acetylcholine receptor subtypes in diffuse lewy body disease: relation to Alzheimer's disease.

OBJECTIVES: Dementia associated with Lewy bodies in cortical and subcortical areas is classified as dementia of the non-Alzheimer type and termed diffuse Lewy body disease (DLBD). The generic term "dementia with Lewy bodies (DLB)" was proposed in the international workshop on Lewy body dementia to include the similar disorders presenting Lewy bodies. In DLB, a lower level of choline acetyltransferase (ChAT) activity in the neocortex was found compared with that in Alzheimer's disease. The purpose of the present study was to determine the total amount of muscarinic acetylcholine receptors (mAChRs) and relative proportion of each subtype (m1-m4) of mAChRs in the frontal and temporal cortex of seven DLBD and 11 Alzheimer's disease necropsied brains. METHODS: A [(3)H]quinuclidinyl benzilate (QNB) binding assay and an immunoprecipitation assay using subtype-specific antibodies were performed. Each antibody was raised against fusion proteins containing peptides corresponding to the third intracellular (i3) loops of the respective mAChR subtype. RESULTS: The total amounts of mAChRs were significantly lower in the preparations of temporal cortices from DLBD and Alzheimer's disease than in those from dead controls (seven cases). In both diseases, the proportion of the m3 receptor in the frontal cortex was significantly increased and that of the m4 receptor in the temporal cortex was significantly decreased compared with the control specimens. The proportions of the m1 and m2 subtypes were significantly different in the temporal cortex. The proportion of the m1 receptor was significantly greater in the DLBD brains, whereas that of the m2 receptor was significantly greater in the Alzheimer's disease brains than in the controls. CONCLUSIONS: The m1 receptor is the major subtype in the cerebral cortex, and m2 is known to be present at presynaptic terminals. The higher proportions of m1 in DLBD and m2 in Alzheimer's disease suggest that the manner of degeneration in the cholinergic system is different between the diseases. It is hypothesised that a severe depletion of presynaptic cholinergic projective neurons causes the upregulation of m1 receptor in the temporal cortex in DLBD.

Parvalbumin-immunoreactive neurons in the cortex in Pick's disease.

Parvalbumin (a calcium-binding protein)-immunoreactive (PV-Ir) neurons in the cerebral cortex were examined in 20 postmortem brains obtained from elderly controls and patients with Pick's disease (PD). The type of PV-Ir neurons and their distribution in control and PD brains were similar. The number of PV-Ir neurons in PD brains did not differ significantly from that in the control brains either. These findings suggested that PV-Ir neurons in the cortex are not affected in PD brains. A significant loss of PV-Ir neurons has already been reported in brains obtained from patients with Alzheimer-type dementia (ATD), and the present results suggest the possibility that the damage of PV-Ir neurons might be comparatively selective for ATD brains.

Association of hypercalcemia with tumors producing colony-stimulating factor(s).

Two human malignant tumors, which we previously reported to produce colony-stimulating factors (CSFs), were found to be accompanied by remarkable hypercalcemia. A patient with a CSF-producing lower jaw cancer (squamous cell carcinoma) developed a marked granulocytosis (150,000/microliters) and hypercalcemia (more than 215 mg/dl). The tumor was successfully transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and hypercalcemia (20 mg/dl). White blood cell and serum calcium concentrations of these mice decreased promptly to normal levels when the tumor was excised. Treatment with prednisolone (1.5 mg/kg) or indomethacin (5 mg/kg) had no effect on the serum calcium level of these mice. Parathyroid hormone or prostaglandin E was not increased in the serum of the mice or in the tumor tissue. However, the mice bearing the tumor excreted extremely large amounts of calcium in their urine, and their bony tissues contained less calcium and phosphorus than controls. Moreover, histology of bony tissues of these nude mice clearly demonstrated the decrease in trabecular tissues and cortical thickness as well as remarkable activation of osteoclasts. Another patient with a CSF-producing bronchogenic squamous cell carcinoma showed mild granulocytosis and hypercalcemia. The biopsied tumor tissue was transplanted into nude mice, which developed marked granulocytosis (300,000/microliters) and also severe hypercalcemia (18 mg/dl). These results suggest the presence of a new syndrome of granulocytosis and hypercalcemia associated with CSF-producing tumors. The causal mechanism of the hypercalcemia was shown to be some humoral factor which activates osteoclasts other than parathyroid hormone. Neither prostaglandins nor osteoclast-activating factor seemed to be the cause of the hypercalcemia.

System degeneration of the thalamus. A clinico-neuropathological study.

A case of essential degeneration of the thalamus is reported. The patient was a 43-year-old Japanese male, who, a few weeks after mild head trauma, suffered from forgetfulness, psychomotor slowing, and Korsakoff's syndrome. Four to five months later, there were optical hallucinations and delirium and he died 19 months after the onset of symptoms. Neuropathological examination revealed symmetrical thalamic degeneration, whose distribution corresponded to phylogenetically younger subunits of the thalamus. In addition, there was olivovermian degeneration. These findings are identical to those of eleven cases hitherto reported. Five of these were Japanese, including the present one. The syndrome thalamic degeneration may now be classified as a special type of "system degeneration".

Insulin receptor function and insulin effects on glucose metabolism in adipocytes from ventromedial hypothalamus-lesioned rats.

To investigate the mechanism of the development of insulin resistance in hypothalamic obesity, we studied insulin binding, glucose transport, and glucose oxidation in adipocytes from ventromedial hypothalamus (VMH)-lesioned rats 1 and 2 weeks after injury. One week after injury, insulin binding and insulin-stimulated glucose oxidation were increased, but insulin-stimulated glucose transport was similar to control. Two weeks after injury, insulin binding and insulin-stimulated glucose transport were similar to control, but insulin-stimulated glucose oxidation was decreased. Thus, cellular insulin responsiveness was increased in adipocytes from VMH-lesioned rats 1 week after injury; this increase in insulin responsiveness was due mainly to the increased intracellular glucose metabolism. On the other hand, cellular insulin resistance existed in adipocytes from VMH-lesioned rats 2 weeks after injury; this insulin resistance was also due mainly to a defect in intracellular glucose metabolism.

Serum 25-hydroxyvitamin D and vitamin D-binding protein levels and mineral metabolism after partial and total gastrectomy.

The effects of gastrectomy, especially total gastrectomy, on the serum levels of 25-hydroxyvitamin D and vitamin D-binding protein and on mineral metabolism were examined. The serum 25-hydroxy-vitamin D levels were markedly decreased in patients with total gastrectomy and Billroth II gastrectomy. Decreased levels of serum vitamin D-binding protein and serum calcium, and increased levels of serum alkaline phosphatase were observed in both patients with partial gastrectomy and patients with total gastrectomy. The results show that vitamin D deficiency could develop in high frequency patients with total gastrectomy and Billroth II gastrectomy, and that deranged mineral metabolism could develop in patients with any type of gastrectomy with or without vitamin D deficiency. The decreased levels of serum vitamin D-binding protein in postgastrectomy patients may be a sensitive reflection of the failure of hepatic protein synthesis.

Dementia-Parkinsonism syndrome with numerous Lewy bodies and senile plaques in cerebral cortex.

Five cases of age range 62-72 years with progressive dementia and muscular rigidity are reported and discussed from the clinicopathologic point of view. The neuropathology of these cases was characterized by the widespread occurrence of Lewy bodies (LB) in the CNS as well as the presence of senile changes. The presence of numerous LB in the cerebral cortex and basal ganglia was especially characteristic, although their distribution pattern in the diencephalon and brain stem was identical to that found in paralysis agitans. On the other hand, the presence of senile changes in the cerebral cortex was almost identical to the neuropathology of senile dementia or Alzheimer's disease. Nosologically, the present cases may represent either a combination of atypical paralysis agitans with senile dementia and Alzheimer's disease, or a new disease.

[Amyotrophic lateral sclerosis with degeneration of thalamus and substantia nigra (author's transl)]. / Myatrophische Lateralsklerose kombiniert mit Degeneration im Thalamus und der Substantia nigra.

A 40-year-old man suffering from amyotrophic lateral sclerosis with symmetrical degeneration of the thalamus and the substantia nigra is reported. The distribution pattern of the thalamic degeneration in the present case was characteristic in that the Nucleus centralis was the severest affected of the thalamic nuclei. As far as we know, there is no such case of amyotrophic lateral sclerosis in the literature. Nosologically, this case may represent a form of combined heredosystemic degeneration.

Multiple system degeneration and involving thalamus, reticular formation, pallido-nigral, pallido-luysian and dentato-rubral systems. A case report.

An autopsy case of multiple system degeneration is characterized by the following; (1) progressive dementia and abnormal sleep patterns, followed by Parkinsonian symptoms with terminal akinetic mutism; (2) severe symmetrical degeneration in the thalamus, particularly nucl. medialis thalami, the reticular formation of the brain stem, also the pallidonigral, pallido-Luysian and dentato-rubral systems. As far as we known, there is no case in the literature, of combined system degeneration, which shows such a wide anatomical range of lesions as the present one. Clinico-pathological correlation between dementia and degeneration of the thalamus, and between abnormal sleep-consciousness mechanism and degeneration of the reticular formation are discussed. The extrapyramidal symptoms are discussed from the clinico-pathological aspect. In addition, peculiar eosinophilic bodies are described, which were most frequently found in the putamen.

Cell wall of Mycobacterium lepraemurium strain Hawaii.

The chemical properties of the cell wall of Mycobacterium lepraemurium strain Hawaii were investigated. Five subunits of the cell wall, arabinose mycolate, mycolic acids, tetrapeptide (Ala-Gln-diaminopimelic acid-Ala), disaccharide (N-acetylglucosaminyl-beta-1,4-N-glycolylmuramic acid), and arabinogalactan, were obtained, and their chemical structures were identified.