Pharmacokinetic studies on aztreonam in late pregnancy in sheep and humans

The transplacental passage of single intravenous doses of aztreonam (AZT), 1 g or 2 g, was examined in 7 sheep and 14 women in late pregnancy, respectively and the obtained data were analyzed by a two-compartment model. The obtained results were summarized as follows. After single 2 g intravenous doses were given to pregnant sheep, the mean peak level of AZT in maternal blood was 83.79 micrograms/ml and the half-life of the beta-phase was 1.525 hours. After single 1 g intravenous doses were administered to pregnant women, the mean peak level of AZT in blood was 102.62 micrograms/ml and the half-life of beta-phase was 2.128 hours. The peak levels in umbilical venous blood and amniotic fluid were 14.43 micrograms/ml and 11.86 micrograms/ml, respectively.     

Morphologic analysis of rat retinocollicular neuron terminals containing monoamine oxidase

The retino-collicular neuron terminals containing type A monoamine oxidase (MAO-A) in the stratum griseum superficiale of the rat superior colliculus were analyzed to provide a morphologic basis for the physiologic role of these neurons in the visual pathway. A computer-assisted, three-dimensional re-construction of the terminal complex associated with the MAO-A-positive terminals was performed. MAO-A-positive terminals originated in the retina and terminated in the stratum griseum superficiale. This was confirmed by tract tracing and enucleation experiments. The terminals were densely grouped in clusters of irregularly shaped swellings. Electron microscopy revealed that the MAO-A-positive terminals were located in a glomerulus-like structure. In this terminal complex, a significant proportion of the axonal profiles (42.96%) synapsed with the MAO-A-positive terminals. Most of the profiles (24.16%) resembled presynaptic dendrites, which represent intermediate elements between the retinal terminals and conventional dendrites. Unlike the glomerulus in the dorsal lateral geniculate body, the MAO-A-positive terminal swellings were not located in the central part of the terminal complex. The terminals had an irregular shape and were located in the complex. The terminal complex was partially ensheathed by glial processes. Furthermore, the membrane surfaces exhibiting synaptic specializations were very small compared with the total surface of the terminal swellings. The membrane length of the synaptic specialization was 5.38% of the total perimeter of the MAO-A-positive terminals.     

Potential doubling time and tumour doubling time in meningiomas and neurinomas

Summary Cell kinetic study plays an important role in treatment planning of brain tumour patients. MIB-1 antibody has recently become available, which detects Ki-67 antigen even in the formalin-fixed paraffin-embedded specimens. We performed MIB-1 immunostaining in 50 meningiomas and 50 neurinomas, and estimated the cell cycle time (tc) and potential doubling time (Tpot) from MIB-1 staining index (MIB-1 SI) and mitotic index (MI). MIB-1 SI logarithmically correlated with MI in both meningiomas and neurinomas. The tc and the Tpot were expressed as a function of the mitosis time (tm), while the tm is known to be around one hour and not exceeding two hours. When the tm was assumed to be one hour, the average tcs of meningiomas and neurinomas were 6.53±3.56 days and 7.67±3.27 days, respectively. The Tpots were447 × (MIB-1 SI)^–1.29 × tm in meningiomas, and490 × (MIB-1 SI) ^–0.98 × tm in neurinomas.The tumour doubling times (Tds) were calculated from serial imaging studies in 22 neurinomas and 15 meningiomas. The Tds were formulated as794 × (MIB-1 SI) ^–0.83 in meningiomas and1380 × (MIB-1 SI) ^–0.97 in neurinomas. Most of the Tds correlated well with the Tpots in meningiomas and neurinomas, and exceeded values of the Tpot when the tm is assumed to be one hour, although a few tumours showed unexpectedly longer Tds. The Tpot and the tc estimated from MIB-1 SI and MI are clinically useful parameters for predicting the growth potential of meningiomas and neurinomas where no other simple methods are available.     

Analysis of Responsive Cells in Tolerance by the Oral Administration of Ovalbumin

The induction of immune tolerance is the most common consequence of protein feeding, i.e., “oral tolerance”. In this study we investigated the genetic basis of oral tolerance using various kinds of recombinant and congenic mice, and the cells involved in the development of this phenomenon in mice. The footpad swelling response to ovalbumin (OVA) was inhibited in mice that were orally fed OVA 7 days before sensitization. No effect of strain of mouse was seen in this inhibition. This inhibition could be transferred by Peyer's patch cells. The CD4^-8⁺ T cells were responsible for the inhibition of footpad swelling. The number of CD4⁺ cells from OVA-fed tolerant mice decreased significantly, but CD8⁺ cells did not.

The number of CD4^-8⁺ T cells was increased in Peyer's patches of OVA-fed tolerant mice, and were involved in the development of oral tolerance.     

Perspectives on the Mechanism of Action of Electroconvulsive Therapy: Anticonvulsant, Peptidergic, c-fos Proto-oncogene Effects

Although the mechanism of action of electroconvulsive therapy (ECT) in affective illness has remained elusive, it is hoped that the consideration of mechanisms underlying the anticonvulsant efficacy of ECT will provide new insights into its biochemical and neuroanatomical substrates. In the amygdala-kindling model, electroconvulsive seizures (ECS) inhibit both the development and completed phases of kindled seizure evolution, and therefore, ECS is a more potent anticonvulsant modality than carbamazepine, which inhibits only completed kindled seizures. Carbamazepine is increasingly recognized for its acute and prophylactic efficacy in bipolar affective illness. Thus, comparing and contrasting effects of ECS and carbamazepine may provide insights into overlapping mechanisms of anticonvulsant and psychotropic action. Anticonvulsant effects of ECS have been most closely linked to endogenous opiate substances, perhaps acting on delta-opiate receptors, but a wide variety of other neurotransmitter and peptidergic effects are also potential candidates. Electroconvulsive seizures in mice activate the proto-oncogene c-fos in many discrete areas of brain, including a variety of limbic sites, the ventromedial nucleus of the hypothalamus, and the cerebellum. As such, c-fos induction may provide both an anatomical map of areas potentially activated by ECS and a potential mechanism for initiating a sequence of events that may be important to the mechanism of action of ECT. Although the anticonvulsant effects of ECT may ultimately prove to be separable from those mediating its therapeutic effects in affective illness, seizures and anticonvulsant effects provide easily measurable endpoints for preclinical and clinical studies. Given this clarity of effect, potential anticonvulsant mechanisms can rapidly be identified, enabling direct testing of whether or not these same mechanisms are also critical to the therapeutic effects of ECT in affective illness.     

Ground-glass hepatocytes in fibrinogen storage disease in Japanese Black calves

This paper reports the occurrence of large intracytoplasmic inclusions observed in the hepatocytes of six Japanese Black calves showing clinical illness. These inclusions were round to elongated polyhedral in shape, with a consistently homogeneous glassy appearance. Hepatocytes with the inclusions had a ground-glass appearance. The inclusions were negative for the periodic acid-Schiff reaction and methenamine silver stain. Immunohistochemically, they were strongly positive for fibrinogen. Electron microscopy revealed that the inclusions consisted of granular material, showing moderate electron density and bounded by a unit membrane. On the external surface of the unit membrane, there were direct connections to cellular organelles, including the ribosomes and rough-surfaced endoplasmic reticulum. The results showed these inclusions to be entirely consistent with fibrinogen inclusions described in man. Hepatocellular fibrinogen storage disease, as identified in this study, has not previously been described in animals.     

Three TNFalpha single nucleotide polymorphisms in the Japanese population

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) is an essential regulator of immune responses and is implicated to relate to several types of disease susceptibilities. Population information on polymorphisms is essential for the study of genetic diseases. AIM: To obtain accurate information about single nucleotide polymorphisms (SNPs) in the TNFalpha gene in the Japanese population. SUBJECTS AND METHODS: The entire TNFalpha gene was screened for SNPs by directly sequencing 48 chromosomes derived from 24 unrelated Japanese individuals. Allele frequencies of each polymorphism were determined and compared with those previously reported in other populations. RESULTS: Three SNPs, -308G/A at nt -308, IVS1 + 125G/A at nt 492 and IVS3 + 104G/A at nt 1359 were observed, of which one (IVS3 + 104G/A at nt 1359) was novel. In addition, allele frequencies of -308G/A were remarkably different from those presented in the NCBI dbSNP, indicating a significant ethnic difference. CONCLUSIONS: The polymorphisms and allele frequencies obtained in this study will be useful for genetic studies of common diseases such as osteoporosis and rheumatoid arthritis in the Japanese population.     

Nine-bp repeat polymorphism in exon 1 of thehMSH3 gene

Summary We have identified a polymorphic 9-bp repeat sequence in exon 1 of thehMSH3 gene using polymerase chain reaction (PCR). Five alleles were observed in unrelated Japanese individuals with heterozygosity of 0.57.