Parasympathetic brainstem origin sites of triggered external and internal carotid vasodilation are not distributed topographically in the rat.

Cranial parasympathetic activation produces vasodilation in the head and neck region, but little is known about its central and peripheral mechanisms. This study was conducted to examine whether external and internal carotid-vasodilation origin sites triggered by chemical stimulation are distributed topographically in the parasympathetic brainstems of anesthetized rats, and to examine the effects of peripheral receptors on vasodilation. Microinjection of the neuromodulator candidate l-cysteine revealed that external and internal carotid vasodilation-triggering sites were distributed non-topographically along the full extent of the parasympathetic parvocellular reticular formation (PcRt).

An origin of carotid vasodilation extends along the full extent of the parasympathetic parvicellular reticular region in the rat brainstem.

During grooming in rats, cranial parasympathetic activation leads to increased carotid artery blood flow, but the brainstem origin of this vasodilation signal is poorly understood. The aim of this study was to map brainstem sites wherein chemical stimulation with l-cysteine, an ionotropic excitatory amino acid receptor activator, can trigger carotid vasodilation in anesthetized intact and superior cervical sympathectomized (SCD) rats. The right side of the brainstem was accessed ventrally; arterial blood pressure and right carotid artery flow resistance were monitored.

Topographic carotid vasoconstriction in the rostral ventrolateral medulla of rats.

The vascular beds of various cranial tissues receive common carotid flow, which contributes to blood flow redistribution associated with animal behaviors such as grooming, but the medullary autonomic regulation of carotid flow resistance (CAR) is poorly understood. This study is the first to examine the response sites of CAR in the rat rostral ventrolateral medulla (RVLM) presympathetic area to chemical stimulation by the ionotropic excitatory amino acid receptors activator L-cysteine. Arterial blood pressure and CAR were monitored in anesthetized rats which had a cranial window constructed above the ventral medulla.

Muscle vasodilator response via potential adrenaline secretion to L-cysteine microinjected in rostral ventrolateral medulla of rats.

We previously found that the thiol amino acid L-cysteine microinjected into rat medullary autonomic areas produces changes in arterial blood pressure (AP) via ionotropic excitatory amino acid receptors (iEAAr), but its effect on vascular beds is still unknown. Rostral ventrolateral medulla (RVLM) pressor area includes adrenal and lumbar presympathetic neurons which activation could cause opposite muscle vascular responses: vasodilation versus vasoconstriction. However, there are few data on the vasodilator response in rats.

Central cardiovascular actions of L-homocysteine microinjected into ventrolateral medullary autonomic areas of the rat.

Elevated L-homocysteine concentrations in the plasma and cerebrospinal fluid are related to cardiovascular and neuronal diseases, and could contribute to disease development. However, the central cardiovascular actions of L-homocysteine in two important autonomic regulating areas remain unknown: the rostral ventrolateral medulla (RVLM), including pre-sympathetic neurons, and the caudal ventrolateral medulla (CVLM), including interneurons projecting to pre-sympathetic neurons in the RVLM. Therefore, the aim of the current study was to examine the influence of L-homocysteine microinjected into the RVLM and CVLM areas on changes in arterial blood pressure (ABP) and heart rate (HR) of anesthetized rats, as well as the influence of ionotropic excitatory amino acid (iEAA) receptors on the central actions of L-homocysteine.

L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure.

The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors.

Cardiovascular actions of L-cysteine and L-cysteine sulfinic acid in the nucleus tractus solitarius of the rat.

The sulfur-containing excitatory amino acid (EAA) L-cysteine sulfinic acid (CSA), a neurotransmitter candidate, is endogenously synthesized from L-cysteine (Cys). Exogenous Cys administration into the brain produces cardiovascular effects; these effects likely occur via synaptic stimulation of central nervous system (CNS) neurons that regulate peripheral cardiovascular function. However, the cardiovascular responses produced by CNS Cys administration could result from CSA biosynthesized in synapse.

Functional cardiovascular action of L-cysteine microinjected into pressor sites of the rostral ventrolateral medulla of the rat.

The endogenous sulfur-containing amino acid L-cysteine injected into the cerebrospinal fluid space of the cisterna magna increases arterial blood pressure (ABP) and heart rate (HR) in the freely moving rat. The present study examined (1) cardiovascular responses to L-cysteine microinjected into the rostral ventrolateral medulla (RVLM), where a group of neurons regulate activities of cardiovascular sympathetic neurons and (2) involvement of ionotropic excitatory amino acid (iEAA) receptors in response. In the RVLM of urethane-anesthetized rats accessed ventrally and identified with pressor responses to L-glutamate (10 mM, 34 nl), microinjections of L-cysteine increased ABP and HR dose dependently (3-100 mM, 34 nl).

Pressor response to L-cysteine injected into the cisterna magna of conscious rats involves recruitment of hypothalamic vasopressinergic neurons.

The sulfur-containing non-essential amino acid L-cysteine injected into the cisterna magna of adult conscious rats produces an increase in blood pressure. The present study examined if the pressor response to L-cysteine is stereospecific and involves recruitment of hypothalamic vasopressinergic neurons and medullary noradrenergic A1 neurons. Intracisternally injected D-cysteine produced no cardiovascular changes, while L-cysteine produced hypertension and tachycardia in freely moving rats, indicating the stereospecific hemodynamic actions of L-cysteine via the brain.

Amino acids that centrally influence blood pressure and regional blood flow in conscious rats.

Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow.

Intracisternally injected L-proline activates hypothalamic supraoptic, but not paraventricular, vasopressin-expressing neurons in conscious rats.

When injected into specific rat brain regions, the neurotransmitter candidate L-proline produces various cardiovascular changes through ionotropic excitatory amino acid receptors. The present study used an immunohistochemical double-labeling approach to determine whether intracisternally injected L-proline in freely moving rats, which increases blood pressure, activates hypothalamic vasopressin-expressing neurons and ventral medullary tyrosine-hydroxylase- (TH-) containing neurons. Following injection of L-proline, the number of activated hypothalamic neurons that coexpressed vasopressin and c-Fos was much greater in the supraoptic nucleus (SON) than in the paraventricular nucleus (PVN) of rats with increased blood pressure.

The mapped pattern of kainate on blood pressure responses is similar to that of L-proline in the ventrolateral medulla of the rat.

Kainate is an excitatory amino acid receptor agonist with a structure similar to the amino acid L-proline. Our previous studies demonstrated that microinjections of L-proline into the ventrolateral medulla (VLM) of the rat induce a mapped pattern of blood pressure responses distinct from L-glutamate, and the depressor response to L-proline in the caudal VLM (CVLM) is abolished by the kainate/AMPA receptor antagonist CNQX. The present study investigated whether kainate produces the L-proline-mapped pattern of responses in the VLM, compared with the pattern by AMPA.

Antiproliferative effects of 5-fluorouracil and interferon-alpha in combination on a hepatocellular carcinoma cell line in vitro and in vivo.

Background And Aim: We investigated the antiproliferative effects of interferon-alpha (IFN-alpha) and 5-fluorouracil (5-FU) in combination on a hepatocellular carcinoma (HCC) cell line.

Method: In the in vitro study, IFN-alpha and/or 5-FU was added to the culture of the poorly differentiated-type HCC cell line, HAK-1B, and their antiproliferative effects and additional or synergic effects in combination treatment were examined. In the in vivo study, HAK-1B cells were transplanted into nude mice and the changes in tumor volume and weight, apoptosis, BrdU and cyclin A positive cells, and artery-like blood vessels were investigated.

Immunohistochemical evidence for the localization of neurons containing the putative transmitter L-proline in rat brain.

We examined whether there are the neurotransmitter candidate amino acid L-proline containing neurons localized in the rat brain. Antibodies against L-proline conjugated with rabbit serum albumin were raised in a rabbit and purified with affinity chromatography. Strong L-proline-like immunoreactivity was confined to several groups of neurons in the arcuate nucleus (n) and supraoptic n in the hypothalamus and area postrema.

Depressor responses to L-proline microinjected into the rat ventrolateral medulla are mediated by ionotropic excitatory amino acid receptors.

The essential amino acid L-proline produces a depressor response when microinjected into the caudal ventrolateral medulla (CVLM) of anesthetized rats. L-proline may activate some excitatory amino acid (EAA) receptors. The present study tested this hypothesis by investigating the effects of two ionotropic excitatory amino acid receptor antagonists on the depressor response to L-proline in the CVLM: the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the N-methyl-D-aspartate (NMDA) receptor-selective antagonist MK801.

Expression of matrix metalloproteinases (MMPs) in cultured hepatocellular carcinoma (HCC) cells and surgically resected HCC tissues.

Matrix metalloproteinases (MMPs) relate to the growth and infiltration of cancer cells, but the frequency and amount of their expression are not yet fully examined in hepatocellular carcinoma. Expression of MMPs (MMP-2, MMP-7, MMP-9, MT1-MMP, MT2-MMP, MT3-MMP) and tissue inhibitors of metalloproteinase (TIMP: TIMP-1, TIMP-2) was investigated on cultured hepatocellular carcinoma (HCC) cells and surgically resected HCC tissues. The cultured cells and tissues expressed MMPs and TIMPs at various degrees, and high expression was observed for MMP-2, MMP-9, MT1-MMP and TIMP-2.

Vasodilatation of the hindquarters induced by antagonism of GABA(A) receptors in the freely moving rat.

An intracisternal injection of the GABA(A) receptor antagonist bicuculline into conscious rats increased arterial pressure and decreased hindquarter resistance. Propranolol attenuated only the resistance response, but ganglionic block abolished both responses. These findings suggest that central GABA(A) receptor blockade induces an autonomic pressor action with hindquarter vasodilatation.

Antiproliferative effects of interferon-alphaCon1 on ovarian clear cell adenocarcinoma in vitro and in vivo.

Purpose: We examined the antiproliferative effect of IFN-alphaCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo.

Experimental Design: (a) The effects of IFN-alphaCon1 on growth, morphology, cell cycle, and type I IFN-alpha receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated.

Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo.

Background/aims: We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells.

Methods: The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined.

Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer.

Objectives: This study aimed to observe the expressions of Y box-binding protein-1 (YB-1) and P-glycoprotein (P-gp) in primary ovarian tumor and to determine whether they act as biomarkers for survival in epithelial ovarian cancer.

Methods: The expressions of YB-1 and P-gp were examined immunohistochemically in 59 patients who were treated from 1997 to 2000 at Kurume University Hospital. Samples were paraffin-embedded primary ovarian cancer tissue taken from the surgical specimens.

Intravenous leiomyomatosis with uterine leiomyoma and adenomyosis: a case presentation and brief comment on the histogenesis.

Uterine intravenous leiomyomatosis a rather rare pathologic condition, and a total of 139 cases have appeared in the English literature. Although two proposals for the histologic origin, uterine lyomyoma itself and/or vascular smooth muscle, have been widely accepted, the precise histogenesis still remains unclear. The additional 140th case of intravenous leiomyomatosis is described, and a third postulation for the histogenesis is proposed.

Primary leiomyoma of the ovary--a report of 2 resected cases.

Leiomyoma of the ovary is relatively rare and its origin is still controversial. Here, we report 2 cases of ovarian leiomyoma. Case 1, a 59-year-old woman who complained of abdominal distention.

Metastatic carcinoid tumor in the orbit.

In 1991, a carcinoid tumor of the duodenum with metastasis in the regional lymph nodes was resected in a 39-year-old-man. A metastasis in the mediastinum was found and was resected in 1996. In 1999, a metastasis in the left lung was discovered and was excised.

Hindquarters vasoconstriction through central GABA(B) receptors in conscious rats.

The exogenous application of GABA into the cisterna magna of the freely moving rat decreases hindquarters vascular tone as well as arterial pressure. GABA could influence GABA receptor subtypes A, B or C. However, the hindquarters vascular response to the stimulation of each receptor subtype has not yet been investigated.