Branches of the splenic artery and splenic arterial segments

In 200 adult autopsy specimens, the arterial supply to the pancreas and spleen was studied radiologically and by manual dissection. The splenic artery divided into two or three lobar arteries, which supplied its corresponding lobe; each lobar artery subsequently divided into two to four lobular branches. Six to twelve lobular branches were observed entering the splenic substance at the hilum. Lobar arteries did not anastomose with each other, hence, the lobes of the spleen are also termed segments. The lobules, however, were not found to be independent segments and the arteries of one lobule anastomosed with those of other lobules. The branching pattern of the splenic artery varied from one specimen to another, so much so that a prevailing pattern could not be identified. Polar arteries, particularly to the superior pole, arose quite proximal to the hilum in 51% of cases and were occasionally missed. In 45% of males and 40% of females, the posterior gastric artery arose from about the middle of the splenic artery. The splenic artery was not found to be tortuous in fetuses, newborns, and young children. Tortuosity was seen in only 10% of adults; thus, the characteristic tortuosity of the splenic artery appears to develop with age.     

Estrogen effects on object memory and cholinergic receptors in young and old female mice.

We investigated whether object recognition memory is modulated by estrogen in young (5 month) and aged (24 month) female C57Bl/6J mice, and if cholinergic muscarinic receptors might contribute to this response. Mice that were ovariectomized, or ovariectomized plus estradiol-treated three weeks before behavioral testing or quantitative autoradiography were compared to intact mice. Memory for a previously encountered object deteriorated significantly between 3 and 6h after initial exposure, regardless of animal age. In both young and aged mice, estradiol-treated mice showed significantly greater recall than did ovariectomized mice. In both age groups, the apparent number of [(3)H]pirenzepine/M(1)-like and [(3)H]AFDX384/M(2)-like muscarinic receptor binding sites was reduced in the basal forebrain as well as its projection areas following ovariectomy, but this decrease was not alleviated by estrogen. Aging poorly affected object memory, but reduced muscarinic binding in some cortical subregions and in the caudate nucleus. These findings suggest that estrogen effects on memory in C57Bl/6J mice are not due to changes in the number of muscarinic receptors.     

Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices

1. The biphasic nature of the potent modulatory action of interleukin-2 (IL-2) on hippocampal acetylcholine (ACh) release was investigated by use of brain slice superfusion.
2. Both the potentiating (10⁻¹³ M) and inhibitory (10⁻⁹ M) effects of IL-2 on hippocampal ACh release were stimulation-dependent and were blocked by a neutralizing IL-2 receptor antibody, suggesting the activation of typical IL-2 receptors in both cases.
3. Tetrodotoxin (TTX; 10 μM) failed to block the potentiation of ACh release induced by a very low concentration of IL-2 (10⁻¹³M) suggesting a direct effect on cholinergic nerve terminals.
4. In contrast, the inhibitory effect seen at a higher concentration (10⁻⁹ M) was TTX-sensitive, and hence indicative of an indirect action.
5. To establish the nature of this intermediate mediator, blockers of nitric oxide synthesis, and of opioid and γ-aminobutyric acid (GABA) receptors were used. Only GABA_A and GABA_B receptor antagonists altered the inhibitory action of IL-2, suggesting the participation of GABA as mediator.
6. Taken together, these results provide further evidence for the potent role of IL-2 in the modulation of cholinergic function in the rat hippocampus.

     

Frequent Alterations of MCPH1 and ATM are Associated with Primary Breast Carcinoma: Clinical and Prognostic Implications

Background

MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.

Methods

To understand the importance of MCPH1 and ATM in deregulation of DNA damage response pathway in breast carcinoma, we studied m-RNA expression and genetic/epigenetic alterations of these genes in primary breast carcinoma samples.

Results

Our study revealed reduced expression (mRNA/protein) and high alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation was, however, rare in inactivation of MCPH1. In immunohistochemical analysis, reduced protein expression of MCPH1, ATM and p-ATM were concordant with their molecular alterations (P = 0.03–0.01). Alterations of MCPH1 and deletion of ATM were significantly high in estrogen/progesterone receptor–negative than estrogen/progesterone receptor–positive breast carcinoma samples compared to early or late age of onset tumors, indicating differences in pathogenesis of the molecular subtypes (P = 0.004–0.01). These genes also showed differential association with tumor stage, grade and lymph node status in different subtypes of breast carcinoma (P = 0.00001–0.01). Their coalterations showed significant association with tumor progression and prognosis (P = 0.003–0.05). Interestingly, patients with alterations of these genes or MCPH1 alone had poor outcome after treatment with DNA-interacting drugs and/or radiation (P = 0.01–0.05).

Conclusions

Inactivation of MCPH1-ATM-associated DNA damage response pathway might have an important role in the development of breast carcinoma with diagnostic, prognostic and therapeutic implications.

     

Bilateral bifid ureter with unilateral renal vasculature variations

During routine dissection of 82-year-old female cadaver with no known unfavorable medical history, we observed bilateral bifid ureter and variation in arterial supply of left kidney only. Careful examination revealed that there were bifid ureters on both sides enclosed in single facial sheath. It was also observed that both the ureter have different pattern of origin. On the right side, both the ureters were seen to be emerging from the hilum, one below another and joined together at the brim of the lesser pelvis just before crossing the right external iliac artery. Right kidney was supplied by single renal artery lying anterior to both the ureters. On the left side one ureter emerged from the hilum while the second one exited the kidney from a prominent lobule present below the inferior pole.     

Glutamate system,amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.