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Biomedical subjects

H Holloway

Publications and source records attributed to H Holloway.

At least 19 recordsLinked to original sources
PubMed2001

Detection of submicroscopic magnetite particles using reflectance mode confocal laser scanning microscopy.

Light microscopy and transmission electron microscopy work at such different scales that some components of cells may be too small to detect using light microscopy but too dispersed among cells within tissues to be discovered using electron microscopy. We have used reflectance mode confocal laser scanning microscopy to detect single-domain magnetite crystals in both live and resin-embedded preparations of magnetotactic bacteria. We show that reflections from bacterial cells are uniquely associated with the magnetite, which underpins the magnetotactic response of the bacteria. En bloc viewing shows that relatively large volumes of material can be searched with sufficient resolution to enable detection of submicroscopic particles. The techniques reported here may be of interest to others wishing to detect submicroscopic objects dispersed in large volumes of tissue.

Bacteria↗
PubMed2000

Amyloid-like inclusions in Huntington's disease.

Huntington's disease is a progressive, autosomal dominantly inherited, neurodegenerative disease that is characterized by involuntary movements (chorea), cognitive decline and psychiatric manifestations. This is one of a number of late-onset neurodegenerative disorders caused by expanded glutamine repeats, with a likely similar biochemical basis. Immunohistochemical studies on Huntington's disease tissue, using antibodies raised to the N-terminal region of huntingtin (adjacent to the repeat) and ubiquitin, have recently identified neuronal inclusions within densely stained neuronal nuclei, peri-nuclear and within dystrophic neuritic processes. However, the functional significance of inclusions is unknown. It has been suggested that the disease-causing mechanism in Huntington's disease (and the other polyglutamine disorders) is the ability of polyglutamine to undergo a conformational change that can lead to the formation of very stable anti-parallel beta-sheets; more specifically, amyloid structures. We examined, using Congo Red staining and both polarizing and confocal microscopy, post mortem human brain tissue from five Huntington's disease cases, two Alzheimer's disease cases and two normal controls. Brains from five transgenic mice (R6/2)(12) expressing exon 1 of the human huntingtin gene with expanded polyglutamine, and five littermate controls, were also examined by the same techniques. We have shown that some inclusions in Huntington's disease brain tissue possess an amyloid-like structure, suggesting parallels with other amyloid-associated diseases such as Alzheimer's and prion diseases.

Alzheimer Disease↗
PubMed1997

Small cell carcinoma of the lung presenting as chylous ascites: a unique case.

A 67-year-old female presenting with a history of weight loss and abdominal distension was noted on examination to have ascites. Paracentesis revealed a chylous ascites and chest radiography showed a right hilar enlargement with mid-zone infiltration. Abdominal computed tomography demonstrated retroperitoneal lymphadenopathy and biopsy of this showed small cell undifferentiated carcinoma. This appears to be the first documented association between metastatic small cell carcinoma of the lung and chylous ascites.

Aged↗
PubMed1996

Primary hepatic leiomyosarcoma.

Hepatomegaly was noted in a 63-year-old man who presented with an exacerbation of chronic pulmonary disease. A diagnosis of hepatic leiomyosarcoma was made by fine needle aspiration biopsy. Intensive investigations failed to reveal a primary source. The patient was treated conservatively.

Biopsy, Needle↗
PubMed1996

Colonoscopic findings in Crohn's disease--reproducible, but of questionable benefit.

Colonoscopy, a useful diagnostic tool in inflammatory bowel disease, is very accurate in detecting disease and assessing disease extent in Crohn's disease. Despite their accuracy, colonoscopic findings have not been routinely used in the objective follow-up of patients with Crohn's disease. The GETAID (Groupe d'études theraputic des affections inflammatoire du tube digestif) group has shown that following an intensive training period, endoscopists can describe colonoscopic findings in a reproducible manner. However, these descriptions poorly correlate both with clinical or laboratory indexes, and with short or medium term prognosis following prednisolone therapy.

Colonoscopy↗
PubMed1995

Pancreatic vipomas: spectrum of presentation and evolution of diagnostic and therapeutic modalities.

Two patients are reported who presented with symptoms characteristic of a pancreatic vipoma. The necessity to measure more than one plasma VIP level for diagnosis, and the delay between the onset of illness and diagnosis is illustrated by both cases. Evidence suggests that vipomas are still under reported. The evolution of sophisticated diagnostic and therapeutic modalities over the twenty-five years separating both presentations is discussed.

Combined Modality Therapy↗
PubMed1993

Administration of melanotropic peptides during gestation in the rodent.

A potent analogue of alpha-MSH (alpha-melanocyte stimulating hormone, S-alpha-melanotropin), [Nle4,D-Phe7] alpha-MSH, induces darkening of follicular melanocytes when injected or applied topically to the skin of mice [1]. This analogue also results in increased pigmentation when injected subcutaneously (s.c.) in humans. Toxicological studies have been performed on rodent models with administration topically or by intraperitoneal (i.p.) injection. No toxicity was observed and no pathological or significant biochemical changes were found. However there has been some controversy in the literature revolving around whether or not alpha-MSH is trophic for fetal growth and whether the hormone affects fetal adrenal development. These questions have been addressed in this study. All previous studies on the possible reproductive function of alpha-MSH have involved use of the natural hormone only. This is first to demonstrate the effects of the more potent analogue. The rat was used as the animal model to determine if the potent analogue of alpha-MSH affects events in gestation and embryonic fetal development and to determine if the analogue was a developmental toxicant. This study also examines the effect of a melanotropic peptide delivered directly to the conceptus in utero during organogenesis. No changes were found in the parameters examined (sex ratio, weight, morphology or histology, etc.) between treated and control fetuses. There was no evidence of premature parturition or pigmentation changes in the fetuses. The work reported in this study is of relevance if such a melanotropic peptide is to be used in women of childbearing age to induce pigmentation of the skin. Although the present results cannot necessarily be extrapolated to humans, indications are that, in rodents at least, [Nle4,D-Phe7] alpha-MSH and natural alpha-MSH have no adverse effects when administered during gestation and fetal development.

Animals↗
PubMed1991

Morphometric analyses of adrenal gland growth in fetal and neonatal sheep. III. Volumes of the major organelles within zona fasciculata steroidogenic cells.

We have undertaken a morphometric analysis of the distribution patterns of the major subcellular organelles of the zona fasciculata in fetal (53, 100, 130, 144 days) and neonatal (2 days) sheep as they may be expressed as volume densities, volumes per cell, volumes per 100 microns 3 of cytoplasm per cell, and volumes per mm3 of steroidogenic cells per gland. Data obtained indicate that certain of the volume densities and the 3 other volume indicators of the 6 organelles considered change with gestational age. While the volume of mitochondria per cell increased in late gestation because of cellular hypertrophy, the real time volumes of mitochondria per unit volume of cell or gland did not vary significantly during the period of development studied. The volume of the SER, however, changed markedly, being minimal at 100 days fetal development (0.68 gestation) and increasing, probably initially during the 123-130 day (0.84-0.88 gestation) period, until the end of the fetal period (term = 147 days). The SER exhibited the most marked variability in the three volume indicators, the volumes correlating closely with cell size and steroidogenic capability. The RER volumes altered little, decreasing per 100 microns 3 of cytoplasm from mid-gestation, probably as a reflection of the cell maturity state attained. Changes in the distribution of the Golgi apparatus paralleled those of the SER; but the lipid storage droplets were sparse and their volumes constant. In the fetal sheep, the Golgi apparatus appears to be a significant component of the steroidogenic organelle complex, while the lipid droplet compartment does not. Consideration of growth during the 2nd major growth phase of the adrenal cortex (from before 0.85 gestation), as expressed in mitotic events, showed that at 130 days (0.88 gestation) cellular replication was randomly spread through the zona fasciculata, whereas at 144 days (0.98 gestation) mitoses were twice as prevalent in the outer half of that zone as they were in the inner half. At 130 and 144 days, the cells of the outer half of the zona fasciculata contained significantly more smooth endoplasmic reticulum than did those of the inner half. The maturation of the zona fasciculata, which allows the maximal production of cortisol in late pregnancy, thus occurs in a centripetal direction. This may result from the fact that the outer cells of the zona fasciculata are first in contact with the rising levels of ACTH and cortisol, two primary determinants of its growth and differentiation during the last 3 weeks of gestation.

Animals↗
PubMed1989

Morphometric analyses of the effects of thyrotrophin releasing hormone and cortisol on the lungs of fetal sheep.

Morphometric analyses of ovine fetal lung parenchyma were undertaken in order to elucidate the roles of pituitary, thyroid and adrenocortical hormones in promoting the structural changes underlying the increased distensibility and stability present in mature fetal lungs. Twenty-six Romney fetuses were treated with either cortisol for 84 h from 125 days (4), pulsatile TRH for 6.5 days from 122 days (4), cortisol and TRH (12), or 0.9% NaCl solution (6). The left lungs were used for physiological studies (distensibility, V40) and the right lungs were prepared for electron microscopy. Using 32 regions of lung parenchyma per fetus, volume density, surface density and arithmetic mean thickness of the alveolar walls were calculated using point and intersection counts. Of the three regimens, treatment with TRH + cortisol (exposure to raised concentrations of cortisol, T3 and prolactin) induced significantly greater lung distensibility, the largest potential alveolar air space (62% of the parenchyma), the greatest alveolar surface area (113.7 mm2/mm3 x 10(-3)) and the thinnest alveolar walls (6.7 microns). We conclude that cortisol, T3 and prolactin act synergistically to promote maturational changes in the alveolar wall. While cortisol plays the major role, T3 and prolactin enhance the ability of the immature lung to respond to the cortisol.

Animals↗
PubMed1989

Morphometric analyses of adrenal gland growth in fetal and neonatal sheep. I. The adrenal cortex.

This, the first linear morphometric analysis of the epigenesis of the fetal mammalian adrenal cortex, has shown that in the fetal sheep during the latter two thirds of gestation and in the newborn lamb, there are two periods of rapid growth separated by a period of much reduced growth. The fetal ages studies were 53 days (0.36 gestation), a period when the fetal adrenal cortex is actively steroidogenic; 100 days (0.68 gestation), a period of adrenocortical quiescence; 130 days (0.88 gestation), the period of increasing responsiveness to ACTH and cortisol production; 144 days (0.98 gestation), the period of maximal adrenocortical steroidogenesis; and 2 days postpartum, when cortisol production is normally maintained. The first adrenocortical growth period extends to mid-gestation, then growth slows to 0.85 gestation when the second growth period begins. The changes between the first growth period (0.36 gestation) and the period of quiescence (0.68 gestation) are characterised by the attainment of normal adrenocortical zonation and the separation of the medulla. The rate of adrenocortical cell division slows and the zona fasciculata cells become smaller in size. The volume density of the adrenocortical blood sinusoids decreases significantly. The onset of the second growth phase is associated with the previously reported increased levels of fetal plasma ACTH at 0.85 gestation and is expressed initially as a hypertrophic response. Cellular hypertrophy increases from 0.88 gestation to 0.98 gestation and then declines over the birth period. The rate of adrenocortical cell division increases from 0.88 gestation and maintains a maximal rate from 0.98 gestation to 2 days postpartum. These interactions of cellular hypertrophy and hyperplasia, which result in adrenocortical growth, may be explained as a response to fetal ACTH, which has the ability to stimulate the production of peptide growth and differentiation factors, e.g. IGF-II, and cortisol, which then control adrenocortical development in an autocrine and paracrine fashion.

3-Hydroxysteroid Dehydrogenases↗
PubMed1989

Morphometric analyses of adrenal gland growth in fetal and neonatal sheep. II. The adrenal medulla, with some observations on its ultrastructure.

This account of fetal and neonatal sheep adrenomedullary development is the first such study in mammals using both morphometric and microscopic techniques. At 53 days gestation some cells in the migratory whorls and columns contained noradrenaline (NA) granules whereas by 100 days the medulla, now enclosed by the cortex, was composed of elongated juxtacortical cells and rounded central medullary cells, both populations of cells containing NA granules. In the 130 days glands, many of the juxtacortical cells contained adrenaline granules and had synaptic connection with axons of the preganglionic sympathetic nerve fibres. Later development was essentially growth-related. While the juxtacortical cells decreased from 33% of the medulla at 100 days to 22% at 144 days, the central medullary cells increased from 19% to 30% over the same period. Both cell populations exhibited hypertrophic growth over the study period; but the central cells multiplied at a faster rate. We conclude that the development of the cortical and medullary compartments of the adrenal gland are closely linked, for both showed rapid mid-gestational growth which slowed with the attainment of definitive tissue organisation. Then a second phase of growth, associated with increased and controlled catecholamine secretion in the medulla and cortisol secretion in the cortex, occurred in late gestation.

Adrenal Medulla↗