A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling.

In the liver, mitochondria are exposed to different concentrations of nutrients due to their spatial positioning across the periportal and pericentral axis. How the mitochondria sense and integrate these signals to respond and maintain homeostasis is not known. Here, we combine intravital microscopy, spatial proteomics, and functional assessment to investigate mitochondrial heterogeneity in the context of liver zonation. We find that periportal and pericentral mitochondria are morphologically and functionally distinct; beta-oxidation is elevated in periportal regions, while lipid synthesis is predominant in the pericentral mitochondria. In addition, comparative phosphoproteomics reveals spatially distinct patterns of mitochondrial composition and potential regulation via phosphorylation. Acute pharmacological modulation of nutrient sensing through AMPK and mTOR shifts mitochondrial phenotypes in the periportal and pericentral regions, linking nutrient gradients across the lobule and mitochondrial heterogeneity. This study highlights the role of protein phosphorylation in mitochondrial structure, function, and overall homeostasis in hepatic metabolic zonation. These findings have important implications for liver physiology and disease.

Poisoning in Jamaican children - abstract

All admissions to the Paediatric wards of the University Hospital of the West Indies for the 12-year period, February 25, 1961 to February 28, 1973, have been examined. 130 cases of poisoning or drug overdosage were admitted during this period. 101 children (78 percent) were between the ages 1 and 4 years. The yearly incidence of admissions varied from only one case in 1962 to 18 in 1971, and 60 percent of them were admitted in the latter half of the study period. Kerosene ingestion resulting in aspiration pneumonitis was the commonest cause of poisoning. Only 2 cases of salicylate poisoning were admitted - one was mildly affected while the other due to ingestion of 'oil of winter-green' was of modern severity. Phenothiazines (13 cases), acid or caustic substances (11 cases), ferrous sulphate (10 cases), barbiturates (7 cases), ackee with toxic hypoglycaemia (6 cases), digoxin (5 cases) and organic phosphate insecticides (5 cases) accounted for most of the other admissions. 2 cases of lead poisoning and 2 children with severe vomiting and diarrhoea due to ingestion of 'Physic nut' (Jatropha curcas) were admitted and there were single cases of poisoning from a variety of toxic substances including napthalene (camphor balls), oil of chenopodium and nitrobenzene. One child was admitted following an overdose of lignocaine administered in Casualty for local anaesthesia and another from linctus codeine given for diarrhoea. 5 patients died, one from severe pneumonitis. 3 from toxic hypoglycaemia and the 5th from an unknown poison. Examination of the admission records of all children admitted to the Casualty Observation ward during a 20-month period, 1971-1972, revealed 54 cases of poisoning. 37 of these were due to kerosene ingestion and only 2 of these were admitted to the ward, the others being discharged after 1 to 3 days of observation. Many milder cases of poisoning are seen in Casualty and treated and sent home without further observation (AU)

Observations on liver size in healthy Jamaican children: Hermitage survey

A survey was done of all the children up to 12 years of age in Hermitage, a Government Housing Project. The different techniques for measuring liver size are briefly discussed and reasons given for adopting the measurement of liver size in the right mid-clavicular line below the costal margin in the expiratory pause. Tables showing the average liver sizes in age groups are presented and related to the estimated protein contents of their diets. Graphs of the heights and weights of these children in age groups showed no significant difference in 3 dietary groups based on protein intake. Some unexpected findings as regards liver size are recorded (AU)

Trichiuris infestation in children

We review the case histories of 40 children with Trichiuris infestation. The presenting features are analysed, the varying age incidence is noted, and a commentary is made on the efficacy of therapy in eradicating the worm. (AU)

Familial and recurrent veno-occlusive disease of liver in Jamaican children (abstract only)

The case histories of four children in a family of seven are presented. The eldest of the four, a girl, presented in 1961 at age 4 1/2 years with evidence of liver disease and portal hypertension. A liver biopsy was not performed. This child died in 1964 of hepatorenal failure and unfortunately permission for autopsy was refused. The second affected child, a boy, presented at age 2 years with hepatosplenomegaly and jaundice and a needle biopsy of his liver revealed a histological picture consistent with post V.O.D. cirrhosis. He has remained fairly well since, although signs of cirrhosis persist. In June 1966 two female siblings age 1 year and 2 years respectively, presented at the same time with acute abdominal swelling. Liver biopsies confirmed the clinical diagnosis of acute V.O.D. and their subsequent progress is briefly reviewed. The case history of a boy who has had two proven episodes of acute V.O.D. is presented. This child was first admitted in January 1958 at age 1 year and five months, with acute abdominal swelling. A liver biopsy revealed histological evidence of acute V.O.D. His clinical condition settled and repeat biopsy in March 1958 showed no residual liver disease. He remained well after this until he had an episode of obstructive jaundice in 1960 which subsided spontaneously. In 1965 he was readmitted with a history of acute abdominal swelling and after two months during which time his ascites gradually subsided, a liver biopsy was performed and this showed subacute V.O.D. A final biopsy was done in September 1966 and this showed only minimal increase of fibrous tissue. A brief note on the aetiology of V.O.D. is submitted(AU)

Malignant hypertonic hyperpyrexia

A case of malignant hypertonic hyperpyrexia is reported, occurring in a 2 1/2 year old Chinese boy living in Jamaica. The illness progressed rapidly with a fatal outcome, in spite of active resuscitation. Aetiology, diagnosis and treatment of the condition are briefly discussed (AU)

Pathology of congenital rubella in Jamaica

The pathological features of 8 cases of congenital rubella, resulting from a recent epidemic in Jamaica, have been described. In addition to the findings reported in the recent American paediatric literature, we have found nephrocalcinosis, congenital glomerulosclerosis, cerebral dystrophic calcification, and atrophy of the rhymus. A parallel has been suggested between the congenital rubella syndrome and runt disease (AU)

The clinical estimation of neonatal jaundice in Jamaica

257 serum bilirubin determinations have been performed in neonates, born at the University College Hospital of the West Indies, and the results have been compared with the clinical degree of jaundice in each case. A fairly close correlation has been shown to exist. In 213 cases the complexion of the infant was recorded. The darker the baby the more difficult it is to assess accurately the degree of jaundice. An experienced observer may ignore mild jaundice appearing twenty-four hours or more after birth. Bilirubin determinations should be performed in all moderate or severe cases and whenever jaundice appears within twenty-four hours of birth (AU)

An outbreak of congenital rubella in Jamaica: clinical features

An epidemic of clinical rubella occurred in Jamaica in the early months of 1965 and the clinical and laboratory findings in 20 affected babies born under the care of the University College Hospital between September 1965 and January 1966 are presented. Four infants died. Eight mothers gave positive histories of rubella in the first trimester of pregnancy. In addition to the classical eye defects, congenital heart disease and intrauterine growth retardation, evidence of systemic infection, including transient bone changes, thrombocytopenia with purpura, splenomegaly, hepatomegaly, hepatitis with regurgitative jaundice, central nervous system signs and anaemia, were present in the majority of cases. The frequency of occurrence of these complications is similar to that of published reports following the 1964 epidemic of rubella in the United States. Diarrhoea and congenital peridontal cysts and teeth were recognised for the first time as being associated with intrauterine rubella infection. Virus confirmation has not yet been obtained, but a visiting nurse from Dominica developed the classical features of rubella three weeks following exposure to some of these infants (AU)

Acute glomerulonephritis in Jamaican children

The case histories of 150 children admitted to the University College Hospital with acute glomerulonephritis have ben reviewed and the clinical and laboratory findings presented. Two of these children and one other not included in this series died, and brief clinical histories and pathological details are given. An epidemic of acute glomerulonephritis occurred in Jamaica in 1964 and this was reflected by the increased number of admissions during that year. Skin sepsis was the possible aetiological factor in more than 50 per cent of these cases and was the only known antecedent cause in 30 per cent. Forty-two per cent of the patients were under five years of age on admission and the recorded incidence of severe hypertension was much lower in this group. All 8 cases who developed hypertensive encephalopathy before or after admission were over five years of age. Ninety-one per cent of the children were known to be clinically well and free of albuminuria when last seen (AU)

Cor pulmonale secondary to chronic nasopharyngeal obstruction in a child

The case history of a twenty-one month old boy who presented with congestive cardiac failure in association with chronic tonsillar and adenoidal hypertrophy is presented. This is the first such case to be reported from Jamaica. The aetiology of cardiac failure in association with upper airway obstruction is briefly discussed (AU)

Vitamin-D deficiency rickets in Jamaican children

Vitamin-D deficiency is not as rare in Jamaica as previously believed. 9 children with vitamin-D deficiency rickets have been seen at the University Hospital of the West Indies during the past 5 years. All were over 3 years of age at time of presentation. Both dietary deficiency of vitamin-D and lack of exposure to sunlight seem to be important causes. Children living in rural Jamaica seem to be more susceptible to the disease than those living in a city, due perhaps to more prolonged breast feeding and lack of fortified milk feeds on weaning.(AU)

Congenital hepatic fibrosis in Jamaican children

Clinical and pathological data are presented on 8 children with the syndrome described as congential hepatic fibrosis. The karyotypes were normal in 3 children in whom this examination was undertaken. Four also had polycystic disease of the kidneys. These studies emphasize the presence of recurrent fevers and infections and severe anaemia as being important features when the disease occurs in early childhood. Clinical portal hypertension was not seen. As in previous studies, a strong familial tendency was encountered. The exact aetiology remains obscure. (Summary)

A report on 73 consecutive cases of carcinoma of the cervix uteri seen at the University College Hospital of the West Indies: part II

Data on 73 consecutive cases of carcinoma of the cervix uteri observed in the University College Hospital are presented and the morbid anatomical and clinical features and the treatment are analysed. Amongst our patients this disease occurs 10 to 15 years earlier than in Britain and the United States of America. It is suggested that this is the result of earlier sexual activity and childbearing. The Bonney-Wertheim operation has been performed 20 times in this series with one post-operative death. There have been three recurrences over the first 2.5 years of follow-up. Additional particulars, taken from the records of other hospitals and the Registrar General, are also given for the purpose of comparison and orientation regarding some demographic data. (AU)

Adreno-genital syndrome

Three cases due to congenital adrenal hyperplasia were presented: a 33 months old girl with abnormal genitalia since birth, a male infant salt loser presented at 3 weeks of age with evidence of adreno-cortical insufficiency and a 45 year old female pseudo-hermaphrodite (AU)

Neonatal jaundice in Jamaican children

ABO incompatibility, prematurity, maternal diabetes and Rhesus incompatibility were the only significant causes of jaundice found in 400 children born at U.H.W.I. from Jan. 4 to March 6th. Glucose-6-phosphate dehydrogenase deficiency was not found to be a significant cause (AU)

A review of typhoid infection in Jamaica - abstract

During the period 1952-1959 there were two major epidemics of typhoid in Jamaica and 121 documented cases of typhoid infection were treated at the University College Hospital. Diagnosis was made mainly on culture of the organism and less reliance was placed on Widal agglutinations as T.A.B. inoculations are frequently given prophylactically in Jamaica. This disease was found to be mainly one of the young age groups. Although most cases responded to treatment, there was a relapse rate of 8 percent. Despite chloramphenicol, deaths continue to occur and a mortality rate of 5.8 percent found. The cost of treatment runs to thousands of pounds - a wasteful effort against a preventable disease (AU)

Gross cardiac involvement in glycogen storage disease type 3

This report describes a patient with type 3 glycogenosis diagnosed during life but who died suddenly at home and was found at necropsy to have gross cardiac involvement. The immediate cause of death was not apparent but could possibly have been related to the very unusual degree of cardiac involvement (AU)

Acquired pulmonary stenosis due to compression by a bronchiogenic cyst

A case of pulmonary stenosis due to extrinsic compression of the pulmonary artery and right ventricular infudibulum is reported. It is believed that this is the first such case recorded in the English literature where the cause of the compression was a bronchiogenic cyst (AU)

Electron microscopy of giardia lamblia in human jejunal biopsies

A description is given of the ultrastructure of Giardia lamblia found in three jejunal biopsies from children. The unique median body, vacuoles and cytoplasmic clefts of this protozoon are illustrated. No evidence of penetration of the trophozoite into the jejunal mucosa or deeper tissues is demonstrable.(AU)